Insulin-like growth factor (IgF)-I,IgF binding protein-3, and prostate cancer: correlation with gleason score

Introduction

Non-androgenic growth factors are involved in the growth regulation of prostate cancer (PCa).

Objective

This is the first Brazilian study to correlate, in a population of patients operated for PCa, PSA, total testosterone, insulin-like growth factor-I (IGF-I) and insulin-like growth factor-binding protein-3 (IGFBP-3) with Gleason score and to compare with a control group with benign prostate hyperplasia (BPH).

Materials and Methods

This retrospective single-center study included 49 men with previously diagnosed PCa and 45 with previously diagnosed BPH. PSA, testosterone, IGF-I, IGFBP-3 were determined in both groups.

Results

PSA and IGFBP-3 levels were significantly higher in the PCa group as compared to the BPH group (p<0.001 and p=0.004, respectively). There was a significant difference when we compared the PSA before surgery (p<0.001) and at the inclusion in the study (p<0.001) and IGFBP3 (0.016) among patients with Gleason <7, ≥7 and BPH. In the PCa group, PSA, testosterone, IGF-I and IGFBP-3 levels were comparable between Gleason <7 and ≥7.

Conclusions

Our data suggest that in localized PCa, the quantification of PSA and, not of IGF-1, may provide independent significant information in the aggressiveness. IGFBP-3 could be a biochemical marker of disease control in PCa patients.     

Sclerosing Paraganglioma of the Carotid Body: A Potential Pitfall of Malignancy

Paragangliomas (PGs) of the head and neck region are typically benign, slow-growing neuroendocrine tumours. At times, they may exhibit unusual histological features, such as prominent stromal sclerosis (sclerosing PG), which may raise concerns of malignancy. We describe a case of sclerosing PG of the carotid body, emphasizing the value of immunohistochemical stains for differential diagnosis. A 43-year-old woman presented with a painless lump on the neck. A magnetic resonance imaging scan demonstrated a hypervascular lesion of the carotid body, which was surgically excised. Grossly, the lesion measured 1.8 cm at maximum diameter. On microscopic examination, irregular nests and tiny bundles of neoplastic cells were found between thick bands of fibrous tissue. Focal nuclear cytomegaly and marked pleomorphism were noted. Neoplastic cells proved to be immunoreactive for chromogranin, synaptophysin and neuron specific enolase, but negative for cytokeratins, smooth muscle actin and CD34. Ultrastructurally, numerous mitochondria, rough endoplasmic reticulum structures and endocrine granules were seen in the cytoplasm of the tumour cells. On consideration of the above-mentioned clinico-pathological and ultrastructural findings a diagnosis of sclerosing PG was established. Sclerosing PG is a rare entity which may mimic a malignant neoplasm. The recognition of this unusual morphological variant of PG, together with appropriate immunostains, leads to the correct diagnosis.     

IL-4 in vitro production is upregulated in Alzheimer's disease patients treated with acetylcholinesterase inhibitors

Cytokines appear to be involved in the pathogenesis of Alzheimer's Disease (AD). Their modulation by treatment has been investigated only in a few studies. The aim of our study was to evaluate the effect of acetylcholinesterase inhibitors (AChEI) on Interleukin-4 (IL-4) production in AD patients. IL-4 levels were measured by ELISA on peripheral blood mononuclear cell cultures in the presence or absence of Concanavalin A or Phytohaemagglutinin. Linear regression analysis shows that patients who have been treated, have higher levels of IL-4 independently from age, gender and comorbidity. The increased production of IL-4 in AChEI treated patients might represent an additional mechanism through which AChEI act on AD progression.     

Neoplastic conditions in the context of HIV-1 infection

HIV-1 infection predisposes to the development of specific types of cancer. Most cancers seen in the AIDS setting are related to oncogenic virus infections, such as Epstein-Barr virus (EBV), Kaposi's sarcoma (KS)-associated herpesvirus (KSHV) and human papillomavirus (HPV). It is generally assumed that HIV-1 infection play a passive role in cancer development by impairing the host immune surveillance and increasing the risk of oncogenic virus infection. Recent insights, however, indicate that HIV-1 infection more actively promotes cancer growth. Experimental evidence has shown that HIV-1-encoded proteins can directly induce tumor angiogenesis and enhance KSHV transmission to target cells. Clinical evidence suggests that the oncogenicity of HPV is altered by the presence of HIV-1 infection irrespective of host immune status. The introduction of highly active antiretroviral therapy (HAART) has dramatically decreased the incidence of KS whereas the impact of HAART is variable in EBV-related lymphoma and HPV-related cervical cancer, suggesting that additional factors are involved in the pathogenesis of these cancers. Understanding the direct and indirect roles of HIV-1 in the pathogenesis of neoplastic conditions could provide the rationale for prevention and development of new treatments for AIDS-associated malignancies.     

