Angiotensin AT4 ligands are potent, competitive inhibitors of insulin regulated aminopeptidase (IRAP)

Angiotensin IV (Ang IV) exerts profound effects on memory and learning, a phenomenon ascribed to its binding to a specific AT4 receptor. However the AT4 receptor has recently been identified as the insulin-regulated aminopeptidase (IRAP). In this study, we demonstrate that AT4 receptor ligands, including Ang IV, Nle1-Ang IV, divalinal-Ang IV, and the structurally unrelated LVV-hemorphin-7, are all potent inhibitors of IRAP catalytic activity, as assessed by cleavage of leu-β-naphthylamide by recombinant human IRAP. Both Ang IV and divalinal–Ang IV display competitive kinetics, indicating that AT4 ligands mediate their effects by binding to the catalytic site of IRAP. The AT4 ligands also displaced [125I]-Nle1-Ang IV or [125I]-divalinal1-Ang IV from IRAP-HEK293T membranes with high affinity, which was up to 200-fold greater than in the catalytic assay; this difference was not consistent among the peptides, and could not be ascribed to ligand degradation. Although some AT4 ligands were subject to minor cleavage by HEK293T membranes, none were substrates for IRAP. Of a range of peptides tested, only vasopressin, oxytocin, and met-enkephalin were rapidly cleaved by IRAP. We propose that the physiological effects of AT4 ligands result, in part, from inhibition of IRAP cleavage of neuropeptides involved in memory processing.

An approach to faulty reader detection in RFID reader network

Radio Frequency Identification (RFID) technology is becoming increasingly popular as an automated tool for object monitoring and identification in a cost-efficient manner. RFID systems are made up of heterogeneous components consisting of both hardware and software. RFID components such as the readers are prone to failures with serious consequences to the overall system. Thus, issues such as reliability and dependability of RFID systems are receiving attention recently. This mandates fault management that includes monitoring the health of RFID readers and accessing the RFID reader configurations remotely. Therefore, an approach that detects the faulty readers with the aim to minimize the impacts of the faulty readers on the system reliability and dependability is of paramount importance. In this chapter, the authors discuss an approach to detect faulty readers in networked RFID system environments. Performance evaluation of the approach against other techniques is presented and shows that it performs reasonably well in the presence of faulty readers.

A security framework for networked RFID

In the last decade RFID technology has become a major contender for managing large scale logistics operations and generating and distributing the massive amount of data involved in such operations. One of the main obstacles to the widespread deployment and adoption of RFID systems is the security issues inherent in them. This is compounded by a noticeable lack of literature on how to identify the vulnerabilities of a RFID system and then effectively identify and develop counter measures to combat the threats posed by those vulnerabilities. In this chapter, the authors develop a conceptual framework for analysing the threats, attacks, and security requirements pertaining to networked RFID systems. The vulnerabilities of, and the threats to, the system are identified using the threat model. The security framework itself consists of two main concepts: (1) the attack model, which identifies and classifies the possible attacks, and (2) the system model, which identifies the security requirements. The framework gives readers a method with which to analyse the threats any given system faces. Those threats can then be used to identify the attacks possible on that system and get a better understanding of those attacks. It also allows the reader to easily identify all the security requirements of that system and identify how those requirements can be met.

The need to examine metastatic tissue at the time of progression of breast cancer : is re-biopsy a necessity or a luxury?

Knowledge of estrogen receptor (ER), progesterone receptor (PgR) and human epidermal growth factor receptor-2 (HER2) status is necessary for determining the optimal treatment of breast cancer patients. At the same time, the discordance between marker profiles (ER/PR and HER2) of primary and metastatic breast cancer is well documented. Whether discordant cases are secondary to “clonal selection” in the face of targeted anti-estrogen or anti-HER2 therapy or whether they are a laboratory artifact is still debated; both scenarios are likely. This article outlines current modalities for ER, PR, and HER2 testing in primary breast carcinoma and its metastases and reviews prospective and retrospective studies that have addressed these issues, as well as recent advances in the field.

Thrombocytopenia in solid tumors

Thrombocytopenia in patients with solid malignancy can be caused by bone marrow involvement or toxicity from anticancer therapy; however, it could rarely be the first presentation of a tumor such as breast cancer or lymphoma. Hematological paraneoplastic syndromes such as paraneoplastic thrombocytopenia and/or immune thrombocytopenic purpura (ITP) are well described as secondary findings simultaneously with malignancies such as breast cancer and lymphoma. Other hematological conditions such as severe amegakaryocytic thrombocytopenia, thrombotic thrombocytopenic purpura (TTP), and myelodysplastic syndromes (MDS) have also rarely been described as a possible paraneoplastic process complicating solid tumors. On the one hand, occult disseminated malignancy may mimic ITP and TTP, leading to diagnostic and therapeutic problems. On the other hand, thrombocytopenia could be the first manifestation of cancer.

