Local injection of OK-432/Fibrinogen gel into head and neck carcinomas

Kumazawa, Hirobumi; Yamashita, Toshio; Tachikawa, Takuya; Minamino, Masayuki; Nakata, Yukari

doi:10.1016/0959-8049(94)00238-z

Cited by 8 publications

(9 citation statements)

References 9 publications

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“…Still, TAMs may in some cytokine environments have tumour suppressive potentials, which probably explains observations of improved prognosis associated with high numbers of TAMs in some other types of malignancies [ 33 , 34 ]. The observed reductions in HNSCC tumour mass when injected with biological response modifiers such as OK-432, may be in part be explained by such macrophage activation [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

Stimulated monocyte IL-6 secretion predicts survival of patients with head and neck squamous cell carcinoma

et al. 2008

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BackgroundThis study was performed in order to determine whether monocyte in vitro function is associated with presence, stage and prognosis of head and neck squamous cell carcinoma (HNSCC) disease.MethodsProspective study describing outcome, after at least five years observation, of patients treated for HNSCC disease in relation to their monocyte function. Sixty-five patients with newly diagnosed HNSCC and eighteen control patients were studied. Monocyte responsiveness was assessed by measuring levels of monocyte in vitro interleukin (IL)-6 and monocyte chemotactic peptide (MCP)-1 secretion after 24 hours of endotoxin stimulation in cultures supplied either with 20% autologous serum (AS) or serum free medium (SFM). Survival, and if relevant, cause of death, was determined at least 5 years following primary diagnosis.ResultsAll patients, as a group, had higher in vitro monocyte responsiveness in terms of IL-6 (AS) (t = 2.03; p < 0.05) and MCP-1 (SFM) (t = 2.49; p < 0.05) compared to controls. Increased in vitro monocyte IL-6 endotoxin responsiveness under the SFM condition was associated with decreased survival rate (Hazard ratio (HR) = 2.27; Confidence interval (CI) = 1.05–4.88; p < 0.05). The predictive value of monocyte responsiveness, as measured by IL-6, was also retained when adjusted for age, gender and disease stage of patients (HR = 2.67; CI = 1.03–6.92; p < 0.05). With respect to MCP-1, low endotoxin-stimulated responsiveness (AS), analysed by Kaplan-Meier method, predicted decreased survival (χ = 4.0; p < 0.05).ConclusionIn HNSCC patients, changed monocyte in vitro response to endotoxin, as measured by increased IL-6 (SFM) and decreased MCP-1 (AS) responsiveness, are negative prognostic factors.

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Section: Discussionmentioning

confidence: 99%

Stimulated monocyte IL-6 secretion predicts survival of patients with head and neck squamous cell carcinoma

et al. 2008

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“…This was based on a meta‐analysis including 8009 patients from eight randomized clinical phase III trials. There are also reports suggesting that patients with other cancers, like head and neck squamous cell carcinoma [12], may benefit from OK‐432 treatment. OK‐432 may also be used as a maturation factor for DCs cells as part of vaccination therapy of patients with cancer [13].…”

Section: Introductionmentioning

confidence: 99%

MAPKs ERK and p38, but not JNK Phosphorylation, Modulate IL‐6 and TNF‐α Secretion Following OK‐432 In Vitro Stimulation of Purified Human Monocytes

Olsnes¹,

Olofsson²,

Aarstad³

2011

Scand J Immunol

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Interaction between the immune system and cancer allows for the use of biological response modifiers, e.g. OK‐432, in cancer therapy. OK‐432, penicillin‐killed Streptococcus pyogenes, is used in treating carcinomas, but also lymphangiomas. We have studied the role of monocytes (MOs) in the immune response to OK‐432 by examining IL‐6 and tumour necrosis factor (TNF)‐α secretion after in vitro MO stimulation with OK‐432, to some extent in comparison with lipoteichoic acid (LTA) and lipopolysaccharide (LPS). LTA stimulation of whole blood gave IL‐6 but not TNF‐α secretion, as previously shown with OK‐432 stimulation, whereas both cytokines were secreted following LPS stimulation. Addition of the MAPK kinase (MAPKK) MEK inhibitor U0126 inhibited IL‐6/TNF‐α secretion in a dose‐dependent manner. Flow cytometry and to some extent Western blot (Wb) analyses showed that MAPK ERK, located downstream of MEK1/2, is predominantly phosphorylated at isolation from peripheral blood. Addition of the p38 MAP kinase inhibitor SB202190 decreased MO IL‐6/TNF‐α production upon OK‐432 stimulation in a dose‐dependent manner. Addition of the MAPK JNK inhibitor SP600125 did not systematically change the MO IL‐6/TNF‐α OK‐432 response. Flow cytometry showed that when stimulating the MOs before isolation from blood, LPS yielded ERK phosphorylation and LPS/LTA p38 phosphorylation, whereas OK‐432 had no effects on phosphorylation levels. In conclusion, we have shown that OK‐432 resembles TLR2 more than TLR4 stimulation of MOs and depends on MAPKK MEK and MAPK p38, but not on JNK phosphorylation. The MEK and p38 MO OK‐432 stimulation dependence is possibly related to the differentiation of cells of the MO lineage.

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“…Furthermore, Oba et al [22] have shown that patients with resectable gastric carcinoma treated with adjuvant immunochemotherapy, with OK-432 as one component, may improve their survival (performed was a meta-analysis on 8,009 patients from eight randomized clinical phase III trials). There are also reports suggesting that patients with other cancers, such as HNSCC [23], may benefit from OK-432 treatment. OK-432 may also be used as a maturation factor for dendritic cells (DCs) as part of vaccination therapy of cancer patients [24].…”

Section: Introductionmentioning

confidence: 99%

Mononuclear phagocytes in head and neck squamous cell carcinoma

Kross

Heimdal

Aarstad

2009

Eur Arch Otorhinolaryngol

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The head and neck squamous cell carcinoma microenvironments contain many immune cells and their secretory products. Many of these cells belong to the mononuclear phagocyte system. The aim of this review is to study the interactions between mononuclear phagocytes and head and neck squamous cell carcinoma tissue. The role of inflammation in tumours and the cytokine interleukin-6 will be highlighted. Future therapy strategies in the treatment of head and neck cancer might be directed towards mononuclear phagocytes and their cytokine production.

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Local injection of OK-432/Fibrinogen gel into head and neck carcinomas

Cited by 8 publications

References 9 publications

Stimulated monocyte IL-6 secretion predicts survival of patients with head and neck squamous cell carcinoma

Stimulated monocyte IL-6 secretion predicts survival of patients with head and neck squamous cell carcinoma

MAPKs ERK and p38, but not JNK Phosphorylation, Modulate IL‐6 and TNF‐α Secretion Following OK‐432 In Vitro Stimulation of Purified Human Monocytes

Mononuclear phagocytes in head and neck squamous cell carcinoma

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