Immunosuppressive Acidic Protein Levels Research Articles

Prognostic Value of Immunosuppressive Acidic Protein and Oxidative Stress Status in Critically Ill Patients.

IntroductionThe aim of this study was to determine the prognostic value of admission immunosuppressive acidic protein (IAP), interleukin-6 (IL-6), total oxidant status (TOS), and total antioxidant status (TAS) in 161 critically ill patients.Materials and methodsThis prospective observational study was carried out in the Emergency Department ICU for 6 months. Critically ill patients were included in the study consecutively. The main outcomes were the need for early mechanical ventilation (MV) and in-hospital mortality.ResultsThe mean age of 161 patients was 66.5 ± 17.1 years. The median IL-6 levels of patients who required early MV were significantly higher than of the patients who required no MV (p < 0.001), and the median IL-6 levels in the nonsurvivors were significantly higher than in the survivors (p < 0.001). The median IAP levels were not significantly different between the groups (p = 0.464 for early MV and p = 0.340 for the in-hospital mortality group). The AUCs of IL-6 and TOS for predicting in-hospital mortality were 0.819 and 0.608, respectively.ConclusionThe IAP level on admission to ICU is ineffective in predicting the need for early MV and in-hospital mortality; however, IL-6 level on admission is a strong prognostic predictor in critically ill patients. Our findings showed that the burden of oxidative stress was high in general ICU patients.Clinical significanceOur study showed that increased oxidative stress is an important problem in critically ill patients. If measures are taken to reduce oxidative stress by physicians, the prognosis of critically ill patients will be better.How to cite this articleTutuncu EO, Dundar ZD, Kilinc I, Tutuncu A, Kocak S, Girisgin AS. Prognostic Value of Immunosuppressive Acidic Protein and Oxidative Stress Status in Critically Ill Patients. Indian J Crit Care Med 2021;25(4):405–410.

The neutrophil-lymphocyte ratio and immunosuppressive acidic protein may be useful parameters for predicting depression among middle-aged patients with diffuse large B cell lymphoma.

Patients with diffuse large B cell lymphoma (DLBCL) may experience depression. Growing evidence shows that depression interacts with immunity. However, the relationship between depression and immunity among DLBCL patients has not been investigated, despite reports indicating that patients with DLBCL often suffer from depression. To accurately investigate the relationship between depression and immunity, 82 primarily diagnosed middle-aged patients with DLBCL who received standard chemotherapy were enrolled. The patients were divided into depressed and nondepressed groups according to Zung Self-rating Depression Scale (SDS) scores. Prozac was used to treat patients with depression until their symptoms were alleviated. The concentration of immunosuppressive acidic protein (IAP); percentages of cluster of differentiation (CD)3+, CD4+, and CD8+ T lymphocytes and CD56+ natural killer (NK) cells; absolute lymphocyte count (ALC); and neutrophil--lymphocyte ratio (NLR) were calculated at enrollment and after treatment. A higher score on the depression test was positively associated with serum IAP levels and NLR, and negatively associated with ALC. The levels of NLR and serum IAP in the depressed patients were significantly higher compared to those in the nondepressed patients. Our results suggest for the first time that IAP and the NLR are closely correlated with depression and may be parameters for predicting depression.

Immunosuppressive Acidic Protein- Haematological correlates in HIV infected subjects

Background: Immunosuppressive Acidic protein (IAP) is a marker of the extent of immune defects occurring in most cancers. Its correlation with CD4 cell count used as an indicator of immune function and disease progression in Human Immuno-deficiency Virus (HIV) infection is not well documented.Aims and Objectives: To determine if IAP levels correlates with immunosupression and haematopathology occurring in HIV/AIDS infection.Materials and Methods: This cross sectional study was conducted at the Federal Teaching Hospital, Ido-Ekiti. One hundred and five participants consisting of 85 HIV infected test subjects and 20 control subjects were enrolled into the study. CD4 counts was obtained using SL Cyflow machine, IAP levels determined using ELISA kit for human IAP and Full blood count for all participants was obtained using Sysmex KX-21N Haematology Analyzer. Regression and correlation analysis was done on data using SPSS 28.Results: IAP showed a negative correlation with CD4 count (r= -0.6), (r= -0.9) and (r= -0.2) in the ART, NART and control groups. The pattern of the results was similar with other parameters except in Neutrophils (r= 0.2) (r= 0.3) and (0.1), Eosinophil (r= 0.6) (r= -0.4) and (r= -0.2) and Lymphocyte (r = -0.3) (r= -0.02) and (r= 0.05) in the ART, NART and control groups respectively. CConclusion: The outcome of this study show that a strong negative relationship exist between IAP and other immunohaematological parameters used for monitoring Immune status in HIV infection; however the information gotten is not sufficient to indicate IAP as a predictor of immune status in HIV infection. Further studies are therefore required to better elucidate the mechanism of increased IAP levels at different clinical stages of HIV infection.Asian Journal of Medical Sciences Vol.8(5) 2017 8-16

Prognostic markers for immunochemotherapy using tegafur -uracil (UFT) and protein-bound polysaccharide K (PSK).

