Cancer immunotherapy and heat-shock proteins: promises and challenges

Recent mechanistic studies on the role of heat-shock proteins (HSPs) to induce innate and adaptive immune responses have resulted in conflicting reports. Whereas some groups reported that HSPs have direct immunological function, others emphasised the endotoxin contamination of HSP preparations and questioned the antigen-specificity of HSP vaccines. The present review will discuss these issues and suggest that HSPs have diverse and distinct immunological functions that could be superimposed on effects resulting from endotoxin contamination or misunderstood by using experimental procedures with inadequate controls. To understand the actual function of HSPs in their interaction with the immune system, methods and procedures need to be optimised and appropriate controls need to be used. These points should also clarify the conflicting findings about HSPs and promote our knowledge about other immuologically important components that may be present in HSP preparations.     

The effects of vascular bed expansion in steatotic rat liver graft viability

Disturbed microcirculation caused by fat accumulation in hepatocytes has been implicated in poor graft preservation and reperfusion. The aim of this study was to investigate the effect of vascular bed expansion (VBE) during cold preservation in graft survival Moderate liver steatosis in male Wistar rats (240–280 g) was induced by choline-deficient diet. Normal, steatotic or VBE-pretreated steatotic grafts were transplanted after 1 h or 9 h of cold preservation. Graft viability was determined by 7-day survival, serum liver enzymes, plasma tumour necrosis factor (TNF)-, interleukin (IL)-6, and malondialdehyde (MDA) levels. Post-reperfusion bile flow and liver histology were also examined. After 9 h of preservation, VBE-pretreated steatotic liver grafts were associated with significantly reduced serum liver enzyme, plasma TNF-, IL-6, and MDA levels, as well as increased bile flow and higher survival rates compared with untreated ones. The present study shows that VBE protects fatty liver grafts from subsequent long-term cold preservation and reperfusion injury in a rat liver transplantation model.     

Rhinoorbital mucormycosis secondary to Rhizopus oryzae: a case report and literature review

Mucormycosis is a form of fulminant invasive fungal infection of the sinonasal tract that often extends to the orbit, brain, palate, and skin. It is caused by members of the order Mucorales, and it is considered to be the most fatal fungal infection known to man because it is rapidly disseminated by the blood vessels. It is most commonly associated with diabetic ketoacidosis, hematologic malignancies, acquired immunodeficiency syndrome, and immunosuppressive therapy. This rare opportunistic infection exists in many forms, the most common of which is rhinocerebral mucormycosis. Treatment includes aggressive surgical debridement of the necrotic tissue combined with systemic antifungal therapy. In this case report, we describe the successful management of rhinoorbital mucormycosis, a subtype of the rhinocerebral variety, secondary to Rhizopus oryzae that developed in a patient with lymphoma. We review the diagnostic work-up and discuss the literature with respect to the presentation, pathophysiology, management, and outcome of the disease.     

T-cell-rich B-cell lymphoma: a clinicopathologic study of 21 cases and comparison with 43 cases of diffuse large B-cell lymphoma

Clinicopathologic features of 21 patients with T-cell-rich B-cell lymphoma (TCRBCL) were reviewed and compared to 43 patients with diffuse large B-cell lymphoma (DLBCL) to determine if there were distinguishing clinical characteristics and differences in response or survival to CHOP therapy. For the diagnosis of TCRBCL, the current WHO criteria was used. In all of our cases, the majority of cells are non-neoplastic T cells and <10% large neoplastic B cells are present. The initial pathologic diagnosis was nodular lymphocyte predominant Hodgkin's lymphoma (NLPHL) in two cases. Patients with TCRBCL were significantly younger (median: 46 years) and had a significantly higher incidence of B symptoms (62%), hepatomegaly (33%) and marrow infiltration (33%) at presentation when compared to DLBCL (P<0.03). The CR rate after treatment was 48% for TCRBCL patients versus 79% for the DLBCL (P<0.003). Although the CR rates in between the two groups are significant, the difference in 3 years survival rates in each CR groups was insignificant (80% versus 77%). The overall survival time in the two groups was 17 months. Event-free survival time in TCRBCL was 12 months, compared with 17 months in the DLBCL (P>0.05). The frequency of patients with TCRBCL achieving CR was 52.6% whereas that of patients with DLBCL was 79% (P<0.003). The TCRBCL 3 years event-free survival 48% and overall survival 64% were 63 and 72% for DLBCL, respectively.     

