scholarly journals Impact of Dietary Tomato on Prostate Carcinogenesis and Progression in Lean and Overweight/Obese TRAMP Mice

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 304-304
Author(s):  
Catherine Applegate ◽  
Matt Wallig ◽  
Rita Miller ◽  
William O'Brien Jr. ◽  
John Erdman Jr.
Keyword(s):  
Body Weight ◽  
Cancer Progression ◽  
Tumor Development ◽  
Tumor Detection ◽  
Primary Objective ◽  
Tumor Incidence ◽  
Tumor Weight ◽  
Tumor Onset ◽  
Freeze Dried ◽  
Tramp Mice

Abstract Objectives The primary objective was to determine the effect of dietary tomato on prostate cancer (PCa) development and progression in overweight/obese, transgenic mice prone to PCa (TRAMP mice). Secondary objectives included assessing histological, inflammatory, angiogenic, and metabolic changes in prostate tumors at different time points of cancer progression. Methods Four-week-old TRAMP mice were randomly assigned to consume one of four diets (n = 45/diet): control (CON) or obesogenic (OB), both with and without 10% freeze-dried tomato powder (TP). Prostate tumor incidence and growth were monitored via ultrasound imaging. Mice were terminated one or four weeks following tumor development to assess early and later molecular changes in the tumors. Results OB diets led to greater body weight over time (45.2 ± 1.0 g at 24 weeks of age) when compared with CON diets (33.2 ± 0.8 g; p < 0.0001 by 2-way ANOVA), with TP inclusion having no impact on body weight within diets. OB diets resulted in greater tumor incidence (64.8% vs. 42.5%), earlier age at tumor onset (16.9 ± 1.0 weeks vs. 18.6 ± 0.7 weeks), higher body weight at tumor detection (38.6 ± 1.0 g vs. 30.8 ± 1.2 g), and greater post-mortem periprostatic adipose weight (2.0 ± 0.1 g vs. 0.9 ± 0.1 g). TP intake was protective only in lean animals, with CON-TP-fed animals having exhibited lower tumor volume at detection (28.7 ± 5.2 mm3 vs. 47.3 ± 15.5 mm3) and lower tumor weight at both one (0.1 ± 0.02 g vs. 0.2 ± 0.06 g) and four (1.5 ± 0.3 g vs. 2.1 ± 0.5 g) weeks following tumor detection compared with CON-fed animals. Conversely, TP was not protective in animals with obesity, with OB-TP-fed animals having exhibited no differences in tumor weight one week following tumor detection (0.3 ± 0.06 g vs. 0.3 ± 0.07 g) and greater tumor weight four weeks following tumor detection (2.5 ± 0.7 g vs. 2.0 ± 0.3 g) when compared with OB-fed animals. Conclusions TRAMP mice fed obesogenic diets have higher body weight and earlier onset of PCa. While tomato intake led to smaller tumors in lean animals, the opposite effect was observed in animals with higher body weight. Funding Sources This research is supported by the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health.

scholarly journals Dietary Tomato or Lycopene Do Not Reduce Castration-Resistant Prostate Cancer Progression in a Murine Model

2020 ◽  
Vol 150 (7) ◽  
pp. 1808-1817
Author(s):  
Joe L Rowles ◽  
Joshua W Smith ◽  
Catherine C Applegate ◽  
Rita J Miller ◽  
Matthew A Wallig ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
De Novo ◽  
Control Diet ◽  
Tumor Detection ◽  
Castration Resistant Prostate Cancer ◽  
Tumor Weight ◽  
Castration Resistant ◽  
Mouse Prostate ◽  
Tomato Powder ◽  
Tramp Mice

