Combined antitumor effects of TNF and G-CSF on a human medulloblastoma xenograft line

Maeda, Hitoshi; Uozumi, Tohru; Kurisu, Kaoru; Matsuoka, Takashi; Kawamoto, Keiichi; Kiya, Katsuzo; Ogasawara, Hidenori; Sakamoto, Kazuhiko; Mikami, Takashi; Monden, Shuji; Harada, Kunyu; Matsuda, Yasuhiro

doi:10.1007/bf01063769

Cited by 4 publications

(6 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TNF-alpha is down regulated in tumors like melanoma [35]. Studies have observed the cytotoxic effects of TNF-alpha on medulloblastoma [37]. Other work has found that TNF-alpha is an important factor in breast cancer promotion and survival [38].…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Sensitive detection of pathway perturbations in cancers

2012

View full text Add to dashboard Cite

BackgroundThe normal functioning of a living cell is characterized by complex interaction networks involving many different types of molecules. Associations detected between diseases and perturbations in well-defined pathways within such interaction networks have the potential to illuminate the molecular mechanisms underlying disease progression and response to treatment.ResultsIn this paper, we present a computational method that compares expression profiles of genes in cancer samples to samples from normal tissues in order to detect perturbations of pre-defined pathways in the cancer. In contrast to many previous methods, our scoring function approach explicitly takes into account the interactions between the gene products in a pathway. Moreover, we compute the sub-pathway that has the highest score, as opposed to merely computing the score for the entire pathway. We use a permutation test to assess the statistical significance of the most perturbed sub-pathway. We apply our method to 20 pathways in the Netpath database and to the Global Cancer Map of gene expression in 18 cancers. We demonstrate that our method yields more sensitive results than alternatives that do not consider interactions or measure the perturbation of a pathway as a whole. We perform a sensitivity analysis to show that our approach is robust to modest changes in the input data. Our method confirms numerous well-known connections between pathways and cancers.ConclusionsOur results indicate that integrating differential gene expression with the interaction structure in a pathway is a powerful approach for detecting links between a cancer and the pathways perturbed in it. Our results also suggest that even well-studied pathways may be perturbed only partially in any given cancer. Further analysis of cancer-specific sub-pathways may shed new light on the similarities and differences between cancers.

show abstract

Section: Resultsmentioning

confidence: 99%

“…As noted above, exogenous treatment with recombinant TNF and IL2 have had success in mitigating tumor progression in a number of diseases [37,39,40,42]. The success of these treatments illustrates that reversing pathway perturbation to a pre-cancerous state can help to restore the healthy phenotype.…”

Section: Resultsmentioning

confidence: 99%

Sensitive detection of pathway perturbations in cancers

2012

View full text Add to dashboard Cite

show abstract

“…Other correlations however, such as antitumor effects or the prevention of chemotherapy secondary effects have also been associated with the over expression of certain cytokines, especially G-CSF [29,30]. For example, Maeda H. et al, 1994, reported the antitumor effects of the combination of G-CSF and TNF on a xenograft line of human medulloblastoma [29]. Also the combination of G-CSF a key regulator of neutrophil production has been integrated to chemotherapy protocols especially for certain types of Non Hodgkin's Lymphoma[30].…”

Section: Discussionmentioning

confidence: 99%

Immunomodulatory Response Triggered by the Alkaloids, 3-Amino- 7-Benzylbenzimidazo[3,2-a] Quinolinium Chloride (ABQ-48) and 3-Nitro- 7-Benzylbenzimidazo[3,2-a] Quinolinium Chloride (NBQ-48)

