Evaluation of an automated extraction system in combination with Affigene CMV Trender for CMV DNA quantitative determination: comparison with nested PCR and pp65 antigen test.

CMV viral load quantitation is a powerful tool to assist clinicians in making accurate diagnoses, managing post-transplant CMV disease and monitoring antiviral therapy. The aim of this study was to evaluate the performance of Affigene CMV Trender for CMV viral load determination used in combination with a non-dedicated nucleic acid extraction system (BioRobot MDx) for high-throughput routine. Linearity, reproducibility and sensitivity were examined. Clinical samples were used to compare results obtained with the Affigene CMV Trender, with an "in house" nested PCR used for routine diagnosis and with pp65 antigenemia. The results indicated that the test is linear in the range of 1.81-5.18 Logcopies/ml and that sensitivity is 77 copies/ml. The concordance of the Affigene CMV Trender with nested PCR was high, (k=0.91, IC 95%=0.82-1.00), whereas a substantial concordance with pp65 antigenemia was observed (k=0.64, IC 95%=0.54-0.73). In conclusion, combined use of a non-dedicated automated nucleic acid extraction method with the Affigene CMV Trender results in an accurate high throughput system, suitable for routine laboratory monitoring of CMV infection.

Activation of interferon response genes and of plasmacytoid dendritic cells in HIV-1 positive subjects with GB virus C co-infection.

GB virus C (GBV-C) coinfection has a protective role in Human Immunodeficiency Virus (HIV) infection, and increases the duration of suppression of HIV-1 viremia in patients under Highly Active Anti-Retroviral Therapy (HAART). Since innate antiviral response may be involved in the protection, we analyzed the possible role of GBV-C as activator of innate immunity. To this aim, we measured the extent of activation of the interferon (IFN) system and of circulating Dendritic Cells (DC) in vivo, and the ability of GBV-C to activate these functions in vitro. Activation of IFN system and of circulating DC was compared in GBV-positive and -negative HIV-1 co-infected patients with HAART-driven suppression of HIV-1 viremia. Endogenous levels of IFN-gamma and RNA-dependent protein kinase (PKR) mRNA were significantly higher in peripheral blood mononuclear cells (PBMC) from GBV-C-positive when compared to GBV-C-negative patients. IFN-gamma expression was correlated with all the Interferon response genes (IRGs) and with GBV-C viremia. The frequency of circulating plasmacytoid DC (pDC) expressing the CD80 activation marker was increased in GBV-C-positive patients, and was correlated with GBV-C viral load. In vitro experiments indicated that GBV-C is able to induce IFN-gamma expression in PBMC. In addition, in PBMC cultures GBV-C induced an increase of CD80 expression by pDC, that was reduced by antibody to IFN-gamma. Our data indicate that in HIV-positive patients GBV-C coinfection promotes the activation of IFN-gamma and downstream IRG expression, as well as with the activation/maturation of circulating pDC. GBV-C-driven IFN-gamma activation is, at least in part, responsible for the increased maturation of pDC. This crosstalk may suggest a role for GBV-C coinfection in boosting the innate antiviral response to HIV infection.

Ability of peripheral blood mononuclear cells to activate interferon response in vitro is predictive of virological response in HCV patients.

The most reliable predictor of treatment efficacy in hepatitis C is HCV viremia decay at week 12 [early virological response (EVR)]. We investigated whether the ability of peripheral blood mononuclear cells (PBMC) to mount an interferon (IFN) response in vitro could be predictive of EVR. Fifteen patients treated with PEG IFNalpha + RBV, with pre-therapy frozen PBMC, were retrospectively selected. After a 3 hr PBMC exposure to IFNalpha in vitro, up-regulation of mRNA for IFN-stimulated genes (ISG) was measured by membrane super-array. ISG mRNA levels in unstimulated PBMC were low, but beta2M and CASP1 were significantly higher in EVR vs non-EVR. ISG mRNA up-regulation by IFN was more pronounced in EVR vs non-EVR. For 7 genes (IP-10, IFIT1, IFIT2, IFIT3, TRAIL, KIAA1628 and OAS2) cut-off levels were established, by ROC analysis, able to correctly classify all EVR and non-EVR. Early virological response to PEG IFNalpha +RBV is correlated with the pre-therapy ability of PBMC to activate an IFN response in vitro. If validated in a wider cohort of patients, the ability of this set of ISG to discriminate between EVR and non-EVR may be useful for pre-therapy evaluation, particularly in patients with unfavourable combinations of conventional response predictors.