ABSTRACT Background Dietary tomato products or lycopene protect against prostate carcinogenesis, but their impact on the emergence of castration-resistant prostate cancer (CRPC) is unknown. Objective We hypothesized that tomato or lycopene products would reduce the emergence of CRPC. Methods Transgenic adenocarcinoma of the mouse prostate (TRAMP) mice were castrated at 12–13 wk and the emergence of CRPC was monitored by ultrasound in each study. In Study 1, TRAMP mice (n = 80) were weaned onto an AIN-93G-based control diet (Con-L, n = 28), a 10% tomato powder diet (TP-L, 10% lyophilized w/w, n = 26), or a control diet followed by a tomato powder diet after castration (TP-Int1, n = 26). In Study 2, TRAMP mice (n = 85) were randomized onto a control diet with placebo beadlets (Con-Int, n = 29), a tomato diet with placebo beadlets (TP-Int2, n = 29), or a control diet with lycopene beadlets (Lyc-Int, n = 27) following castration (aged 12 wk). Tumor incidence and growth were monitored by ultrasound beginning at an age of 10 wk. Mice were euthanized 4 wk after tumor detection or aged 30 wk if no tumor was detected. Tissue weights were compared by ANOVA followed by Dunnett's test. Tumor volumes were compared using generalized linear mixed model regression. Results Ultrasound estimates for the in vivo tumor volume were strongly correlated with tumor weight at necropsy (R2 = 0.75 and 0.94, P <0.001 for both Studies 1 and 2, respectively). Dietary treatments after castration did not significantly impact cancer incidence, time to tumor detection, or final tumor weight. Conclusions In contrast to studies of de novo carcinogenesis in multiple preclinical models, tomato components had no significant impact on the emergence of CRPC in the TRAMP model. It is possible that specific mutant subclones of prostate cancer may continue to show some antiproliferative response to tomato components, but further studies are needed to confirm this.

scholarly journals Black Lentil Aqueous Extract Attenuates Colitis-Associated Colon Carcinogenesis in Mice (OR04-06-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Elvira Gonzalez de Mejia ◽  
Candice Mazewski ◽  
Diego Luna-Vital ◽  
Mark Berhow
Keyword(s):  
Body Weight ◽  
Disease Control ◽  
Aqueous Extract ◽  
Activity Index ◽  
Tumor Development ◽  
Disease Activity Index ◽  
Spleen Weight ◽  
Immune Markers ◽  
Dry Extract ◽  
Freeze Dried

Abstract Objectives The objective was to compare the efficacy of a black lentil aqueous extract (BL) and a semi-purified anthocyanin (ANC) extract to prevent tumor development and inflammatory processes and impact on immune response in an azoxymethane (AOM)/dextran sodium sulfate (DSS) mouse model. Methods BL was obtained from an overnight soak of organic beluga black lentils (1:2 w/v) in water, filtered, frozen, and freeze-dried. The major ANC identified was delphinidin 3-O-(2-O-β-d-glucopyranosyl-α-l-arabinopyranoside (D3G). Seven and a half week old C57BL/6 mice were randomly separated into four groups: healthy control (n = 6), disease control (n = 14), BL (n = 12), and D3G (n = 12). After a one week acclimation, the mice were given treatments for 11 weeks, either placebo or BL: 600 or D3G: 41 mg/kg body weight (equivalent to D3G in a BL extract) using a voluntary jelly administration every morning throughout the study. Following the first week of treatments, mice received an AOM injection of 10 mg/kg body weight. Three cycles of DSS in water started one week later. The first cycle had 2% DSS for one week; the second and third cycles had 1%. Each cycle had two weeks of regular water post-DSS. Inflammation, progression, and immune markers were analyzed in the colon, spleen, and plasma by histology, gene expression, ELISA, and protein arrays. Results BL had total ANC concentration of 21.3 mg D3G equivalent/g dry extract and total polyphenol concentration of 264.9 mg gallic acid equivalent/g dry extract. BL group had a lower disease activity index (DAI), throughout and at the end, of 2.4 compared to 6.3 of the disease control and 4.0 of D3G group (P < 0.05). Mice in the BL group had an average of 7.8 neoplasms while the disease control had 12.8 and D3G had 12.1 (P < 0.05). BL group had a lower relative spleen weight and colon weight to length at 5 and 59 mg/cm compared to 10 and 82 mg/cm and 10 and 83 mg/cm of the disease control and D3G groups, respectively (P < 0.05). Based on colon cancer cell results, BL lowered expression of inhibitory immune markers, like PD-L1 (P < 0.05). Conclusions BL attenuated the DAI and helped mice maintain their weight throughout the AOM/DSS treatment. BL also resulted in a lower total and lower large neoplasm number, relative lower spleen weight, and colon weight to length ratio compared to the disease control. BL showed anti-carcinogenic anti-inflammatory properties. Funding Sources USDA-NIFA-HATCH project 1014457.

