High Immunosuppressive Acidic Protein Research Articles

Prognostic role of immunosuppressive acidic protein in patients with esophageal cancer

Immunosuppressive acidic protein (IAP) suppresses several immune responses in vivo and in vitro , and high preoperative IAP levels could predict the impairment of the host's immunity. In this study prognostic significance of preoperative IAP levels was investigated in 68 esophageal cancer patients with curative resection and eight with non-curative resection. The curative group had significantly lower levels than the non-curative group (432 +/- 183 mg/mL vs. 739 +/- 235 mg/mL, P < 0.0001). The IAP levels were associated with T-status (P < 0.0001), lymphatic invasion (P < 0.05), and p-stages (P < 0.0001). When 5-year survival rate of patients with curative resection was compared by setting various cutoff values of IAP between high and low IAP groups, several cutoff points (400-580 mg/mL) were revealed to be significantly associated with survival. Setting cutoff value of IAP to 560 mg/mL resulted in a most significant difference of 5-year survival rate of patients between the high and low IAP groups (13.9% and 61.5%, P < 0.0001). These data indicate that pre-operative IAP level is a useful parameter to predict the prognosis of esophageal cancer patients after curative resection.

Immunosuppressive acidic protein detects high nuclear grade localized renal cell carcinoma

Objectives To identify a potentially useful preoperative predictor of high nuclear grade renal cell carcinoma (RCC). Methods Our investigation consisted of 181 patients with histologically confirmed clear cell RCC. The positive predictive value, sensitivity, and specificity for detecting nuclear grade RCC were calculated individually for the largest tumor diameter. Hemoglobin, alkaline phosphatase, C-reactive protein, ferritin, and immunosuppressive acidic protein (IAP) levels were also determined in all patients preoperatively. Results The distribution of patients by nuclear grade was 74 patients (41%) with grade 1, 75 (41%) with grade 2, and 32 (18%) with grades 3 and 4. With respect to sensitivity, tumor diameter detected 28 (87.5%) of 32 high nuclear grade RCC specimens, and hemoglobin, C-reactive protein, alkaline phosphatase, ferritin, and IAP detected 10 (31.2%), 25 (78.1%), 8 (25.0%), 16 (50%), and 27 (84.3%) of 32, respectively. Multiple logistic regression analysis showed that a higher than normal C-reactive protein and IAP was associated with a 252% and 405% increase in the odds of a high nuclear grade, respectively. In the Stage T1 cases, elevated IAP was also associated with a 989% increase in the odds of a high nuclear grade. Conclusions IAP level may be a useful predictor for detecting high nuclear grade localized RCC preoperatively.

Prognostic value of preoperative serum immunosuppressive acidic protein in patients with esophageal squamous cell carcinoma.

Immunosuppressive acidic protein (IAP) is a potent biological marker of immunological surveillance in patients with malignant tumors. The aim of this study was to analyze the clinicopathologic significance of IAP in patients with esophageal carcinoma. Preoperative serum IAP concentration was measured by enzyme-linked immunosorbent assay in 115 patients with primary esophageal squamous cell carcinomas. The associations between clinicopathologic factors, C-reactive protein (CRP) values and IAP concentration were determined. Prognostic values were determined by multivariate analysis using Cox's proportional hazards model. The IAP concentration is significantly higher in patients with stage II-IV cancers than in those with stage I cancer. Significant differences in IAP concentration were observed depending upon tumor size, tumor depth, lymph node status and CRP values. A high IAP concentration, more than 500 micro g/mL, was an independent prognostic factor. Thus, a high IAP concentration is associated with tumor progression and poor survival in patients with esophageal squamous cell carcinoma.