Localized morphea after breast implant for breast cancer: A case report.

PURPOSE: Early breast cancer follow-up guidelines for patients who underwent surgery suggest a regular and accurate clinical examination of the breast area, for an early identification of cutaneous or subcutaneous breast cancer relapse. Nonetheless, breast skin lesions arising in patients treated with mastectomy for breast cancer can be caused by several diseases. A series of diagnostic hypotheses should be considered, not only focusing on cutaneous metastasis, but also on dermatologic and systemic diseases. CASE REPORT: In February 2015, a 37-year-old patient underwent a right subcutaneous mastectomy for stage IIA breast cancer. Five months after beginning adjuvant chemotherapy, she noted hyperpigmentation and thickening of the skin on the right breast. Differential diagnosis included local relapse, skin infection, lymphoma, or primary cutaneous disease, and a skin biopsy was performed. The histopathologic specimen showed full-thickness sclerosis, with features of localized morphea. Therapy with clobetasol was prescribed, with progressive resolution of the thickness. The collaboration between many professionals in a multidisciplinary team (oncologist, dermatologist, plastic surgeon, and pathologist) was crucial to achieving the diagnosis. CONCLUSION: In the literature, some articles describe correlation between connective tissue diseases and silicone breast implants, but the pathogenetic mechanisms are unknown. We report a rare case of breast morphea after positioning a silicone implant in a patient who had undergone mastectomy. This clinical report represents an interesting model of multidisciplinary management of a patient with breast cancer who developed an uncommon dermatologic disease. Further studies are needed to clarify the association between silicone implants and breast morphea.

MMP-2, MMP-9, VEGF and CA 15.3 in breast cancer.

BACKGROUND: Matrix metalloproteinases (MMPs) are a family of extracellular matrix degrading proteinases. Owing to their matrix-degrading abilities and high expression in advanced tumours, MMPs were originally implicated in cancer progression, invasion and metastasis. PATIENTS AND METHODS: In this study, the correlation was determined between the expression of gelatinases (MMP-2 and MMP-9) in the sera of breast cancer patients from zymographic analysis and serum concentrations of VEGF and CA 15.3, before surgery and after 1 and 6 months; the association of both markers with clinicopathological features including histological type, stage of disease and estrogen (ER) and progesterone (PgR) receptors status were also analysed. In all, 88 breast cancer patients and 20 healthy women were involved in this study. RESULTS: No statistically significant correlation between pro MMP-2, pro MMP-9, VEGF and CA 15.3 serum levels was found (p>0.05). In breast cancer patients, a significant decrease of the pro MMP-2 serum expression 1 month after surgery with respect to serum levels before surgery (p=0.0008) was evident, as well as of CA 15.3 serum levels at baseline and after 1 month (p=0.017). Moreover a strong decrease of pro MMP-9 serum levels was found in 88 breast cancer patients after 1 month (p=0.028) and after 6 months (p =0.009) from surgery. On the other hand, no significant differences in the serum levels of VEGF, CA 15.3, pro MMP-2 or pro MMP-9 between 88 breast cancer patients preoperatively and 20 healthy women as controls were found. Our findings did indicate a significant positive association between higher preoperative levels of CA 15.3 and progression of disease (p=0.03), as well as a longer disease-free survival in patients who exhibited a decrease of serum pro MMP-9 expression compared to other biomarkers. No relationship between these four markers and the main clinical and pathological parameters was found. CONCLUSION: The present study failed to demonstrate any association between serum levels of MMPs, VEGF and CA 15.3 and well-known clinicopathological characteristics of breast carcinoma, while demonstrating the prognostic value of CA 15.3 and pro MMP-9 in the follow-up of breast cancer patients.