scholarly journals Growth and Progression of TRAMP Prostate Tumors in Relationship to Diet and Obesity

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Melissa J. L. Bonorden ◽  
Michael E. Grossmann ◽  
Sarah A. Ewing ◽  
Olga P. Rogozina ◽  
Amitabha Ray ◽  
...  
Keyword(s):  
Body Weight ◽  
High Fat Diet ◽  
Weight Status ◽  
Tumor Development ◽  
Tumor Detection ◽  
High Fat ◽  
Low Fat ◽  
Gold Thioglucose ◽  
Body Weight Status ◽  
Prostate Cancer Development

To clarify effects of diet and body weight on prostate cancer development, three studies were undertaken using the TRAMP mouse model of this disease. In the first experiment, obesity was induced by injection of gold thioglucose (GTG). Age of prostate tumor detection (~33 wk) and death (~43 wk) was not significantly different among the groups. In the second study, TRAMP-C2 cells were injected into syngeneic C57BL6 mice and tumor progression was evaluated in mice fed either high-fat or low-fat diets. The high fat fed mice had larger tumors than did the low-fat fed mice. In the third study, tumor development was followed in TRAMP mice fed a high fat diet from 6 weeks of age. There were no significant effects of body weight status or diet on tumor development among the groups. When the tumors were examined for the neuroendocrine marker synaptophysin, there was no correlation with either body weight or diet. However, there was a significant correlation of the expression of synaptophysin with earlier age to tumor detection and death. In summary, TRAMP-C2 cells grew faster when the mice were fed a high-fat diet. Further synaptophysin may be a marker of poor prognosis independent of weight and diet.

Interrupting the FGF19-FGFR4 Axis to Therapeutically Disrupt Cancer Progression

2018 ◽  
Vol 19 (1) ◽  
pp. 17-25 ◽  
Author(s):  
Liwei Lang ◽  
Austin Y. Shull ◽  
Yong Teng
Keyword(s):  
Cancer Progression ◽  
Therapeutic Strategy ◽  
Tumor Development ◽  
Vital Role ◽  
Signaling Cascades ◽  
Cancer Cell Proliferation ◽  
Clinical Use ◽  
Fibroblast Growth ◽  
Apoptosis Resistance ◽  
Downstream Signaling

Coordination between the amplification of the fibroblast growth factor FGF19, overexpression of its corresponding receptor FGFR4, and hyperactivation of the downstream transmembrane enzyme &#946;-klotho has been found to play pivotal roles in mediating tumor development and progression. Aberrant FGF19-FGFR4 signaling has been implicated in driving specific tumorigenic events including cancer cell proliferation, apoptosis resistance, and metastasis by activating a myriad of downstream signaling cascades. As an attractive target, several strategies implemented to disrupt the FGF19-FGFR4 axis have been developed in recent years, and FGF19-FGFR4 binding inhibitors are being intensely evaluated for their clinical use in treating FGF19-FGFR4 implicated cancers. Based on the established work, this review aims to detail how the FGF19-FGFR4 signaling pathway plays a vital role in cancer progression and why disrupting communication between FGF19 and FGFR4 serves as a promising therapeutic strategy for disrupting cancer progression.

scholarly journals LAT1 and ASCT2 Related microRNAs as Potential New Therapeutic Agents against Colorectal Cancer Progression