Serum Immunosuppressive Acidic Protein as an Interleukin-6 Related Index of Deteriorating Condition in Gastric Cancer Patients

Background/Aims: Immunosuppressive acidic protein (IAP) is an acute-phase reactant which has a close correlation with the impairment of the host’s immunity. The present study aims to investigate the significance of serum IAP as an index of cytokine-related disease status in gastric cancer patients. Methods: Serum IAP levels were determined in 76 gastric cancer patients and 20 healthy subjects. In a subgroup of 39 patients, tissue interleukin-6 (IL-6) concentrations and expression of IL-6 protein in tumor tissues were also examined. Results: The mean serum IAP level in the patients was significantly higher than that in the normal controls. The serum IAP level in the patients was associated with clinicopathological features, such as tumor size and serosal invasion. The prognosis of patients with high IAP levels was significantly worse than that of those with low IAP levels. Moreover, the serum IAP level was closely correlated with various parameters reflecting the host’s nutritional and immunological conditions. Immunohistochemically, IL-6 was overexpressed in the cytoplasm of tumor cells. The IL-6 concentration and immunoreactivity of IL-6 protein in tumor tissue was significantly correlated with the serum IAP level. Conclusions: Elevated serum IAP, which may be upregulated by an activated IL-6 network in tumor tissue, may reflect not only tumor progression, but also a deteriorated condition that is associated with malnutrition and immunosuppression in gastric cancer patients.

Predictive value of serum immunosuppressive acidic protein for lung metastasis after amputation of murine osteosarcoma of the lower limb

A spontaneously occurring murine osteosarcoma cell line (POS-1) was inoculated into the footpads of 88 mice. In 59 mice, the tumor-bearing leg was amputated at 1, 3, 5, or 7 weeks after inoculation and the mice sacrificed at 9 weeks. Lung metastasis was observed in 82.6–100% of the mice undergoing leg amputation at 5 or 7 weeks after inoculation. There were no lung metastasis in the mice amputated at 1 or 3 weeks. The serum immunosuppressive acidic protein (IAP) concentration showed a significant increase at 5 or 7 weeks after inoculation ( P<0.005 and P<0.0005, respectively). When amputation was done 5 weeks after inoculation, the serum IAP concentration increased further to 5.9 times the pre-amputation level 1 week after the amputation. The IAP concentration increased only 1.3-fold in the control group without inoculation. Thus, a high serum IAP concentration before amputation and a further increase after amputation were indicators of lung metastasis in this mouse model of osteosarcoma.

Impact of splenectomy and immunochemotherapy on survival following gastrectomy for carcinoma: Covariate interaction with immunosuppressive acidic protein, a serum marker for the host immune system

The role of the spleen in tumor immunology is still controversial in that it can either enhance or suppress the antitumor immune response depending on the tumor-bearing host. To clarify this biphasic effect of the spleen, a clinical evaluation of splenectomy in conjunction with immunotherapy and the host immune status was performed in gastric cancer patients. The effect of splenectomy and immunotherapy in 253 gastric cancer patients enrolled in a prospective randomized trial (SIP) was analyzed using the Cox's proportional hazards model in terms of the covariate interaction of the preoperative immunosuppressive acidic protein (IAP) level. In patients with high IAP levels (>580 microg/ml) with predicted negative antitumor immune reactions, splenectomy improved the prognosis. In patients with lower IAP values, conversely, the preservation of the spleen and immunotherapy demonstrated a significant benefit to survival. The spleen was shown to have a biphasic activity in terms of its antitumor immune response depending on the IAP level of the patient. The effect of immunotherapy is significantly influenced by the activity of spleen cells. The preoperative IAP level is therefore considered to be a possible indicator for the effectiveness of splenectomy and immunotherapy in curatively resected gastric cancer patients.

Continuous infusion of 5‐fluorouracil and low dose cisplatin infusion for the treatment of advanced and recurrent gastric adenocarcinoma