Influence of GBV-C infection on the endogenous activation of the IFN system in HIV-1 co-infected patients.

BACKGROUND: GB virus C (GBV-C) co-infection is associated with a better prognosis in HIV-infected persons. Since interferon activation can be one of the possible mechanisms involved in GBV-C-driven protection against HIV, we compared the endogenous activation of the interferon system in PBMC from GBV-C-positive and -negative patients infected with HIV-1. METHODS: The expression of interferon related genes was analyzed in 20 GBV-C positive and 20 GBV-C-negative HIV-infected patients, comparable in terms of CD4 cell counts and HIV viral loads. The levels of mRNA for interferon-related genes (2-5-OAS, MxA, interferon AR-1 and PKR) in PBMC were measured by real time RT-PCR, using B-actin as internal control. RESULTS: The endogenous levels of all the Interferon-related genes in HIV/GBV-C co-infected patients were higher than in HIV mono-infected subjects. The difference was statistically significant for PKR mRNA. Direct positive correlation was found between PKR and all the other interferon-related genes, suggesting a coordinated activation of the interferon system. CONCLUSIONS: Enhanced activation of the interferon system occurs in GBV-C-positive, as compared to GBV-C-negative patients harbouring HIV-1. These data may be relevant to understand the GBV-C-driven protection against HIV, suggesting that the endogenous activation of the interferon system can contribute to the control of HIV replication.

Clinical and prognostic role of matrix metalloproteinase-2, -9 and their inhibitors in breast cancer and liver diseases: A review.

Matrix metalloproteinases are a family of zinc endopeptidases with proteolytic activity against the extracellular matrix components. In particular, two members of this family named Gelatinase A and B, as amply documented in the literature, play a key role in the process of tumor growth/metastasis in breast and hepatocellular carcinoma. Their activity is regulated by Tissue Inhibitor of metalloproteinases-1 and -2, which are the physiological inhibitor of Gelatinases A and B respectively. The aim of this review is to determine the current understanding of the clinical and prognostic role of Metalloproteinases-2 and -9 and their inhibitors in the course of breast cancer and liver diseases. Forty-one articles were selected from PubMed by entering the following keywords: liver diseases, breast cancer, MMP-2, TIMP-2; all articles were read and notes were made regarding the number of enrolled patients, pathology, measures, results and these data were used to write this review. Over-expression of both gelatinases is associated with the relapse of disease, metastasis, shorter overall survival in breast cancer and hepatocellular carcinoma and invasion and progression to tumors in chronic liver diseases, and MMPs/TIMPs ratio could be useful in the follow-up of these patients.

Bone marrow CD34+ progenitor cells may harbour HIV-DNA even in successfully treated patients.

The issue about bone marrow hematopoietic progenitor cells harbouring HIV-DNA in infected patients is still under scrutiny. We studied nine HIV-infected individuals undergoing bone marrow aspiration for diagnostic purposes. In all patients, even in those receiving successful antiretroviral therapy for several years, HIV-DNA was detected in purified CD34+ lineage-bone marrow progenitor cells. This finding, although not conclusive due to the low number of patients examined, adds further evidence that current treatment strategies may be insufficient to resolve latent infection in bone marrow CD34+ hematopoietic progenitor cells.

Unidirectional budding of HIV-1 at the site of cell-to-cell contact is associated with co-polarization of intercellular adhesion molecules and HIV-1 viral matrix protein.