Effect of hepatitis B and C virus infections on the natural history of compensated cirrhosis: a cohort study of 297 patients

OBJECTIVES: The aim of this study was to compare the prognosis of patients with hepatitis B surface antigen (HBsAg) positive and those with antibody to hepatitis C (anti-HCV) positive cirrhosis. METHODS: This was a retrospective cohort study of 297 untreated Western European patients with compensated viral cirrhosis (Child class A; 161 patients with hepatitis type B and 136 with type C) who were followed for a median period of 6.6 yr. RESULTS: At diagnosis, median age was lower (48 vs 58 yr, respectively) in HBsAg-positive cirrhotic patients. The Kaplan-Meier 5-yr probability of hepatocellular carcinoma (HCC) was 9% and 10% in HBsAg and anti-HCV-positive cirrhotic patients, respectively; the corresponding figures for decompensation unrelated to HCC were 16% and 28% and for survival were 86% and 84%, respectively. After adjustment for clinical and serological differences at baseline, the relative risk (95% CI) for HCC, decompensation and mortality was 1.53 (CI = 0.81-2.89), 0.59 (CI = 0.37-0.94), and 1.44 (CI = 0.85-2.46) respectively, in HBsAg-positive patients compared with anti-HCV-positive cirrhotic patients. Among HBsAg-positive cirrhotic patients, the relative risk for HCC, decompensation, and mortality was 0.89 (CI = 0.30-2.63), 4.05 (CI = 1.09-15.1), and 5.9 (CI = 1.64-21.3), respectively, in HBV-DNA positive (HBeAg positive or negative) compared with HBV-DNA negative (HBeAg negative) patients at entry. CONCLUSIONS: Patients with HBV infection may present with cirrhosis about 10 yr earlier than those with HCV infection. HCV infection tends to be associated with a higher risk of decompensation, but these data should take into consideration the heterogeneity of HBV-related cirrhosis in terms of viremia levels and risk of hepatic failure. Survival shows no significant differences according to HBV or HCV etiology in Western European cirrhotic patients.     

Identification of carboxypeptidase N as an enzyme responsible for C-terminal cleavage of stromal cell-derived factor-1alpha in the circulation

The chemokine stromal-derived factor-1alpha (SDF-1alpha) is an essential regulator of hematopoiesis, lymphocyte homing, pre-B-cell growth, and angiogenesis. As SDF-1alpha is constitutively expressed in many tissues, chemokine function is mostly regulated by proteolytic degradation. Human serum cleaves the 68-amino acid chemokine, SDF-1alpha, at both termini. The enzyme or enzymes responsible for the removal of the carboxy-terminal lysine from SDF-1alpha, leading to significant reduction in biologic activity, have not been identified. Using a new biochemical assay for measuring the carboxy-terminal cleavage activity, we purified from serum and plasma a peptidase that specifically removes the carboxy-terminal lysine from SDF-1alpha and identified it as carboxypeptidase N (CPN, also known as kininase I, arginine carboxypeptidase, and anaphylotoxin inactivator). We demonstrate that SDF-1alpha in serum and plasma lacks the carboxy terminal lysine, and depletion of CPN from serum and plasma significantly reduces the SDF-1alpha carboxypeptidase activity. Purified CPN effectively and specifically removes the carboxy-terminal lysine from SDF-1alpha and significantly reduces the chemokine's biologic activity as a pre-B-cell growth factor and chemoattractant. Thus, in addition to its role as a regulator of the biologic activity of kinins and anaphylatoxins, CPN is an important regulator of the biologic activity of SDF-1alpha by reducing the chemokine-specific activity.     