We previously reported that PSK-induced lymphocyte blastogenesis reaction (PSK-stimulation index; PSK-SI) may be a prognostic marker for immunochemotherapy using PSK in gastrointestinal cancer patients. In this study we evaluated the usefulness of PSK-SI as a prognostic marker for PSK therapy at higher and lower serum immunosuppressive acidic protein (IAP) levels. 98 gastric and 135 colorectal cancer patients were analyzed. PSK-SI and serum IAP levels were measured preoperatively. After operation, patients received UFT and PSK for two years. There were no differences between patients with higher and those with lower PSK-SI with respect to the clinicopathological factors. In patients with higher serum IAP levels (> or = 500 microg/ml), recurrence-free survival (RFS) and overall survival (OS) were apparently more favorable in the higher PSK-SI group (gastric cancer; > or = 1.75, colorectal cancer; > or = 2.1) than in lower PSK-SI group, although the differences were not significant. Serum IAP levels and PSK-SI may be useful markers for prediction of response to immunochemotherapy using PSK, although further studies are necessary.

Depression in older patients with advanced colorectal cancer is closely connected with immunosuppressive acidic protein

Colorectal cancer (CRC) is one of the most common tumors. CRC patients are susceptible to suffering from depression. Whether the immune system of CRC patients with depression is impaired or stimulated is controversial. Possible reasons for this conflict are the involvement of confounding factors, such as the age of the patient, the stage of the CRC and the types of treatment in previous studies. To demonstrate clearly the relationship between depression and the immune system in the context of CRC, the present study included only older patients with advanced CRC who received only chemotherapy, and the study adopted immunosuppressive acidic protein (IAP) as an immune parameter for the first time. A total of 56 older patients with advanced CRC completed the Zung Self-Rating Depression Scale (SDS) and were divided into two groups according to SDS scores. The patients exhibiting depression were treated with fluoxetine until their symptoms remitted. The serum levels of IAP and the percentages of CD3-positive (CD3+), CD4+, CD8+ T lymphocytes and CD56+ natural killer (NK) cells and Neutrophil-lymphocyte ratio (NLR) were calculated at the time of enrollment and once the symptoms remitted. Correlation analyses revealed that the SDS score was positively associated with serum IAP levels but negatively associated with CD3 and CD4 levels. Among the depressed and non-depressed patients, serum IAP levels and the percentages of CD3 and CD4 cells were dramatically different. After the depression symptoms were treated, the IAP levels dramatically decreased, while the levels of CD3, CD4, CD8 and CD56 were unchanged. All of above suggested that IAP was closely correlated with depression and might be a relatively objective parameter for predicting depression.

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.

Serum immunosuppressive acidic protein reflects systemic deterioration of colorectal cancer patient condition

Immunosuppressive acidic protein (IAP) is a potent biological marker for immunological surveillance in patients with malignant tumors. This study aimed to investigate the significance of serum IAP as an index of disease status, clinicopathological findings and prognosis in colorectal cancer. A total of 101 patients with colorectal cancer and 80 normal volunteers were included in this retrospective trial. Preoperative serum IAP was assayed using a commercially available enzyme-linked immunosorbent assay kit. The serum IAP level in the patients, which was not associated with clinicopathological features except for tumor size, was significantly higher than that in controls. The serum IAP level was closely correlated with percent body weight loss, serum albumin and cholinesterase, and percentage of circulating lymphocytes reflecting the host's nutritional and immunological conditions. Interestingly, these parameters were not associated with factors reflecting disease progression except for tumor size. The prognosis of patients with higher IAP levels was significantly worse than that of patients with lower IAP levels. Furthermore, an elevated serum IAP level was an independent prognostic marker in all patients. The preoperative serum IAP level may reflect the general condition of colorectal cancer patients, and thus may predict long-term survival independently of stage progression.