OBJECTIVES: To explore the possibility that HIV-1 budding and cellular adhesion molecules co-polarize at cell-to-cell contact sites. To investigate the incorporation of host-cell-derived adhesion molecules into HIV-1. METHODS: The cellular sites involved in HIV-1 budding were examined by transmission electron microscopy. Single and double immunocytochemistry staining was used to evaluate the cellular distribution of the viral matrix protein and adhesion molecules. Quantitative flow cytometry was used to measure the cellular expression of adhesion molecules. An immunocapture technique was used to measure the presence of cell-derived proteins on HIV-1. The captured virus was measured by a p24 antigen assay. The infectivity of virus captured by monoclonal antibodies was tested by measuring the virus antigen yield in supernatants after the addition of sensitive cells. RESULTS: Released and budding HIV-1 was mainly localized at the cell-to-cell contact regions. This feature was consistent with a polarized staining for the virus matrix protein p18 at cell-to-cell contact regions. Intercellular adhesion molecules (ICAM)-1 in HIV-1-infected cells were polarized on both isolated cells and syncytia, co-localizing with HIV-1 matrix protein. HIV-1 incorporated all the adhesion molecules expressed by the host cells, although without quantitative correlation with their cellular expression. CONCLUSIONS: HIV-1 is released at cell-to-cell membrane contact sites. Both ICAM-1 and virus matrix protein co-polarized on isolated cells and syncytia at the sites involved in the recruitment of uninfected cells. The impressive concentration of ICAM at cell sites where most virions are released may account for the acquisition of these membrane proteins by the HIV-1 progeny, and may be important for the cell-mediated spread.

Changes in host cell molecules acquired by circulating HIV-1 in patients treated with highly active antiretroviral therapy and interleukin-2.

OBJECTIVE: To analyse cell membrane proteins (CMP) acquired by HIV-1 present in the plasma of asymptomatic patients, and their modifications after a cycle of highly active antiretroviral therapy (HAART) and interleukin (IL)-2. DESIGN AND METHODS: Plasma samples from eight drug-naive asymptomatic subjects underwent immobilized antibody capture (IAC) to detect CMP on the surface of circulating HIV-1. The CMP considered were lymphocyte subset markers (CD45RA, CD45RO), activation markers (HLA-DR), adhesion molecules (LFA-3), costimulatory proteins (B7-2), lymph-node homing receptors (CD62L) and pro-apoptosis molecules (FasL). This analysis was repeated after one cycle of HAART + IL-2, after virus rebound. RESULTS: LFA-3, followed by CD45RO and HLA-DR, are the most represented CMP on the surface of circulating virions in naive asymptomatic patients; CD45RA, CD62L, B7-2 and FasL are detected only occasionally. After rebound, a significant reduction of CD45RO and HLA-DR, but not of LFA-3, is observed on virions, whereas CD45RA and CD62L, as well as other molecules, are not affected, remaining almost undetectable. CONCLUSIONS: Assuming that CMP on HIV-1 reflect the cellular origin of virions, activated T cells expressing CD45RO, HLA-DR, and LFA-3 may be the main source of HIV-1 in asymptomatic patients. After a cycle of HAART + IL-2, followed by therapy interruption, CD45RA and CD62L are detected on virions rarely, indicating that even during virus rebound, expanded naive T cells do not become a major target of virus replication. Furthermore, the presence of HLA-DR on rebound HIV-1 is decreased, consistent with decreased activation of the HIV-producing cells. More extensive investigation may clarify the significance of these findings with respect to pathogenesis.

RANTES stimulates cell-mediated transmission of HIV-1 infection.