A torque-measuring micromotor provides operator independent measurements marking four different density areas in maxillae

PURPOSE

Bone density at implant placement site is a key factor to obtain the primary stability of the fixture, which, in turn, is a prognostic factor for osseointegration and long-term success of an implant supported rehabilitation. Recently, an implant motor with a bone density measurement probe has been introduced. The aim of the present study was to test the objectiveness of the bone densities registered by the implant motor regardless of the operator performing them.

MATERIALS AND METHODS

A total of 3704 bone density measurements, performed by means of the implant motor, were registered by 39 operators at different implant sites during routine activity. Bone density measurements were grouped according to their distribution across the jaws. Specifically, four different areas were distinguished: a pre-antral (between teeth from first right maxillary premolar to first left maxillary premolar) and a sub-antral (more distally) zone in the maxilla, and an interforaminal (between and including teeth from first left mandibular premolar to first right mandibular premolar) and a retroforaminal (more distally) zone in the lower one. A statistical comparison was performed to check the inter-operators variability of the collected data.

RESULTS

The device produced consistent and operator-independent bone density values at each tooth position, showing a reliable bone-density measurement.

CONCLUSION

The implant motor demonstrated to be a helpful tool to properly plan implant placement and loading irrespective of the operator using it.     

Annexin A1–containing extracellular vesicles and polymeric nanoparticles promote epithelial wound repair

Epithelial restitution is an essential process that is required to repair barrier function at mucosal surfaces following injury. Prolonged breaches in epithelial barrier function result in inflammation and further damage; therefore, a better understanding of the epithelial restitution process has potential for improving the development of therapeutics. In this work, we demonstrate that endogenous annexin A1 (ANXA1) is released as a component of extracellular vesicles (EVs) derived from intestinal epithelial cells, and these ANXA1-containing EVs activate wound repair circuits. Compared with healthy controls, patients with active inflammatory bowel disease had elevated levels of secreted ANXA1-containing EVs in sera, indicating that ANXA1-containing EVs are systemically distributed in response to the inflammatory process and could potentially serve as a biomarker of intestinal mucosal inflammation. Local intestinal delivery of an exogenous ANXA1 mimetic peptide (Ac2-26) encapsulated within targeted polymeric nanoparticles (Ac2-26 Col IV NPs) accelerated healing of murine colonic wounds after biopsy-induced injury. Moreover, one-time systemic administration of Ac2-26 Col IV NPs accelerated recovery following experimentally induced colitis. Together, our results suggest that local delivery of proresolving peptides encapsulated within nanoparticles may represent a potential therapeutic strategy for clinical situations characterized by chronic mucosal injury, such as is seen in patients with IBD.     

Accurate estimate of pancreatic T2* values: how to deal with fat infiltration

Purpose

We examined different approaches aimed to deal with the signal fluctuation of pancreatic T2* values due to fat infiltration in order to obtain accurate estimates of iron overload.

Methods

Pancreatic T2* values were assessed in 20 patients (13 females, 37.24 ± 9.12 years) enrolled in the Myocardial Iron Overload in Thalassemia network without and with the application of fat suppression-FS (T2*-NoFS and T2*-FS). T2* values were assessed in three different ways: (1) from the immediate fit (original T2*); (2) discarding the echoes until the achievement of a good visual concordance between the signal and the model (final_vis T2*); (3) eliminating the echoes until the achievement of a fitting error (known) <5% (final_thres T2*).

Results

For the T2*-NoFS sequence the original T2* values were significantly higher than the final_vis T2* values (difference:4.8 ± 6.1 ms; P < 0.0001) and the final_thres T2* values (difference:4.3 ± 6.1 ms; P = 0.006). For the T2*-FS sequence the original T2* values were comparable to final_vis and final_thres T2* values. The original T2*-FS values were significantly different from the original T2*-NoFS values. The final_vis T2*-FS values were comparable to the final_vis T2*-NoFS values and the final_thresh T2*-FS values were comparable to the final_thresh T2*-NoFS values. For both T2*-FS and T2*-NoFS sequences, the final_thres T2* values were not significantly different from the final_vis T2* values and no bias was present.

Conclusions

In the clinical practice, an accurate pancreatic iron overload assessment should be done by applying FS and, when needed, by discarding the TEs until the fitting error goes below 5%.