Several chemotherapy studies have suggested that continuous infusion of 5-fluorouracil (5-FU) is more effective than bolus 5-FU. In addition, 5-FU and cis-Diamminedichloroplatinum-II (cisplatin) in combination have been shown to have synergistic cytotoxicity against several human neoplasms. In this study, the authors evaluated the efficacy and toxicity of continuous infusion of 5-FU and low dose cisplatin infusion (FP therapy) in the treatment of advanced and recurrent gastric adenocarcinoma. The relationship between the response to FP therapy and several factors was also examined. A total of 26 patients fulfilling standard eligibility criteria were enrolled in the trial. FP therapy consisted of 5-FU (350 mg/m2/day every day by continuous infusion) and cisplatin (7.5 mg/m2/day in 100 mL of normal saline infused over 1 hour on Days 1-5 every week) for 4 weeks. A complete response was observed in 2 cases and a partial response in 11 cases, for an overall response rate of 50%. Patients with good performance status (PS) (0-1) and differentiated histologic type showed higher response rates (50.0% and 63.6%, respectively) than patients with poor PS (2 or 3) and undifferentiated histologic type (28.6% and 35.3%, respectively), although there were no significant differences. Patients with low serum levels of immunosuppressive acidic protein (IAP) showed a significantly higher response rate (71.4%) than those with high IAP levels (0%). Toxic effects included leukopenia, thrombocytopenia, nausea, and vomiting; these were not life-threatening and did not require treatment interruption. FP therapy is a promising regimen for patients with advanced and recurrent gastric adenocarcinoma. Serum levels of IAP may predict chemosensitivity.

Continuous infusion of 5‐fluorouracil and low dose cisplatin infusion for the treatment of advanced and recurrent gastric adenocarcinoma

BACKGROUND Several chemotherapy studies have suggested that continuous infusion of 5-fluorouracil (5-FU) is more effective than bolus 5-FU. In addition, 5-FU and cis-Diamminedichloroplatinum-II (cisplatin) in combination have been shown to have synergistic cytotoxicity against several human neoplasms. In this study, the authors evaluated the efficacy and toxicity of continuous infusion of 5-FU and low dose cisplatin infusion (FP therapy) in the treatment of advanced and recurrent gastric adenocarcinoma. The relationship between the response to FP therapy and several factors was also examined. METHODS A total of 26 patients fulfilling standard eligibility criteria were enrolled in the trial. FP therapy consisted of 5-FU (350 mg/m2/day every day by continuous infusion) and cisplatin (7.5 mg/m2/day in 100 mL of normal saline infused over 1 hour on Days 1-5 every week) for 4 weeks. RESULTS A complete response was observed in 2 cases and a partial response in 11 cases, for an overall response rate of 50%. Patients with good performance status (PS) (0-1) and differentiated histologic type showed higher response rates (50.0% and 63.6%, respectively) than patients with poor PS (2 or 3) and undifferentiated histologic type (28.6% and 35.3%, respectively), although there were no significant differences. Patients with low serum levels of immunosuppressive acidic protein (IAP) showed a significantly higher response rate (71.4%) than those with high IAP levels (0%). Toxic effects included leukopenia, thrombocytopenia, nausea, and vomiting; these were not life-threatening and did not require treatment interruption. CONCLUSIONS FP therapy is a promising regimen for patients with advanced and recurrent gastric adenocarcinoma. Serum levels of IAP may predict chemosensitivity. Cancer 1997; 80:1-7. © 1997 American Cancer Society.

Prognostic value of preoperative immunosuppressive acidic protein in patients with gastric carcinoma: Findings from three independent clinical trials

Immunosuppressive acidic protein (IAP) has been reported to have close correlation with the impairment of host immune response. To evaluate the significance of IAP in clinical studies, the prognostic value of preoperative IAP was investigated in clinical trials of patients with gastric carcinoma after curative resection. An appropriate IAP threshold value of 580 micrograms/mL was determined using Cox's proportional hazards model. Five-year survival rates were estimated for high and low IAP groups in three different clinical studies. Meta-analysis was performed based on individual patient data, and summarized hazard ratios were estimated using a stratified proportional hazards model. Meta-analysis of the three clinical trials demonstrated that patients with preoperative IAP levels above the threshold had significantly poorer cancer related survival (P = 0.0039) and absolute survival (P = 0.0023), even after adjustment for the major prognostic factors. Gastric carcinoma patients with an IAP value above the threshold level of 580 micrograms/mL have a higher risk of cancer death and absolute death than patients with an IAP value below the threshold value.