We wished to determine the effects of the beta-chemokine RANTES in an established system of cell-mediated transmission of HIV-1, that is, normal human umbilical vein endothelial cells (HUVEC) nonproductively infected with HIV-1, cocultivated with CD4+ T cells to rescue productive infection. The results indicate that the addition of RANTES to HUVEC, either before or after HIV-1 infection, stimulates HIV-1 rescue by CD4+ T cells. However, viral DNA is not increased in HUVEC, suggesting that the stimulation exerted by RANTES could be mediated by events following HUVEC infection. The mechanisms of increase seem to be related to the rescue phase, involving membrane interaction of abortively infected HUVEC with permissive T cells. In fact, a strong upregulation and polarization of intercellular adhesion molecule-1 (ICAM-1) is induced in HUVEC by RANTES, and antibodies against ICAM-1 inhibit HIV-1 rescue by T cells. These results indicate that RANTES, similarly to other inflammatory cytokines, may favor HIV-1 spreading and crossing of blood-tissue barriers by indirect mechanisms involving membrane interactions between nonproductively infected and permissive cells.

Inhibition of HIV type 1 BaL replication by MIP-1alpha, MIP-1beta, and RANTES in macrophages.

The beta-chemokines RANTES, MIP-1alpha, and MIP-1beta have been shown to inhibit the infection of T cells by macrophage-tropic HIV-1 strains by blocking env-driven HIV-1 fusion through competition for the chemokine receptors or receptor downregulation. This study was aimed at testing whether beta-chemokines also inhibit the productive infection of monocyte-derived macrophages (MDMs) by a monocytotropic HIV-1 strain, by using virus yield assays. The action of the beta-chemokines MIP-1alpha, MIP-1beta, and RANTES was captured with that of the alpha-chemokine interleukin 8 (IL-8) and of interferon alpha (IFN-alpha), which is a well-known broad-range inhibitor of viral replication. While IL-8 did not inhibit HIV-1 BaL replication in MDMs, the beta-chemokines were dose-dependently inhibitory. RANTES was the most effective, reaching at 300 ng/ml a protection similar to that obtained with IFN-alpha at 1000 IU/ml, and was even more inhibitory when added to MDMs after virus attachment. In contrast to IFN-alpha, the antiviral activity of beta-chemokines was restricted to HIV, because another virus was not inhibited. As compared with untreated MDMs, full-length proviral DNA at day 1 postinfection was inhibited in MDMs treated with RANTES either before or after the absorption phase, and even more so in IFN-treated MDMs, whereas in IL-8-treated MDMs no inhibition was observed. Our results indicate that in MDMs both RANTES and IFN affect early steps of HIV-1 BaL replication, preceding the completion of viral DNA synthesis.

HIV type 1 grown on interferon gamma-treated U937 cells shows selective increase in virion-associated intercellular adhesion molecule 1 and HLA-DR and enhanced infectivity for CD4-negative cells.

Cellular adhesion molecules, such as ICAM-1, -2, and -3; LFA-1; and HLA class I and II are incorporated into HIV-1 virions during budding from infected cells. These virion-associated molecules can be involved in the adsorption to susceptible cells displaying the corresponding counterligands. A number of cytokines have been shown to upregulate the cellular expression of adhesion molecules, such as ICAM-1 and HLA-DR. In this study we investigated the effects of IFN-gamma on the incorporation of ICAM-1, LFA-1, and HLA-DR into mature HIV-1 progeny from chronically infected cells. The ability of such virus progeny to infect either CD4-positive or -negative cells was also investigated. The results indicate that IFN-gamma stimulates the expression of ICAM-1 and of HLA-DR on HIV-1-infected cells, whereas LFA-1 expression is unaffected. The same modifications were also observed on virus progeny, because specific MAbs to ICAM-1 and HLA-DR captured infectious HIV-1 from IFN-treated cells with higher efficiency as compared to virus from control cells, whereas virus binding to anti LFA-1 MAb was unchanged. Moreover, the HIV-1 progeny released from IFN-treated cells showed an increased ability to bind to and to infect CD4-negative cells, whereas the infectivity was basically unchanged for CD4-positive cells. Our results suggest that cytokines, as well as other soluble factors, may expand the host cell range of HIV-1, possibly through modifications of the cell-derived surface molecules on the virions.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of subcutaneous recombinant IL-2 on humoral immunity in advanced cancer-patients.