Serum bcl-2 and survivin levels in melanoma

This study was conducted to investigate the serum levels of bcl-2 and survivin in patients with melanoma and the relationship with tumour progression and known prognostic parameters. Forty-four patients with cutaneous melanoma were investigated. Serum samples were obtained on first admission before adjuvant and metastatic treatment were given and at follow-up. Serum bcl-2 and survivin levels were determined using enzyme immunometric assay (EIA) and enzyme-linked immunosorbent assay (ELISA). The baseline serum bcl-2 levels were significantly higher in patients with melanoma than in the control group (P=0.01). For the serum survivin levels, no difference was found (P=0.6). No significant correlations were found between the prognostic parameters analysed and the serum survivin concentrations. The same was true of the serum bcl-2 values, except for the age of the patient (P=0.025) and nodal involvement (P=0.003). No significant relationship was found between the serum levels of bcl-2 and survivin (r=-0.13, P=0.4). In node-positive patients (n=8) both of these anti-apoptotic substances were unchanged after interferon-alpha-2b therapy. However, serum survivin concentrations were significantly increased in 10 patients with metastatic melanoma who underwent dacarbazine (DTIC)-based cytotoxic chemotherapy (P=0.047). A similar finding was not determined for the serum bcl-2 levels. In conclusion, the results of this study suggest that decreased apoptosis is associated partly with an increase in serum bcl-2. However, much research continues in this field, and exciting new knowledge will ultimately emerge.     

Therapeutic angiogenesis using autologous bone marrow stromal cells: improved blood flow in a chronic limb ischemia model

BACKGROUND: We evaluated the effect of autologous marrow stromal cells (MSCs) on neovascularization and blood flow in an animal model of chronic limb ischemia. METHODS: Chronic hind limb ischemia was created by ligating the left common iliac artery of male Lewis rats. Three weeks after ligation, 5.0 million LacZ+MSCs (n = 10) or culture medium (n = 10) were injected into the anteromedial muscle compartment of the left thigh. At 4 and 6 weeks after injection, half the animals (n = 5) from each group underwent femoral artery ultrasonic blood flow measurements of the ischemic and nonischemic limbs to obtain a flow ratio. The animals also underwent angiography and measurements of blood vessel density and arteriolar density. Qualitative histologic assessment of the limb muscles was performed. RESULTS: LacZ+MSCs were found to differentiate into endothelium (F VIII+), vascular smooth muscle (positive a-smooth muscle actin), skeletal muscle (positive desmin), and adipocytes. Ischemic hind limbs where MSCs were implanted had greater vascular density and arteriolar density than control limbs (p < 0.001). Femoral artery flow index (left femoral artery flow/right femoral artery flow) was 0.89 +/- 0.12 and 0.90 +/- 0.06 for rats injected with MSCs measured at 4- and 6-weeks, respectively, compared with 0.50 +/- 0.15 and 0.50 +/- 0.10 for the control rats (p < 0.001). Angiography demonstrated reconstitution of the left femoral artery in rats that received MSC implantation through pelvic and abdominal wall collateral formation. CONCLUSIONS: Local MSC implantation induces a neovascular response resulting in a significant increase in blood flow to the ischemic limb. Marrow stromal cells are also capable of spontaneously regenerating the various components of muscular tissues.     

Investigation of acute toxicity of deltamethrin on guppies (Poecilia reticulata)

Deltamethrin, a synthetic pyrethroid pesticide contaminating aquatic ecosystems as a potential toxic pollutant, was investigated in the present study for acute toxicity. Guppy fish (Poecilia reticulata) were selected for the bioassay experiments. The 48-h LC50 was determined for the guppies. The experiments were repeated three times and a total of 210 guppies were used. The static test method of acute toxicity test was used. In addition, behavioral changes at each deltamethrin concentration were determined for the individuals. Data obtained from the deltamethrin acute toxicity tests were evaluated using the Probit Analysis Statistical Method. The 48-h LC50 value for guppy was estimated as 5.13 microg/L.