Otero

Zayas

Miranda

et al. 2015

Journal of Cancer Research and Therapeutic Oncology

View full text Add to dashboard Cite

ABQ-48 (3-amino-7-benzylbenzimidazo[3,2-a]quinolinium chloride) and NBQ-48 (3-nitro-7-benzylbenzimidaw[3,2-a] quinolinium chloride) are un-natural alkaloids containing a planar heteroaromatic systems characterized by quaternized nitrogen fused to benzothiazole nucleus. Both compounds are structurally related to naturally occurring substances such as elliptine (from Ochrosia), and berberine (from Berberis). Previous in vitro studies have shown these agents to control tumor-cell proliferation indicating that both BQS are active but especially ABQ-48 at a 1 OuM dose with over 80% control of the proliferation of multiple cancer cell lines from various etiologies including colon, melanoma, CNS and ovarian cells. Mechanism of action studies have also been conducted however this is the first approach to evaluate immune modulatory activity of these novel BQS. Immune-based therapy is an increasing field in which scientists identify how the immunomodulatory activity of known and newly discovered compounds elicits an immune response that could be used against diseases. In this study, our main objective was to apply an in vitro model to show the immunomodulatory effects of ABQ-48 and NBQ-48 by analyzing the cytokine profile resulting after extracted murine spleen cells were treated with both BQS using a fluorescence-based multiplex ELISA approach. Screened cytokines included: G-CSF, GM-CSF, IL-1a, IL-2, IL-3, IL-5, IL-6, IL-7, IL-10, IL-12p70, IL-13, IL-15, IL-17, IL-21, IL-23, IFN-γ, and TNF-α. Our study results show ABQ 48 and NBQ-48 to stimulate the release of G-CSF, IL-2, IL-6, and, IFN-γ when mouse splenocytes are incubated with serial dilutions of these agents. Our finding opens new possibilities of potentially using ABQ-48 and NBQ-48 as immunomodulatory agents; with intend to activate the immune system such as the production of neutrophils against cancer or reducing chemotherapy side effects.

show abstract

“…As noted above, exogenous treatment with recombinant TNF and IL2 have had success in mitigating tumor progression in a number of diseases [2,16,27,46]. The success of these treatments illustrates that reversing pathway perturbation to a pre-cancerous state can help to restore the healthy phenotype.…”

Section: Gcm-netpath Pathway Perturbationsmentioning

confidence: 99%

“…TNF-alpha is down regulated in tumors like melanoma [31]. Studies have observed the cytotoxic effects of TNF-alpha on medulloblastoma [27]. Other work has found that TNF-alpha is an important factor in breast cancer promotion and survival [17].…”

Section: Gcm-netpath Pathway Perturbationsmentioning

confidence: 99%

Sensitive detection of pathway perturbations in cancers

Rivera

Tyler

Murali

2011

Proceedings of the 2nd ACM Conference on Bioinformatics, Computational Biology and Biomedicine

View full text Add to dashboard Cite

The normal functioning of a living cell is characterized by complex interaction networks involving many different types of molecules. Associations detected between diseases and perturbations in well-defined pathways within such interaction networks have the potential to illuminate the molecular mechanisms underlying disease progression and response to treatment. In this paper, we present a computational method that compares expression profiles of genes in cancer samples to samples from normal tissues in order to detect perturbations of pre-defined pathways in the cancer. In contrast to many previous methods, our scoring function approach explicitly takes into account the interactions between the gene products in a pathway. Moreover, we compute the sub-pathway that has the highest score, as opposed to merely computing the score for the entire pathway. We use a permutation test to assess the statistical significance of the most perturbed sub-pathway. We apply our method to 20 pathways in the Netpath database and to the Global Cancer Map of gene expression in 18 cancers. We demonstrate that our method yields more sensitive results than alternatives that do not consider interactions or measure the perturbation of a pathway as a whole. We perform a sensitivity analysis to show that our approach is robust to modest changes in the input data. Our method confirms numerous well-known connections between pathways and cancers.

show abstract

Combined antitumor effects of TNF and G-CSF on a human medulloblastoma xenograft line

Cited by 4 publications

References 22 publications

Sensitive detection of pathway perturbations in cancers

Sensitive detection of pathway perturbations in cancers

Immunomodulatory Response Triggered by the Alkaloids, 3-Amino- 7-Benzylbenzimidazo[3,2-a] Quinolinium Chloride (ABQ-48) and 3-Nitro- 7-Benzylbenzimidazo[3,2-a] Quinolinium Chloride (NBQ-48)

Sensitive detection of pathway perturbations in cancers

Contact Info

Product

Resources

About