Cell transfer regimens in patients with highly advanced surgically unresectable non-small cell lung cancer: Significantly improved overall survival in patients with lower levels of serum immunosuppressive acidic protein

Sixty-one non-small cell lung cancer (NSCLC) patients with stage II and III/IV were enrolled and 49 completed immunotherapy. Patients were grouped based on immunosuppressive acidic protein (IAP). All patients received monthly intravenous infusions containing 1 x 10(10) (mean cell number per patient) ex vivo expanded and IFN-alpha-treated peripheral blood mononuclear cells. No patients had grade 2 or greater adverse events. The patients with < or = 580microg/ml of serum IAP levels (n=33) had significantly longer recurrence-free survival than those with > 580microg/ml of serum IAP levels (n=16). Patients with lower IAP levels are still under immunotherapeutic control after 27 months free of recurrence. The IAP levels may be a prognostic marker for treatment efficacy in NSCLC. This immunotherapeutic regimen was feasible and well tolerated in patients with advanced NSCLC in terms of prolongation of survival.

Serum Immunosuppressive Acidic Protein Levels in Patients With Severe Acute Pancreatitis

In severe acute pancreatitis (SAP), immunologic impairment in the early phase may be linked to subsequent infectious complications. Immunosuppressive acidic protein (IAP) is an immunosuppressive factor to be present in serum and ascites of cancer patients, and it is used as a tumor marker and an index of immune status of cancer hosts. We measured serum IAP levels in 42 patients with SAP (Japanese severity score [JSS] > or = 2) on admission and analyzed the relationships with disease severity, pancreatic necrosis, blood biochemical parameters on admission, and clinical outcome (infection and death). Serum IAP level increased 791 +/- 285 microg/mL (range, 159-1430 microg/mL) on admission and recognized abnormal high level (normal range, < 500 microg/mL) in 37 patients (88.1%). Serum IAP level was significantly lower in patients of stages 3 and 4 (JSS > or = 9) (678 +/- 187 microg/mL) than that in patients of stage 2 (2 < or = JSS < or = 8) (848 +/- 311 microg/mL). It was also significantly lower in patients whose Ranson score was 5 or higher (674 +/- 287 microg/mL) than that in patients whose Ranson score was 4 or less (910 +/- 287 microg/mL). Moreover, it was significantly lower in patients with pancreatic necrosis (693 +/- 194 microg/mL) than that in patients without pancreatic necrosis (922 +/- 336 microg/mL). Among the blood biochemical parameters on admission, serum IAP was significantly negatively correlated with hematocrit, serum lipase, and serum interferon gamma and was significantly positively correlated with serum total protein. Serum IAP levels in patients of stage 2 reached higher peak at 7 days after admission and decreased more rapidly than those in patients of stages 3 and 4. Serum IAP levels were elevated in patients with SAP but were significantly lower in patients with higher grade of severity or pancreatic necrosis. These results suggest that serum IAP levels may be related to systemic inflammatory response and reflect the immunoresponsiveness in patients with SAP.

Neutrophil Elastase Inhibitor (Sivelestat) Preserves Antitumor Immunity and Reduces the Inflammatory Mediators Associated with Major Surgery

To examine the effects of the administration of perioperative sivelestat, a selective neutrophil elastase inhibitor, on tumor immunity and inflammatory mediators in patients who undergo major surgery. Thirteen patients admitted to the hospital for elective surgery were equally randomized into one of two groups: the Sivelestat group (n = 6) and the control group (n = 7). Thereafter, the immunosuppressive acidic protein (IAP), serum interleukin-6 (IL-6), and type 1/type 2 T-helper cell balance were all assessed at several time points before and after surgical intervention. The serum IL-6 values at 1 and 12 h after surgery and on postoperative days 1 and 3 were all significantly lower in the sivelestat group than in the control group. The IAP values at postoperative days 7 and 28 in the sivelestat group were also significantly lower than those in the control group. There was a significant correlation between the IL-6 level at 1 h after surgery and the IAP level at postoperative days 7 and 28. In this preliminary study, the perioperative administration of sivelestat was thus suggested to reduce surgical stress by decreasing the cytokine release and preserving the antitumor immunity.