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 195
Author(s):  
Francisca Dias ◽  
Cristina Almeida ◽  
Ana Luísa Teixeira ◽  
Mariana Morais ◽  
Rui Medeiros
Keyword(s):  
Colorectal Cancer ◽  
Amino Acid ◽  
Cancer Progression ◽  
Cell Metabolism ◽  
Tumor Development ◽  
Amino Acid Transporters ◽  
Epigenetic Alterations ◽  
Therapeutic Approaches ◽  
Colorectal Cancer Progression ◽  
Made In

The development and progression of colorectal cancer (CRC) have been associated with genetic and epigenetic alterations and more recently with changes in cell metabolism. Amino acid transporters are key players in tumor development, and it is described that tumor cells upregulate some AA transporters in order to support the increased amino acid (AA) intake to sustain the tumor additional needs for tumor growth and proliferation through the activation of several signaling pathways. LAT1 and ASCT2 are two AA transporters involved in the regulation of the mTOR pathway that has been reported as upregulated in CRC. Some attempts have been made in order to develop therapeutic approaches to target these AA transporters, however none have reached the clinical setting so far. MiRNA-based therapies have been gaining increasing attention from pharmaceutical companies and now several miRNA-based drugs are currently in clinical trials with promising results. In this review we combine a bioinformatic approach with a literature review in order to identify a miRNA profile with the potential to target both LAT1 and ASCT2 with potential to be used as a therapeutic approach against CRC.

scholarly journals Blood Vessels and Peripheral Nerves as Key Players in Cancer Progression and Therapy Resistance

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4471
Author(s):  
Niccolò Roda ◽  
Giada Blandano ◽  
Pier Giuseppe Pelicci
Keyword(s):  
Cancer Cells ◽  
Blood Vessels ◽  
Cancer Progression ◽  
Peripheral Nerves ◽  
Tumor Development ◽  
Therapy Resistance ◽  
Tumor Mass ◽  
Cancer Pathogenesis ◽  
Initial Results ◽  
Metastatic Spreading

Cancer cells continuously interact with the tumor microenvironment (TME), a heterogeneous milieu that surrounds the tumor mass and impinges on its phenotype. Among the components of the TME, blood vessels and peripheral nerves have been extensively studied in recent years for their prominent role in tumor development from tumor initiation. Cancer cells were shown to actively promote their own vascularization and innervation through the processes of angiogenesis and axonogenesis. Indeed, sprouting vessels and axons deliver several factors needed by cancer cells to survive and proliferate, including nutrients, oxygen, and growth signals, to the expanding tumor mass. Nerves and vessels are also fundamental for the process of metastatic spreading, as they provide both the pro-metastatic signals to the tumor and the scaffold through which cancer cells can reach distant organs. Not surprisingly, continuously growing attention is devoted to the development of therapies specifically targeting these structures, with promising initial results. In this review, we summarize the latest evidence that supports the importance of blood vessels and peripheral nerves in cancer pathogenesis, therapy resistance, and innovative treatments.

scholarly journals Antibody-based antiangiogenic and antilymphangiogenic therapies to prevent tumor growth and progression.

2013 ◽  
Vol 60 (3) ◽  
Author(s):  
Monika Bzowska ◽  
Renata Mężyk-Kopeć ◽  
Tomasz Próchnicki ◽  
Małgorzata Kulesza ◽  
Tomasz Klaus ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Tumor Development ◽  
Lymphatic Vessels ◽  
Therapeutic Agents ◽  
Signaling Networks ◽  
Therapeutic Effects ◽  
Combined Treatments ◽  
Tumor Drug Resistance ◽  
Prevent Tumor Growth

