Inhibitory effects of bovine lactoferrin on intestinal polyposis in the ApcMin mouse

Ushida, Yoshihiko; Sekine, Kazunori; Kuhara, Tetsuya; Takasuka, Nobuo; Iigo, Masaaki; Tsuda, Hiroyuki

doi:10.1016/s0304-3835(98)00249-3

Cited by 42 publications

(31 citation statements)

References 19 publications

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“…Recently, we have shown that bLF inhibits the development of AOM-induced aberrant crypt foci (precursor lesions) 9) and carcinomas 10) in the rat colon when given as 20) Furthermore, we have observed activation of NK activity in AOM-treated rats fed bLF. 8) Findings have accumulated pointing to a wide array of functions of bLF in the immune system; thus NK cell activation, 5) stimulation of LAK cell activity 6) and potentiation of macrophage cytotoxicity 7) have been documented, Many compounds have been demonstrated to exert chemopreventive effects.…”

Section: Discussionmentioning

confidence: 76%

Possible Chemopreventive Effects of Bovine Lactoferrin on Esophagus and Lung Carcinogenesis in the Rat

Ushida

Sekine

Kuhara

et al. 1999

Japanese Journal of Cancer Research

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A milk component, bovine lactoferrin (bLF), previously shown by us to be a strong chemopreventive of colon carcinoma development, was examined for its influence on other organs using a rat multi-organ carcinogenesis model. Male F344 rats, aged 6 weeks, were treated sequentially with diethylnitrosamine (DEN, i.p.), dihydroxy-di-N-propylnitrosamine (DHPN, in drinking water) and N-nitrosomethylbenzylamine (NMBA, s.c.) during the first 8 weeks (DDN treatment), and then bLF was administered in the basal diet, at a dose of 2, 0.2, 0.02 or 0.002%. Other groups were given DDN treatment or bLF alone as controls. All surviving animals were killed at week 41, and major organs were examined histopathologically for neoplastic lesions. In the esophagus, a tendency for reduction in development of papillomas was evident in the bLF-treated animals, along with a significant suppression of relatively large-sized papillomas (more than 50 mm 3 volume) at the 0.2% dose (P< < < <0.05, 11% of the control). The multiplicity of tumors (adenomas and carcinomas) in the lung was also decreased in animals fed 0.02% bLF (1.98± ± ± ±0.41 per cm 2 lung tissue section, P< < < <0.05) compared to the control group (3.48± ± ± ±0.33). No enhancing or inhibitory effects of bLF on tumor development in other organs were noted. The present results indicate that bLF exerts chemopreventive effects in the esophagus and lung in addition to the colon.

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Section: Discussionmentioning

confidence: 76%

Possible Chemopreventive Effects of Bovine Lactoferrin on Esophagus and Lung Carcinogenesis in the Rat

Ushida

Sekine

Kuhara

et al. 1999

Japanese Journal of Cancer Research

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“…APOD expression by breast carcinomas is associated with a favorable outcome, and its expression is decreased in metastatic lymph nodes; APOD is also epigenetically silenced in esophageal squamous cell carcinomas (Lamelas et al, 2000;Yamashita et al, 2002). LTF inhibits the growth of solid tumors and the development of experimental metastases in mice (Bezault et al, 1994;Ushida et al, 1998). While a comprehensive review of the literature will be impossible here, it is clear that our signature identifies a set of genes, whose involvement in the progression of human tumors can already be strongly inferred.…”

Section: Ltf and Serpinb5 Control Epithelial Cell Migrationmentioning

confidence: 99%

“…Breast tumors are most likely imprinted with metastatic ability ab initio (van de Vijver et al, 2002;van't Veer et al, 2002;Ramaswamy et al, 2003). Yet, recent molecular findings (reviewed in (Gupta and Massague, 2006)) also indicate genetically driven selection.…”

Section: How Many Metastasis Signatures?mentioning

confidence: 99%

“…The advent of post-genomic technologies has allowed direct testing of this hypothesis in human cancers. This has led to the proposal that the metastatic phenotype may be an intrinsic property of the primary tumor (the 'ab initio' theory), as supported by gene expression profile analyses of early-stage breast cancers that identified an expression signature predictive of metastasis (van de Vijver et al, 2002;van't Veer et al, 2002;Ramaswamy et al, 2003;Wang et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