Management of advanced neuroendocrine tumors with hepatic metastasis

Neuroendocrine tumors (NETs) in general and specifically these gastroenteropancreatic-neuroendocrine tumors often present a considerable diagnostic and therapeutic challenge, especially those that behave in an aggressive fashion. The majority of tumors are diagnosed at a stage that the only curative treatment, radical surgical intervention, is no longer an option and thus long-term therapy with somatostatin analogs is focused on symptom amelioration and in the improvement of quality of life. Although biotherapy is currently the most efficient treatment to achieve palliation, conventional chemotherapy may have some utility in undifferentiated or highly proliferating neuroendocrine carcinomas and pancreatic NETs. Hepatic metastases, depending on size, location, and number may be amenable to surgical resection or radiofrequency ablation. If surgery is not feasible, embolization either alone (bland), in combination with chemotherapeutic agents, or using radioactive microspheres can be used. Peptide receptor targeted radiotherapy using radiolabeled octapeptide analogs (⁹⁰Yttrium or ¹⁷⁷Lutetium-octreotide) may lead to reduction in tumor size, but in most circumstances has a tumor stabilizing effect. A variety of antiangiogenesis and growth factor-targeted agents have been evaluated, but to date, the results have failed to meet our expectations.

Anti-angiogenic therapy for high grade glioma

This is the protocol for a review and there is no abstract. The objectives are as follows:

To evaluate the efficacy and toxicity of anti-angiogenic therapy, either alone or in combination with chemotherapy and/or radiotherapy in patients with HGG. Comparisons will be as follows:

1. Newly diagnosed HGG treated with radiotherapy and chemotherapy in combination with angiogenesis inhibitor versus without angiogenesis inhibitors.
2. First relapse therapy with angiogenesis inhibitor versus without angiogenesis inhibitors.
3. Second or third line angiogenesis inhibitors versus therapy without angiogenesis inhibitors.

Neuro-oncology : late neurocognitive decline after radiotherapy for low-grade glioma

Radiotherapy is administered to most patients with low-grade glioma. A well-designed, retrospective study assessed neurocognitive function in patients who had received radiotherapy for low-grade gliomas versus those who had not. Cognitive function did not differ markedly between groups after 6 years, but by 12 years this feature was worse in the group that received radiotherapy.

Advances in the treatment of malignant gliomas

Local control with surgery, radiation, and temozolomide chemotherapy remain the pillars of treatment for high-grade gliomas. Novel therapeutic strategies, including a variety of antiangiogenic agents, are under investigation. One of these agents, bevacizumab, was recently given accelerated approval by the US Food and Drug Administration as a single agent for recurrent glioblastoma. Recent trial results are generating important clinical questions regarding which patients to treat and when, and how best to monitor response. Encouraging results of recent studies are driving willingness to undertake aggressive treatment and to improve outcomes in this population. In this era, better understanding of biology, molecular aspects of cancer, and clinical trial methodology are crucial for clinicians. This review focuses on recent advances in the treatment malignant gliomas, especially antiangiogenic therapy.

Chemotherapy in the elderly

The number of elderly patients with malignancy is growing and is likely to have a major impact on resources, quality of care, health economics and treatment options. Decisions regarding treatment options with chemotherapy are limited by the scarcity of data specifically addressing the issues regarding chemotherapy in the elderly. The problem is further confounded by issues such as co morbidity, poly-pharmacy, cognitive impairments, emotional problems, functional limitations, sensory impairment and a lack of social support. Ageing is associated with specific physiologic changes in functional status, organ function and drug pharmacokinetics. Optimising cancer care and chemotherapy delivery in the elderly requires a better understanding of the specific pharmacokinetic and pharmacodynamic issues and administration of chemotherapy in this age group. Elderly participation in clinical trials and specific research is essential to guide treatment decisions and further research is required to provide evidence-based models to guide treatment decisions. In an Australian setting, the development of a geriatric oncology specific group as a means of facilitating collaboration with geriatricians, development of specific elderly research programs and clinical trials, education and development of treatment guidelines would further improve outcomes of our elderly patients undergoing cancer treatment.