10 Inflammatory biomarkers: measurement and clinical outcomes

Objectives. To determine the clinical significance and predictive value of three acute phase reactants (erythrocyte sedimentation rate, C-reactive protein, and ferritin), as well as basic fetoprotein (BFP) and immunosuppressive acidic protein, in patients with renal cell carcinoma.Methods. Erythrocyte sedimentation rate, C-reactive protein, ferritin, BFP, and immunosuppressive acidic protein levels were measured in 92 patients with renal cell carcinoma diagnosed in 1989 to 1999. The levels were compared with the clinical stage and nuclear grade, and their predictive values of survival were evaluated statistically.Results. All markers, with the exception of BFP, correlated with each other and with the clinical stage and nuclear grade. BFP did not correlate with the acute phase reactants. The log-rank test revealed that the levels of C-reactive protein, immunosuppressive acidic protein, and ferritin significantly influenced survival. Multivariate stepwise analysis identified ferritin as the only independent and significant prognostic marker (hazard ratio = 5.624, P = 0.001). However, when age, sex, clinical stage, and nuclear grade were entered into the same analysis, only clinical stage was an independent marker of prognosis.Conclusions. The results of our study demonstrated that serum ferritin is the most useful marker among five tested factors for staging and predicting survival, although the clinical stage is the best parameter that predicts the prognosis of patients with renal cell carcinoma accurately.

Serum immunosuppressive acidic protein doubling time as a prognostic factor for recurrent renal cell carcinoma after nephrectomy

Objectives To identify the prognostic factors in patients with recurrent renal cell carcinoma after nephrectomy, various factors were assessed, with special attention to serum immunosuppressive acidic protein (IAP) and its doubling time. Methods Age, sex, stage, grade, histopathologic type, primary tumor size, site and number of metastatic organs, time to recurrence, IAP levels before nephrectomy and at the diagnosis of recurrence, and IAP doubling time just before recurrence were analyzed in 125 patients with recurrent renal cell carcinoma after nephrectomy. Results Univariate analysis identified stage, grade, histopathologic type, primary tumor size, time to recurrence, IAP level at the diagnosis of recurrence, and IAP doubling time as significant prognostic factors. After exclusion of confounding factors, multivariate analysis showed that IAP doubling time was the most potent independent prognostic factor. Patient survival rates dichotomized according to IAP doubling time were compared at 100-day intervals from 100 to 700 days and 1000 and 2000 days. The maximal difference in survival rate was found when the cutoff level in the IAP doubling time was set at 200 days. Conclusions The results of our study have shown that the IAP doubling time is a potent prognostic factor in patients with recurrent renal cell carcinoma. Periodic checkups with serum IAP level monitoring are recommended to predict prognosis after recurrence.

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.

P0651 A PEDIATRIC PATIENT WITH CROHN???S DISEASE AND 1p36 DELETION SYNDROME

Introduction: Crohn’s disease(CD) is a multifunctional disorder involving polygenic defects. Here we report a pediatric case of CD associated with 1p36 defect. Methods: Case report Results: The patient was born by cesarean section after 29-week gestation due to the severe toxemia of pregnancy. Her birth weight was 814g, and serious asphyxia and hypotonia were observed. MR imaging disclosed periventricler leukomalacia. In late infancy, she showed severe psycomotor retardation, and infantile spasm. She also had small-sized hands and feet and peculiar countenance such as microcephaly, protruded forehead, sunken eyes, low set ears and a sharp jaw. These features suggested that she had a disorder related to multiple gene abnormalities or chromosomal alteration. She could eat any kinds of soft foods with an assistant, but was bedridden because her motor development was quite retarded. At the age of 5, she suffered from intractable diarrhea, bloody excrement and a fever. She was 100cm in height and 9.8kg in weight (2kg loss in a half-year). She had edema of a whole body caused by quite severe malnutrition. She was in bad temper when her abdomen was examined for detection of two masses in the right flank and in the left abdominal region. Blood examination showed that marked accelerated erythrocyte sedimentation rate, high levels of immunosuppressive acidic protein and sialic acid. Retrograde colonography showed two lesion of cobblestone appearance in sigmoid colon and severe stenosis in descending colon. Histological findings showed chronic nonspecific inflammation of colon but noncaseous granuloma was not detected. All other clinical and laboratory findings were compatible with the diagnosis of CD. Intravenous hyperalimentation (IVH) was undertaken and two courses of methylpredonisolone pulse therapy followed by oral predonisolone(PSL), azathioprine and salazosulfapyridine were given. But her symptom was PSL dependent and even some side effects of it were observed. Therefore an administration of infliximab (IFX) (5mg/kg) was performed. Her symptoms and laboratory data responded immediately to the IFX. Elementary diet could be started and PSL dosage could be reduced with withdrawal of IVH. After 7 weeks, she had recurrence of slight bloody stool, and IFX with hydrocortisone was re-administered. The remission was obtained again and continued for over 17 weeks. The FISH analysis with subtelomere probe revealed that she has 1p36 deficiency syndrome. Conclusion: This is the first report of 1p36 deletion syndrome patient with CD. Cho et. al. (1998) reported that 1p37 has a high lod score using linkage analysis of CD families. Analysis of this extremely rare case may indicate a candidate gene in CD.