Immunosuppressive Acidic Protein (IAP) and Squamous Cell Carcinoma Antigen (SCC) in Patients with Cervical Cancer

Immunosuppressive acidic protein (IAP) and squamous cell carcinoma (SCC) serum levels were assayed in a group of 63 primary cervical cancer patients. IAP serum levels were significantly higher in cancer patients (median, 630 μg/ml; range, 290-1150) than in controls (median, 290 μg/ml; range, 135-775) (P < 0.01). The percentage of IAP-positive (>613 μg/ml) cases was 50.7%. SCC serum levels were found to be above 2.5 ng/ml in 73% of cervical cancer patients, and in 6% of controls. A statistically significant correlation was observed between IAP and SCC levels in cancer patients (r = 0.35, P < 0.004). When IAP and SCC were considered together the overall sensitivity was 87.3% and an improvement of both predictive value of negative test and accuracy without any significant reduction of predictive value of positive test was found. IAP status correlated with metastatic lymph node involvement. A statistically significant association between a shorter survival and high serum IAP levels was observed. The 24-month overall survival (OS) was 92% for IAP-cases with respect to 65% for IAP+ cases (P = 0.036). In the univariate analysis, advanced stage of disease, clinical parametrial involvement, and lymph node involvement were also associated with poor survival. In the multivariate analysis IAP status showed a statistically significant association with poor survival (P = 0.049), together with lymph node involvement (P = 0.007) and advanced stage of disease (P = 0.008).

A CLINICAL STUDY OF PREOPERATIVE SERUM IMMUNOSUPPRESSIVE ACIDIC PROTEIN IN GASTRIC CANCER

This study was designed to apply immunosuppressive acidic protein (IAP), which increases in serum of cancer-bearing patients, to the treatment of patients with gastric cancer. Preoperative IAP level was measured in 143 resected cases of gastric cancer and the relationship with histopathological findings or prognosis was studied. The high IAP levels were observed in the advanced cases. Significantly increased IAP level was noted in the patients in stage N, with lymphnode metastasis, vascural invasion, and subserosal invasion. In curative resection cases, the 5-year survival rate in the high LAP group (more than 580 μg/dl) was significantly poorer than that of low IAP group. Non-curative resection cases had remarkably poor prognosis compared with curative cases, and there was no significant difference in the 5-year survival rate between high and low IAP groups. Further analysis of curative resection cases by considering background factors revealed that in even early cases such as Stage I+II, ps (-), n (-), v (-), and ly (-), high IAP group had poor prognosis compared with low IAP group, with a significant difference. These findings suggest that preoperative lAP level can offer important information for determining the operative method in the cases of early gastric cancer.

Impaired NK Response of Cancer Patients to IFN‐α but Not to IL‐2: Correlation with Serum Immunosuppressive Acidic Protein (IAP) and Role of Suppressor Macrophage

In vitro NK responses of cancer patients (N = 21) to rIFN-alpha A and rIL-2 were examined. The serum concentration of IAP (immunosuppressive acidic protein) was determined in parallel. Five out of seven patients whose serum IAP contents were within the normal range (270 micrograms/ml to 470 micrograms/ml), had their NK activities significantly augmented by rIFN-alpha A and rIL-2. On the other hand, NK cells from ten out of fifteen patients whose serum IAP concentrations were 650 micrograms/ml or more, were not activated by rIFN-alpha A. NK cells of these fifteen patients yet were capable of responding to rIL-2. NK cells from cancer patients, however, became responsive to rIFN-alpha A by either removal of adherent cells or treatment with indomethacin. Therefore, macrophages in PBMC of cancer patients with high serum IAP levels seem to selectively suppress NK response to rIFN-alpha A by an indomethacin-sensitive mechanisms. It was further shown that PGE2 was not the mediator of this suppression.

Serum Immunosuppressive Acidic Protein (IAP) In Patients with Malignant Head and Neck Tumors

Measurements were carried out on the serum immunosuppressive acidic protein (IAP) level of patients with malignant head and neck tumors. The serum IAP value in patients with malignancies was significantly higher than that in healthy subjects and those with benign tumors. Following treatment, in cases with favorable progress the high IAP values prior to treatment showed a decline, becoming normal. Whereas in cases showing poor progress, there was a delay in reverting to normal values and some were observed to retain the same high values.