A novel human tumor necrosis factor alfa mutein, F4614, inhibits in vitro and in vivo growth of murine and human hepatoma: Implication for immunotherapy of human hepatocellular carcinoma

Atarashi, Yoshinari; Yasumura, Satoshi; Nambu, Shuji; Yoshio, Yukimatsu; Murakami, Jun; Takahara, Taro; Higuchi, Kenichi; Watanabe, Akïharu; Miyata, Keizo; Kato, Masanari

doi:10.1002/hep.510280110

Cited by 10 publications

(6 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Wt hTNF and F4614 (5 µg/mouse daily for 5 days) showed similar anti-tumor activities in syngeneic MH134-bearing mice and heterogeneic PLC/PRF/5-bearing athymic nude mice [71]. However, in view of the previously reported significant differences in pharmacokinetics of hTNF in mice, as compared to mTNF, these results cannot necessarily be extrapolated to the human system.…”

Section: Tnf Mutants With Reduced Systemic Toxicitymentioning

confidence: 90%

Tumor Necrosis Factor: How to Make a Killer Molecule Tumor-Specific?

Lucas¹,

Kresse²,

Latta³

et al. 2005

CCDT

View full text Add to dashboard Cite

The interest in TNF, discovered at the interface between inflammation and cancer, as an anti-cancer agent, has phased out in recent years. Indeed, despite its profound cytostatic and cytotoxic effects in primary tumors, the cytokine's systemic toxicity in general and its hepatotoxic and pro-metastatic nature in particular, prevent its routine use in cancer patients. An elegant approach to circumvent these problems consists in the local application of TNF in an isolated limb or organ setting, preferentially in the presence of cytostatic and alkylating agents, such as melphalan. However, this treatment, when locally applied during the perfusion of liver tumors, results in hepatotoxicity in a significant number of the patients, by means of a still unknown mechanism. The hemorrhagic necrosis of the tumors induced by TNF seems to be predominantly mediated by an induction of apoptosis as well as by an anti-angiogenic effect in the endothelial cells of the microvasculature supplying the tumor. These cells therefore represent a prime target for the action of anti-cancer drugs. In this review, we discuss preclinical studies which elucidated the mechanism of melphalan- and TNF-associated hepatotoxicity and, as a consequence, provided insights for preventing the adverse reactions of the drug. Moreover, we review recent findings aimed at improving the TNF molecule by means of specific mutations, or searching for alternative factors lacking the systemic toxicity of TNF.

show abstract

Section: Tnf Mutants With Reduced Systemic Toxicitymentioning

confidence: 90%

Tumor Necrosis Factor: How to Make a Killer Molecule Tumor-Specific?

Lucas¹,

Kresse²,

Latta³

et al. 2005

CCDT

View full text Add to dashboard Cite

show abstract

“…Mild-to-moderate iron overload is a common finding among patients with chronic HCV infection; indeed, up to 30 -40 % of them may show increased serum transferrin-iron saturation and serum ferittin or increased hepatic iron concentration [2,3]. Elevated iron indices have been correlated with a progression of the liver disease and a decreased response to antiviral therapy [4][5][6][7][8][9]. Excess iron increases the formation of reactive oxygen species leading to lipid peroxidation, damage to protein and DNA, and thereby to cell membranes and genomic damage.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of serum iron and ferritin in different treatment regimens for chronic hepatitis C virus

Bazeed¹,

Elsayed²,

El-Aziz³

2016

IOSR

View full text Add to dashboard Cite

This work aims to develop a biochemical study on the effect of both interferon containing treatment regimens and interferon free regimens on serum iron and serum ferritin in patients with chronic hepatitis C and to evaluate the role of iron in the severity and course of disease. Blood samples from one hundred fifty patients aged from 25 to 57 years old were withdrawn; of them 30 blood samples were positive for HCV antibodies and negative for HCV RNA (control group I) and 120 blood samples were positive for HCV antibodies and positive for HCV RNA (diseased group II) which is subdivided into four groups according to the received treatment; interferon and ribavirin (group IIa), interferon, sofosbuvir and ribavirin (group IIb), sofosbuvir and ribavirin (group IIc) and herbal therapy (group IId). After treatment there was an extremely significant decrease in iron levels (94 ± 16.96 µg/dL) in group IIa, , while there was an extremely significant increase in iron levels after treatment in group IIb and group IIc (160.4 ± 37.53 µg/dL and 183.7 ± 37.36 µg/dL), respectively. Group IId showed a non significant decrease in iron levels after treatment (150.5 ± 21.35 µg/dL). For ferritin levels, group IIa, group IIb and group IIc showed significant increase in serum ferritin levels after treatment (157.6 ± 13.44, 99.5 ±14.99, and 96.63 ± 15.22 ng/mL), respectively. On the other hand, group IId showed a non significant increase in ferritin levels after treatment (90.93 ± 6.883 ng/mL). It can be concluded that serum ferritin increases in HCV patients treated with combined pegylated interferon-alfa (PEG-IFN)-ribavirin than the other treatment regimens. In addition, Serum iron decreases in HCV patients treated with combined PEG-IFNribavirin, while serum iron increases in sofosbuvir dual and trible therapy.