Blood and lymphatic vessel formation is an indispensable factor for cancer progression and metastasis. Therefore, various strategies designed to block angiogenesis and lymphangiogenesis are being investigated in the hope to arrest and reverse tumor development. Monoclonal antibodies, owing to their unequalled diversity and specificity, might be applied to selectively inhibit the pathways that cancer cells utilize to build up a network of blood vessels and lymphatics. Among the possible targets of antibody-based therapies are proangiogenic and prolymphangiogenic growth factors from the VEGF family and the receptors to which they bind (VEGFRs). Here, we present molecular mechanisms of angiogenesis and lymphangiogenesis exploited by tumors to progress and metastasise, with examples of antibody-based therapeutic agents directed at interfering with these processes. The expanding knowledge of vascular biology helps to explain some of the problems encountered in such therapies, that arise due to the redundancy in signaling networks controlling the formation of blood and lymphatic vessels, and lead to tumor drug resistance. Nonetheless, combined treatments and treatments focused on newly discovered proangiogenic and prolymphangiogenic factors give hope that more prominent therapeutic effects might be achieved in the future.

scholarly journals Effect of Sodium Carboxymethylcellulose and Sorbitol on Anti-Peptic Ulcer Activity of Anredera cordifolia Leaves Extract

2019 ◽  
Vol 4 (1) ◽  
pp. 16
Author(s):  
Maria Ulfah ◽  
Revika Rachmaniar ◽  
Egi MR. Sudrajat ◽  
Rida W. Fadla ◽  
Hary S. Pinuji
Keyword(s):  
Body Weight ◽  
Peptic Ulcer ◽  
Normal Control ◽  
Wistar Rat ◽  
Positive Control ◽  
Negative Control ◽  
Sodium Carboxymethylcellulose ◽  
Freeze Dried ◽  
Male Wistar Rats ◽  
Negative Controls

Anredera cordifolia or binahong is one of the Indonesian medicinal plants that is used to treat peptic ulcer. The purpose of this study was to evaluate the effect of the addition of sodium carboxymethylcellulose (CMC) and sorbitol on anti-peptic ulcer activity of A. cordifolia leaves extracts in male Wistar rats. The plants were extracted using decoction method and freeze dried. Three liquid formulas were used i.e., i) a combination of sodium CMC and sorbitol; ii) only sorbitol; iii) extract only. The rats were divided into 6 groups, i.e., positive control (sucralfate 35 mg/kg body weight); negative control (80% ethanol); normal control; and 3 formulas. After the administration of the liquid formula, all groups, except normal control, were given 80% ethanol (l5 ml/kg body weight) to induce peptic ulcer. Antipeptic ulcer activity was evaluated using direct observation on rats gastric mucosa, and histopathology assessment. The result showed that the strongest anti-peptic ulcer  was shown by sorbitol only (96.95% inhibition),  followed by the combination of sodium CMC and sorbitol (92.68% inhibition). The formula which only contained extract showed only  31.70% inhibition.  Statistical analysis showed significant differences between formula 1 and 2 with negative controls. In conclusion, A. cordifolia leaves extract with the addition of sorbitol showed the strongest anti-peptic ulcer activity. Keyword: Anredera cordifolia, peptic ulcer, suspense, Wistar rat.

scholarly journals Pharmacokinetics of Telavancin at Fixed Doses in Normal-Body-Weight and Obese (Classes I, II, and III) Adult Subjects

2018 ◽  
Vol 62 (4) ◽  
Author(s):  
Kristen L. Bunnell ◽  
Manjunath P. Pai ◽  
Monica Sikka ◽  
Susan C. Bleasdale ◽  
Eric Wenzler ◽  
...  
Keyword(s):  
Body Weight ◽  
Time Profile ◽  
Primary Objective ◽  
Fixed Dose ◽  
Target Area ◽  
Obese Patients ◽  
Time Curve ◽  
Content Type ◽  
Time Zero ◽  
Concentration Time