Immunotherapy represents a promising biological approach to cancer treatment. Important haemato-immunological modifications during rIL-2 treatment have been demonstrated in all patients treated, independently of the schedule and mode of rIL-2 administration. Generally, there is a lack of correlation between treatment-related modifications and clinical response. rIL-2 cell-mediated responses have been extensively studied but the role of humoral immunity is still unclear. We evaluated the peripheral blood CD4, CD8, CD19 and CD25 lymphocyte subset modifications and serum levels of immunoglobulin, IL-6 and IL-2 in 19 patients with malignant melanoma and renal cell carcinoma undergoing subcutaneous administration of IL-2. Our results suggest that humoral immunity is only marginally involved; however, the parameter variations observed suggest that further studies are necessary.

Cytokeratins and proliferation in breast cancer patients.

Tissue polypeptide antigen (TPA) was studied in 242 sera and 165 tumor cell cytosols (both evaluations in 67 cases) of breast cancer patients, for which proliferative activity, determined by the TLI technique, was also available. The TPA serum and tumor cell cytosol median values (utilized for measure analysis as cut-off) were 70 U/1 and 377 U/mg cytosol protein, respectively. High serum TPA levels were associated with unfavourable clinicopathological characteristics whereas a higher tumor cell cytosol TPA level was associated with better cytohistological tumor differentiation. Furthermore, no overall correlation was found between serum and tumor cell cytosol TPA levels or between their levels and TLI. When analyzing cases in which serum and tumor cell cytosol TPA values were higher than 100 U/l and 500 U/mg cytosol protein, respectively (n = 28), serum TPA was positively associated with TLI (slope = 12.3 r = 0.55, p < 0.01), while cytosolic TPA resulted negatively associated with TLI (slope = -87.4 r = 0.41, p < 0.01). Finally, a strong inverse relationship between cytosolic and serum TPA (p < 0.0005) became evident. We suggest that TPA could represent a serum marker for tumor cell proliferation in specific patient subgroups with original high serum and/or cytosol TPA expression.

Evaluation of phagocytic-activity in neoplastic patients treated with subcutaneous recombinant IL-2.

Immunostimulating and immunosuppresive events have been noted during rIL-2 immunotherapy and cell-mediated immune deficiencies have been reported in the neutrophil and monocyte functions, determining a high incidence of infections in patients during intravenous rIL-2 treatment. The phagocytic activity of monocytes/macrophages and granulocytes was evaluated in 10 advanced solid tumor patients treated with subcutaneous rIL-2. Several indirect parameters of phagocytosis were also considered, such as Neopterin, Beta2 microglobulin, IL-2 soluble receptor, and the C3 and C4 fractions of the complement system. A decreased phagocytosis was demonstrated after subcutaneous rIL-2 administration together with an increase of indirect parameters of granulocyte/macrophage activity. Therefore, cellular activation does not seem to correspond to actual phagocytosis which is probably due to IL-2-induced secondary cytokines or to rIL-2 inhibitory effects.

Subcutaneous ril-2 in advanced melanoma and kidney carcinoma.

The aim of the present study was to verify the efficacy and tolerability of a treatment protocol using subcutaneous administration of rIL-2. Eighteen patients with metastatic disease were treated: 10 with renal carcinoma and 8 with malignant melanoma. The drug was administered as follows: 9 million UI/mq twice daily for two days followed by 1.8 million UI/mq twice daily for five days/week for six consecutive weeks. Of the 15 patients evaluated for clinical response, all completed treatment without rIL-2 dose modifications. No complete response was obtained. One patient with malignant melanoma and 1 with renal carcinoma (13%) had partial response (soft tissue and lymph nodes respectively) which lasted 3 and 4 months. Six patients with renal carcinoma and 3 melanoma patients had stable disease (60%) which lasted 6 months (median). Toxicity was moderate and spontaneously reversing after stopping treatment. Haemato-immunological modifications and pharmacokinetic study of this modality of rIL-2 treatment were also examined.