Significance of postoperative adjuvant immunochemotherapy after curative resection of colorectal cancers: Identification of responders incorporating the age factor

To identify responders when protein-bound polysaccharide (PSK) is used in adjuvant immunochemotherapy after curative resection of colorectal cancers, we examined the host and tumor factors that affect the prognosis incorporating the age factor. A total of 101 patients who had undergone macroscopic curative resection of colorectal cancer were treated with mitomycin C + fluoropyrimidine oral antineoplastics + PSK (MFP therapy) for two years in principle. These cases were divided into two age groups of <65 years [n=55; 54.8 +/- 8.3 years (mean +/- SD)] and > or =65 years (n=46; 69.1 +/- 3.3 years). Host factors including humoral factors (complement C3 and C4), immunosuppressive acidic protein (IAP), lymphocyte transformation (cellular factors) induced by various mitogens [phytohemagglutinin (PHA), pokeweed mitogen (PWM), and PSK], and tumor markers (CEA, CA19-9) were measured. The cases were divided by the cut-off value of each parameter into > or = cut-off value and < cut-off value groups, and the 5-year survival rates were compared. The cut-off values obtained for these parameters and the tumor factor (Dukes class) were subjected to multivariate analysis to identify the markers that affect prognosis. The 5-year mortality rate was 74.5% in the <65 age group and 56.8% in the > or =65 age group, with a tendency of better prognosis in the <65 age group (p=0.1109). Compared to the <65 age group, the > or =65 age group showed higher levels of C3 (2-way ANOVA: p=0.0582), C4 (p=0.0009) and IAP (p=0.0110) over time, but lower PSK-induced stimulation index (SI) as an indicator of cellular immunity) (p=0.0001) and PHA-induced SI (p=0.2650) over time. These results indicated that compared to patients aged <65 years, patients aged > or =65 years were characterized by lowered cellular immunity in addition to augmented complement production and an aggravated immunosuppressive state, suggesting the presence of some differences in host immune function with aging. Using the Cox proportional hazard model, the prognostic determinant was found to be Dukes C in the <65 age group, and CEA level in the > or =65 age group. The present results suggested that analysis of prognostic determinants of this therapy should take into account the age factor. Especially in elderly subjects, responders to PSK may be identified using the preoperative CEA value.

Life‐Prolonging Effect of Immunocell BAK (BRM‐Activated Killer) Therapy for Advanced Solid Cancer Patients: Prognostic Significance of Serum Immunosuppressive Acidic Protein Levels

AbstractFor Abstract see ChemInform Abstract in Full Text.

Life-prolonging effect of immunocell BAK (BRM-activated killer) therapy for advanced solid cancer patients: prognostic significance of serum immunosuppressive acidic protein levels.

We devised an innovative type of immunocell therapy called BRM (biological response modifier)-activated killer (BAK) therapy, which utilizes most of non-MHC (major histocompatibility complex) restricted lymphocytes, CD56+ cells including gammadelta T cells and NK cells. Peripheral blood lymphocytes were selected by immobilizing them with anti-CD3 monoclonal antibody, cultured for 2 weeks with serum-free medium containing IL-2, and then were reactivated by 1,000 U/ml of IFN-alpha for 15 min. The patients were infused with about 6x10(9) BAK cells by intravenous drip infusion at 1-month intervals. All advanced solid cancer patients who had received chemotherapy but for whom it was not effective or have refused chemotherapy were included in the present study. A good marker of impairment of host immune response by chemotherapy is an immunosuppressive acidic protein (IAP) level in serum above 580 microg/ml; survival rates were compared with the high (> 580 microg/ml) and the low (< or = 580 microg/ml) serum IAP groups. We enrolled in this study 23 immunosuppressed patients whose IAP levels in serum were over 580 microg/ml, and 42 immunoreactive solid cancer outpatients whose IAP level in serum were under 580 degreesg/ml and whose performance statuses were over 80% on the Karnofsky scale. After giving informed consent, patients were treated with BAK therapy on an outpatient basis at our hospital. The ethical review board of the Miyagi Cancer Center approved this pilot study. Treated with BAK therapy, the mean survival of immunosuppressed patients was 4.6 months. On the other hand, survival for one of immunoreactive advanced postoperative patients (stage IV) and inoperable lung cancer patients (stage IIIb) was 24.7 months. The difference in survival between the 2 groups was significant (P < 0.01). This shows that BAK therapy is not indicated for an advanced cancer patient whose serum IAP is over 580 microg/ml, perhaps due to extensive chemotherapy. Overall response to BAK therapy was complete response (CR) in 5 cases, partial response (PR) in 1 case, and prolonged no change (NC) in 26 cases, with an effectiveness rate at 76.2% in 42 advanced stage IIIb and IV cancer patients. BAK therapy has a life-prolonging effect without any adverse effects and maintains satisfactory quality of life (QOL) for advanced cancer patients.