ABSTRACT A recommended total-body-weight (TBW) dosing strategy for telavancin may not be optimal in obese patients. The primary objective of this study was to characterize and compare the pharmacokinetics (PK) of telavancin across four body size groups: normal to overweight and obese classes I, II, and III. Healthy adult subjects ( n = 32) received a single, weight-stratified, fixed dose of 500 mg ( n = 4), 750 mg ( n = 8), or 1,000 mg ( n = 20) of telavancin. Noncompartmental PK analyses revealed that subjects with a body mass index (BMI) of ≥40 kg/m 2 had a higher volume of distribution (16.24 ± 2.7 liters) than subjects with a BMI of <30 kg/m 2 (11.71 ± 2.6 liters). The observed area under the concentration-time curve from time zero to infinity (AUC 0–∞ ) ranged from 338.1 to 867.3 mg · h/liter, with the lowest exposures being in subjects who received 500 mg. AUC 0–∞ values were similar among obese subjects who received 1,000 mg. A two-compartment population PK model best described the plasma concentration-time profile of telavancin when adjusted body weight (ABW) was included as a predictive covariate. Fixed doses of 750 mg and 1,000 mg had similar target attainment probabilities for efficacy as doses of 10 mg/kg of body weight based on ABW and TBW, respectively. However, the probability of achieving a target area under the concentration-time curve from time zero to 24 h of ≥763 mg · h/liter in association with acute kidney injury was highest (19.7%) with TBW-simulated dosing and lowest (0.4%) at the 750-mg dose. These results suggest that a fixed dose of 750 mg is a safe and effective alternative to telavancin doses based on TBW or ABW for the treatment of obese patients with normal renal function and Staphylococcus aureus infections. (This study has been registered at ClinicalTrials.gov under identifier NCT02753855.)

scholarly journals The Impact of Diet on the Involvement of Non-Coding RNAs, Extracellular Vesicles, and Gut Microbiome-Virome in Colorectal Cancer Initiation and Progression

2020 ◽  
Vol 10 ◽  
Author(s):  
Bene A. Ekine-Afolabi ◽  
Anoka A. Njan ◽  
Solomon O. Rotimi ◽  
Anu R. I. ◽  
Attia M. Elbehi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Progression ◽  
Dna Methyltransferase ◽  
Molecular Mechanisms ◽  
Cell Communication ◽  
Extracellular Vesicle ◽  
Dietary Factors ◽  
Tumor Onset ◽  
Non Coding Rnas ◽  
The Impact

Cancer is the major cause of morbidity and mortality in the world today. The third most common cancer and which is most diet related is colorectal cancer (CRC). Although there is complexity and limited understanding in the link between diet and CRC, the advancement in research methods have demonstrated the involvement of non-coding RNAs (ncRNAs) as key regulators of gene expression. MicroRNAs (miRNAs) which are a class of ncRNAs are key players in cancer related pathways in the context of dietary modulation. The involvement of ncRNA in cancer progression has recently been clarified throughout the last decade. ncRNAs are involved in biological processes relating to tumor onset and progression. The advances in research have given insights into cell to cell communication, by highlighting the pivotal involvement of extracellular vesicle (EV) associated-ncRNAs in tumorigenesis. The abundance and stability of EV associated ncRNAs act as a new diagnostic and therapeutic target for cancer. The understanding of the deranging of these molecules in cancer can give access to modulating the expression of the ncRNAs, thereby influencing the cancer phenotype. Food derived exosomes/vesicles (FDE) are gaining interest in the implication of exosomes in cell-cell communication with little or no understanding to date on the role FDE plays. There are resident microbiota in the colon; to which the imbalance in the normal intestinal occurrence leads to chronic inflammation and the production of carcinogenic metabolites that lead to neoplasm. Limited studies have shown the implication of various types of microbiome in CRC incidence, without particular emphasis on fungi and protozoa. This review discusses important dietary factors in relation to the expression of EV-associated ncRNAs in CRC, the impact of diet on the colon ecosystem with particular emphasis on molecular mechanisms of interactions in the ecosystem, the influence of homeostasis regulators such as glutathione, and its conjugating enzyme-glutathione S-transferase (GST) polymorphism on intestinal ecosystem, oxidative stress response, and its relationship to DNA adduct fighting enzyme-0-6-methylguanine-DNA methyltransferase. The understanding of the molecular mechanisms and interaction in the intestinal ecosystem will inform on the diagnostic, preventive and prognosis as well as treatment of CRC.

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