show abstract

“…Suppression of nonadaptive immunity, as well as changes in cytokines, have been found to be associated with disease progression and survival in people diagnosed with hepatocellular carcinoma, which is the most prevalent of the hepatobiliary carcinomas (40–55). The aims of the study were to prospectively: (1) determine the prevalence and distribution of pain, fatigue, and symptoms of depression and their covariation as a cluster in people with hepatobiliary carcinoma; (2) characterize how variation in each individual symptom and/or their covariation as a cluster are associated with changes in immunity; and (3) determine if the symptom clusters, and associated biomarkers, are related to survival in people diagnosed with hepatobiliary carcinoma.…”

Section: Introductionmentioning

confidence: 99%

Cancer-Related Symptom Clusters, Eosinophils, and Survival in Hepatobiliary Cancer: An Exploratory Study

Steel

Kim

Dew

et al. 2010

Journal of Pain and Symptom Management

View full text Add to dashboard Cite

Context The study of symptom clusters is gaining increased attention in the field of oncology in an attempt to improve the quality of life of patients diagnosed with cancer. Objectives The aims of the present study were to: (1) determine the prevalence and distribution of pain, fatigue, and symptoms of depression and their covariation as a cluster in people with hepatobiliary carcinoma; (2) characterize how variation in each individual symptom and/or their covariation as a cluster are associated with changes in immunity; and (3) determine if the symptom clusters, and associated biomarkers, are related to survival in people diagnosed with hepatobiliary carcinoma. Methods Two hundred and six participants diagnosed with hepatobiliary carcinoma completed a battery of standardized questionnaire measuring cancer-related symptoms. Peripheral blood leukocytes were measured at diagnosis, three- and six-month follow-ups. Survival was measured from the date of diagnosis to death. Results Cancer-related symptoms were prevalent and two-step hierarchical cluster analyses yielded three clusters. High levels of pain, fatigue, and depression were found to be associated with elevated eosinophil percentages (F[1,78]=3.1, P=0.05) at three-month and six-month follow-ups using repeated measures ANOVA. Using multivariate latent growth curve modeling, pain was the primary symptom associated with elevated eosinophil percentages between diagnosis and six months (z=2.24, P=0.05). Using Cox regression, vascular invasion and age were negatively associated with survival (Chi-square=21.6, P=0.03). While stratifying for vascular invasion, Kaplan Meier survival analysis was performed and eosinophil levels above the median for the sample were found to be related to increased survival in patients with and without vascular invasion (Breslow Chi-square=4.9, P=0.03). Symptom clusters did not mediate the relationship between eosinophils and survival. Conclusion Cancer-related symptoms, particularly pain and depression, were associated with increased percentages of eosinophils. The presence of symptoms may reflect tumor cell death and be indicative of response to treatment, or other processes, in patients with hepatobiliary carcinoma.

show abstract

A novel human tumor necrosis factor alfa mutein, F4614, inhibits in vitro and in vivo growth of murine and human hepatoma: Implication for immunotherapy of human hepatocellular carcinoma

Cited by 10 publications

References 54 publications

Tumor Necrosis Factor: How to Make a Killer Molecule Tumor-Specific?

Tumor Necrosis Factor: How to Make a Killer Molecule Tumor-Specific?

Evaluation of serum iron and ferritin in different treatment regimens for chronic hepatitis C virus

Cancer-Related Symptom Clusters, Eosinophils, and Survival in Hepatobiliary Cancer: An Exploratory Study

Contact Info

Product

Resources

About