Determination of dose dependence in repeated dose toxicity studies when mid-dose alone is insignificant

Kobayashi, Kazuo; Pillai, K. Sadasivan; Michael, Mathews; Cherian, Kotturathu Mammen; Araki, Akihiro; Hirose, Akihiko

doi:10.2131/jts.37.255

Cited by 3 publications

(2 citation statements)

References 12 publications

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“…40 Second, the Williams test allows statements about a global trend and its pattern, but not about the effect of each particular dose compared to NC. 41 Again, the Dunnett's test is suitable here. Third, if downturn effects occur with high dosesand this is possible due to the overdosing tendency in toxicologythe Williams' test may be problematic, i.e.…”

Section: Trend Testsmentioning

confidence: 99%

Statistical evaluation of toxicological bioassays – a review

Hothorn

2014

Toxicol. Res.

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The basic conclusions in almost all reports on new drug applications and in all publications in toxicology are based on statistical methods. However, serious contradictions exist in practice: designs with small samples sizes but use of asymptotic methods (i.e. constructed for larger sample sizes), statistically significant findings without biological relevance (and vice versa), proof of hazard vs. proof of safety, testing (e.g. no observed effect level) vs. estimation (e.g. benchmark dose), available statistical theory vs. related userfriendly software. In this review the biostatistical developments since about the year 2000 onwards are discussed, mainly structured for repeated-dose studies, mutagenicity, carcinogenicity, reproductive and ecotoxicological assays. A critical discussion is included on the unnecessarily conservative evaluation proposed in guidelines, the inadequate but almost always used proof of hazard approach, and the limitation of data-dependent decision-tree approaches.

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Section: Trend Testsmentioning

confidence: 99%

Statistical evaluation of toxicological bioassays – a review

Hothorn

2014

Toxicol. Res.

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“…Pearson correlation was used to determine linear relation between two parameters, the co-efficient of determination ( r 2 ) indicates the portion of the variation in one parameter that may be attributed to the other parameter. Dose-dependency between groups received treatments of different concentrations was tested using the nonparametric Jonckheere-Terpstra test following a significant one-way ANOVA and post-hoc multiple comparisons with Dunnett correction, as recommended [ 28 ]. A p value of less than 0.05 was considered statistically significant.…”

Section: Methodsmentioning

confidence: 99%

PAUF Induces Migration of Human Pancreatic Cancer Cells Exclusively via the TLR4/MyD88/NF-κB Signaling Pathway

Youn

Feng²,

Won³

et al. 2022

IJMS

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PAUF, a tumor-promoting protein secreted by cancer cells, exerts paracrine effects on immune cells through TLR4 receptors expressed on immune cell surfaces. This study aimed to investigate if PAUF elicits autocrine effects on pancreatic cancer (PC) cells through TLR4, a receptor that is overexpressed on PC cells. In this study, TLR4 expression was detected in PC cells only, but not normal pancreatic cells. The migration of TLR4 high-expressing PC cells (i.e., BxPC-3) was reduced by a selective TLR4 inhibitor, in a dose-dependent manner. Using TLR4 overexpressed and knockout PC cell lines, we observed direct PAUF-TLR4 binding on the PC cell surfaces, and that PAUF-induced cancer migration may be mediated exclusively through the TLR4 receptor. Further experiments showed that PAUF signaling was passed down through the TLR4/MyD88 pathway without the involvement of the TLR4/TRIF pathway. TLR4 knockout also downregulated PC membrane PD-L1 expression, which was not influenced by PAUF. To the best of our knowledge, TLR4 is the first receptor identified on cancer cells that mediates PAUF’s migration-promoting effect. The results of this study enhanced our understanding of the mechanism of PAUF-induced tumor-promoting effects and suggests that TLR4 expression on cancer cells may be an important biomarker for anti-PAUF treatment.

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- Further methods

2016

Statistics in Toxicology Using R

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Determination of dose dependence in repeated dose toxicity studies when mid-dose alone is insignificant

Cited by 3 publications

References 12 publications

Statistical evaluation of toxicological bioassays – a review

Statistical evaluation of toxicological bioassays – a review

PAUF Induces Migration of Human Pancreatic Cancer Cells Exclusively via the TLR4/MyD88/NF-κB Signaling Pathway

- Further methods

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