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.

Significance of postoperative adjuvant immunochemotherapy after curative resection of colorectal cancers: Association between host or tumor factors and survival

We examined the relationship between host as well as tumor factors and postoperative survival rate in patients who received combination therapy of mitomycin C + fluoropyrimidine oral antineoplastics + protein-bound polysaccharide K (PSK) (MFP therapy) after curative resection of colorectal cancer. Markers that determine prognosis, such as preoperative humoral factors (complement 3 and 4), immunosuppressive acidic protein (IAP), lymphocyte transformation (cellular factors) induced by phytohemagglutinin (PHA), pokeweed mitogen (PWM), and PSK, and various tumor markers (CEA, CA19-9) were measured. For each parameter, patients were divided into a high-level and a low-level group according to a predetermined cut-off value, and survival rates were compared between the two groups. The host factors that determined prognosis were 1-month postoperative IAP level [IAP(1M)], preoperative PHA value, and preoperative CA19-9 level. The levels of IAP(1M) <740 microg/ml, preoperative PHA > or =210 (SI value), and preoperative CA19-9 <13 U/ml were associated with a favorable prognosis. When combined with the tumor factors, the prognosis was favorable in Dukes A+B cases with preoperative CA19-9 <13 U/ml, and in Dukes C cases with preoperative PHA > or =210 SI. By the Cox proportional hazard model analysis, among IAP, PHA and CA19-9, CA19-9 was the strongest host factor associated with the prognosis of MFP therapy.

Prognostic value of serum immunosuppressive acidic protein in renal cell carcinoma

To determine whether the immunosuppressive acidic protein (IAP) could be a useful marker for renal cell carcinoma (RCC), serum IAP levels were compared with clinicopathological features in RCC patients. Furthermore, IAP cutoff level to predict the recurrence was determined using receiver operating characteristics (ROC) curve analysis. Between January 1994 and December 1998, pretreatment serum IAP was measured in 123 consecutive patients with PCC at Kitasato University Hospital. Ninety-eight patients were received radical surgery and 86 patients were performed as clinically curable renal cell carcinoma (pT1-pT3N0M0). ROC curve analysis was utilized to set the cutoff value of IAP for prediction of cancer recurrence. Significance of prognostic factors in RCC recurrence was analyzed by Cox proportional hazard model. The mean age of the 123 patients was 58.6 years (range 33 to 90, median 59). The mean follow-up period was 24.8 months (range 1 to 78, median 26). The median IAP levels were 447 ug/ml in stage I, 629 ug/ml in stage II, 588 ug/ml in stage III and 1,150 ug/ml in stage IV (p < 0.05). Tumor size and venous involvement were significantly associated with IAP concentrations (p < 0.05). However, tumor grade did not correlate with IAP level. Of 86 patients with clinically curable tumor, 79 patients were disease-free after median follow-up of 27 months. Using ROC curve analysis, IAP cutoff level for prediction of cancer recurrence was set at 620 ug/ml. Disease-free survival rate in patients with preoperative IAP levels of 620 ug/ml or lower was 98.5% (67/68) at 27 months postoperatively, whereas that in patients with IAP greater than 620 ug/ml was 75.0% (12/18). This difference was statistically significant (p < 0.05). Results of multivariate analysis revealed that preoperative IAP and pT stage were statistically significant factors for tumor recurrence after radical surgery (p < 0.05). The present study indicates that preoperative IAP level is a useful prognostic marker in patients with RCC. In particular, patients with clinically curable tumors (pT1-3N0M0), whose preoperative IAP levels greater then 620 ug/ml may have high risk for recurrence after radical nephrectomy.