&lt;p&gt;Effects of Nicotinamide on Cervical Cancer-Derived Fibroblasts: Evidence for Therapeutic Potential&lt;/p&gt;

Hassan, Reem N; Luo, Hualei

doi:10.2147/cmar.s229395

Cited by 4 publications

(3 citation statements)

References 35 publications

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“…Interestingly, even though the experimental proteomics data was not phase specific, we observed the highest overlap for nicotinamide targets with CAROM predictions in the G2 phase of the cell cycle (hyper-geometric p-value = 3 x 10 -16 ), which also had the highest number of acetylated reactions (Figure 3E; S. Table 14). This overlap suggests that growth inhibition likely occurs in the G2 phase, which is consistent with experimental data from nicotinamide treatment in various mammalian cell types that have observed growth arrest at G2 [58][59][60]. Within the table, the number of overlapping genes between each phase and drug is shown, along with the p-value of the hypergeometric test.…”

Section: Classifying Metabolic Regulation By Ptms Using Caromsupporting

confidence: 80%

Metabolic signatures of regulation by phosphorylation and acetylation

Smith

Shen

Lee

et al. 2019

Preprint

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8The metabolism of most organisms is controlled by a diverse cast of regulatory processes, including 9transcriptional regulation and post-translational modifications (PTMs). Yet how metabolic control is 10 distributed between these regulatory processes is unknown. Here we present Comparative Analysis of 11Regulators of Metabolism (CAROM), an approach that compares regulators based on network 12 connectivity, flux, and essentiality of their reaction targets. Using CAROM, we analyze transcriptome, 13proteome, acetylome and phospho-proteome dynamics during transition to stationary phase in E. coli 14 and S. cerevisiae. CAROM uncovered that the targets of each regulatory process shared unique 15 metabolic properties: growth-limiting reactions were regulated by acetylation, while isozymes and futile-16 cycles were preferentially regulated by phosphorylation. Reversibility, essentiality, and molecular-17weight further distinguished reactions controlled through diverse mechanisms. While every enzyme can 18 be potentially regulated by multiple mechanisms, analysis of context-specific datasets reveals a 19 conserved partitioning of metabolic regulation based on reaction attributes. 20Author summary 21There are several ways to regulate an enzyme's activity in a cell. Yet, the design principles that 22determine when an enzyme is regulated by transcription, translation or post-translational modifications 23 are unknown. Each control mechanism, such as transcription, comprises several regulators that control 24 a distinct set of targets. So far, it is unclear if similar partitioning of targets occurs at a higher level, 25between different control mechanisms. Here we systematically analyze patterns of metabolic regulation 26 in model microbes. We find that five key parameters can distinguish the targets of each mechanism. 27These key parameters provide insights on specific roles played by each mechanism in determining 28 overall metabolic activity. This approach may help define the basic regulatory architecture of metabolic 29 networks. 30

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Section: Classifying Metabolic Regulation By Ptms Using Caromsupporting

confidence: 80%

Metabolic signatures of regulation by phosphorylation and acetylation

Smith

Shen

Lee

et al. 2019

Preprint

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“…HPV-related cancer such as cervical cancer is a spectrum disease with a gradual progression from pre-malignant condition to aggressive disease, which begins in the cervix, and later spreads towards the lower uterine segment, vagina, para-cervical space, along with the broad and uterosacral ligaments. 47 Among patients with cervical cancer, approximately 4.16%–7.7% develop lung metastasis, 0.8%–23% develop bone metastases, and the overall outcome of patients with metastatic cervical cancer is poor. 48 Thus, we evaluated indicators related to cervical cancer invasion and metastasis, including MMP-2, MMP-9, and α-SMA and their correlated expression with the different administration route of the vaccine.…”

Section: Discussionmentioning

confidence: 99%

Intratumoral Injection of a Human Papillomavirus Therapeutic Vaccine-Induced Strong Anti-TC-1-Grafted Tumor Activity in Mice

Che¹,

Yang²,

Suo³

et al. 2021

CMAR

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Purpose The route of administration of a therapeutic tumor vaccine is a critical factor in inducing antitumor activity. In this study, we explored the effects of three vaccination routes (subcutaneous, peritumoral, and intratumoral injection) on antitumor activity induced by a human papillomavirus (HPV) therapeutic vaccine containing HPV16 E7 peptide combined with the adjuvant CpG ODN in established TC-1 grafted tumors. Methods We used flow cytometry to evaluate splenic and tumor-infiltrating immune cells. We also assessed transcriptional changes in a sequence of immune-related genes in tumors of different treatment groups using quantitative real-time polymerase chain reaction. Immunohistochemistry was used to determine the expression of molecules related to tumor infiltrating immune cells, angiogenesis, and cancer-associated fibroblasts in tumor tissues. Results Our results suggested that intratumoral and peritumoral vaccination generated enhanced antitumor activity compared to subcutaneous delivery. In particular, intratumoral vaccination elicited a stronger antitumor effect, with two of the six treated mice being nearly tumor-free at day 28. Three vaccination routes induced increases in splenic CD4+ and/or CD8+ T lymphocytes, and marked decreases in immunosuppressive cells. Peritumoral vaccination increased the tumor-infiltrating CD8+T cells in tumors, while intratumoral vaccination enhanced the tumor-infiltrating CD4+ and CD8+ T lymphocytes, as well as decreased the tumor-infiltrating of immunosuppressive cells, which may result in stronger inhibition of tumor growth and prolonged survival in mice bearing tumors. Furthermore, compared to the subcutaneous route, intratumoral vaccination led to a significant increase in antitumor cytokines and chemokines. In addition, our data showed marked downregulation of MMP-2, MMP-9, VEGF, CD31, and α-SMA in the intratumoral vaccination group, which might contribute to the suppression of tumor invasion, angiogenesis, and metastasis. Conclusion Overall, intratumoral vaccination is superior to subcutaneous delivery and has the potential to inhibit tumor growth by improving the tumor microenvironment.

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“…vitamin B3, endogenous metabolite) plays a major role in the metabolic pathway for production of nicotinamide adenine dinucleotide (NAD + ) (Gasperi et al, 2019[ 10 ]). NAM further was found to arrest the cancer microenvironment by suppression of cancer associated fibroblasts (CAF) proliferation through increasing the cellular oxidative stress in vitro (Hassan et al, 2020[ 14 ]). Adenine is a purine derivative synthesized in human liver and also found in brewer's yeast and vegetables (Lai et al, 2019[ 21 ]) and detected in P. juliflora .…”

Section: Discussionmentioning

confidence: 99%