Comparison of nuclear matrix protein 22 and bladder tumor antigen in urine of patients with bladder cancer.

Recently, two new tumor markers for bladder cancer have been introduced: NMP22 test and BTA TRAK assay. This study was designed to evaluate the urinary values of these two proteins using quantitative enzyme immunoassays in well microplates. Urine samples from 47 healthy subjects, 26 with benign genitourinary disorders and 109 patients with a histological diagnosis of bladder cancer were collected. The specificity, the positive predictive value, the negative predictive value and the efficiency were established for NMP 22 and BTA, and the cut off values were fixed at a specificity of 95% in the benign disease group (12 U/ml and 23 U/ml respectively). We observed a very high concordance between the two urinary tumor markers (73%), although the overall sensitivity of BTA in bladder cancer patients seems to be better than that of NMP22 (62% vs 54% respectively), especially in the superficial disease group (36% for BTA and 14% for NMP22).

Standard interleukin-2 (IL-2) and interferon-alpha immunotherapy versus an IL-2 and 4-epirubicin immuno-chemotherapeutic association in metastatic renal cell carcinoma.

BACKGROUND: Recombinant human interleukin-2 (IL-2) has a well-documented anti-tumor activity against RCC and has demonstrated a synergistic anti-tumor activity between doxorubicin and IL-2, thus providing better survival. This study investigated the toxicity and efficacy of the association between doxorubicin and IL-2, and interferon-alpha, and the immuno-chemotherapeutic association with IL-2 and 4-Epirubicin. PATIENTS AND METHODS: Patients with histologic evidence of metastatic or advanced RCC were randomized to receive either IL-2 + IFN-alpha (Arm A) or IL-2 + 4-Epi (Arm B). Arm A patients received IFN-alpha subcutaneously at doses of 3 million UI on days 1, 3 and 5 for 6 weeks. Arm B patients received 4-EPI at doses of 25 mg/m2 on days 1, 8, 15, 22, 29 and 36. Treatment cycles were repeated at 10 week intervals. RESULTS: Of 38 evaluable patients, we observed 2 complete responses, 2 partial responses, 1 minimal response, 1 mixed response, 21 stationary disease and 11 disease progressions. There was no significant difference in overall survival between the two groups. However in arm B, the median overall survival for responding patients was better than that of patients who experienced a disease progression. Performance status was the only predictive prognostic factor. CONCLUSIONS: Our analysis confirms the low response rate associated with IL-2 treatments but seems to indicate a role of anthracycline in improving the survival of responding patients with an acceptable toxicity.

Serum 90K/MAC-2BP glycoprotein levels in hepatocellular carcinoma and cirrhosis.

90K/MAC-2BP glycoprotein is a serum tumour marker, member of the scavenger receptor cysteine rich (SRCR) protein superfamily, involved in different immunological mechanisms. In the present study, we determined 90K serum levels by a sandwich enzyme immunoassay using the same monoclonal antibody in 11 chronic active hepatitis (CAH), 48 liver cirrhosis and 36 hepatocellular carcinoma (HCC). In comparison, the same samples were also tested for AFP. According to a cut-off point of 14 micrograms/mL for the 90K, established as 100% of specificity in 50 controls, we observed increasing positivities from CAH to cirrhosis and then to HCC (27%, 50% and 78%, respectively). In cirrhotic patients 90K levels were associated with the presence of anti-HCV antibodies, but not with the degree of liver compromise. Finally, 90K sensitivity was higher than AIFP in all groups of hepatic patients. However, further investigations are needed before proposing 90K as a clinical useful tumour marker in the progression from cirrhosis to HCC.