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Breast cancer metastases are molecularly distinct from their primary tumors

et al. 2007

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Metastases have been widely thought to arise from rare, selected, mutation-bearing cells in the primary tumor. Recently, however, it has been proposed that breast tumors are imprinted ab initio with metastatic ability. Thus, there is a debate over whether 'phenotypic' disease progression is really associated with 'molecular' progression. We profiled 26 matched primary breast tumors and lymph node metastases and identified 270 probesets that could discriminate between the two categories. We then used an independent cohort of breast tumors (81 samples) and unmatched distant metastases (32 samples) to validate and refine this list down to a 126-probeset list. A representative subset of these genes was subjected to analysis by in situ hybridization, on a third independent cohort (57 primary breast tumors and matched lymph node metastases). This not only confirmed the expression profile data, but also allowed us to establish the cellular origin of the signals. One-third of the analysed representative genes (4 of 11) were expressed by the epithelial component. The four epithelial genes alone were able to discriminate primary breast tumors from their metastases. Finally, engineered alterations in the expression of two of the epithelial genes (SERPINB5 and LTF) modified cell motility in vitro, in accordance with a possible causal role in metastasis. Our results show that breast cancer metastases are molecularly distinct from their primary tumors.

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“…In addition, GSH is essential for the activation of T-lymphocytes and polymorphonuclear leukocytes as well as for cytokine production and successful expression of immune responses, when the host cells are immunologically challenged [36]. Besides the many possible inhibitory actions of the GSH on tumor development such as immune stimulation, and detoxication of potentical carcinogens including xenobiotics and free radicals [18], some more complex mechanisms have been proposed [20,31,32,37] for whey protein inhibition of AOM-induced intestinal ACF and colon tumor development. Bovine lactoferrin [31,32] activates natural killer (NK) cells and a positive correlation between colon tumor incidence and carcinogeninduced depression of NK activity seems to exist.…”

Section: Discussionmentioning

confidence: 99%

Dietary protein, immune function and colon carcinogenesis in the mouse

Dias

Sgarbieri

Jacobucci

et al. 2006

Lait

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-Immune stimulation and colon cancer development were studied in A/J mice injected with azoxymethane (AOM) which were maintained on undenatured whey protein concentrate (WPC), Immunocal (IM), soy protein isolate (SPI) and a commercial casein (CC) as the only source of dietary protein for 32 weeks. No difference in growth rate and body weight was found for the different treatments. Immune stimulation, after challenge by subcutaneous injection of 5 × 10 6 sheep red blood cells, was evaluated by PFC (Plaque-Forming Cells) in the spleen. Response was equal and significantly higher for WPC-and IM-fed mice, the lowest response was found for the SPI group and an intermediate response for CC. A parallel increase was observed between PFC in the spleen and glutathione concentration in the liver. Aberrant crypt foci (ACF) were confirmed as reliable markers for colon carcinogenesis and were detected by fixation in formaldehyde solution and staining with methylene blue. A high linear correlation was found between ACF and actual number of colon tumors. The most important result of this work was the significant effect of the cysteine-rich proteins in the immunological response to SRBC antigen and tumor formation. These findings confirm and extend the works reported by other investigators. protéiques suivants : concentré de protéine non-dénaturée de sérum (WPC), Immunocal (IM), isolat de protéine de soja (SPI) et caséine commerciale (CC). Aucune différence n'a été observée pour la vitesse de croissance et le poids corporel, pour les différents traitements. La stimulation immunologique, après l'injection subcutanée de 5 × 10 6 hématies de mouton, a été évaluée par la formation cellulaire de plaque (PFC) dans la rate. La réponse a été significativement plus élevée pour toutes les souris alimentées avec WPC et IM, alors que la réponse la moins élevée a été trouvée dans le groupe SPI et une réponse intermédiaire pour le groupe CC. Une augmentation parallèle a été observée entre la formation cellulaire de plaque (PFC) dans la rate et la concentration en glutathion dans le foie. L'effet des protéines riches en cystéine dans la réponse immulogique à l'antigène des hématies de moutons (SRBC) et l'inhibition de la formation des tumeurs sont les résultats les plus importants de cette étude. Ces résultats confirment et étendent les résultats des travaux publiés par d'autres chercheurs. souris / cancer du colon / azoxymethane / protéine alimentaire / immunomodulation mouse / colon cancer / azoxymethane / dietary protein / immunomodulation

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Inhibitory effects of bovine lactoferrin on intestinal polyposis in the ApcMin mouse

Cited by 42 publications

References 19 publications

Possible Chemopreventive Effects of Bovine Lactoferrin on Esophagus and Lung Carcinogenesis in the Rat

Possible Chemopreventive Effects of Bovine Lactoferrin on Esophagus and Lung Carcinogenesis in the Rat

Breast cancer metastases are molecularly distinct from their primary tumors

Dietary protein, immune function and colon carcinogenesis in the mouse

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