Reply: Is CD1a involved in antitumour immune responses during carcinogenesis?

© 2004 Cancer Research UKPresents a response by the authors to a letter to the editor about their article "Is CD1a involved in antitumour immune responses during carcinogenesis?," published in the February 23, 2004 issue of the "British Journal of Cancer"B.J. Coventry and S. Heinze

The Design and Stability of Masonry Dams.

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Language and memory for object location

In three experiments, we investigated the influence of two types of language on memory for object location: demonstratives (this, that) and possessives (my, your). Participants first read instructions containing demonstratives/possessives to place objects at different locations, and then had to recall those object locations (following object removal). Experiments 1 and 2 tested contrasting predictions of two possible accounts of language on object location memory: the Expectation Model (Coventry, Griffiths, & Hamilton, 2014) and the congruence account (Bonfiglioli, Finocchiaro, Gesierich, Rositani, & Vescovi, 2009). In Experiment 3, the role of attention allocation as a possible mechanism was investigated. Results across all three experiments show striking effects of language on object location memory, with the pattern of data supporting the Expectation Model. In this model, the expected location cued by language and the actual location are concatenated leading to (mis)memory for object location, consistent with models of predictive coding (Bar, 2009; Friston, 2003)

Isolated limb infusion chemotherapy for melanoma: an overview of early experience at the Adelaide Melanoma Unit

Background: Isolated limb infusion (ILI) using cytotoxic agents has been demonstrated to be an effective and less invasive alternative modality than isolated limb perfusion for the treatment of melanoma localized to a limb. Percutaneous catheters were inserted into the axial artery and vein of the affected limb while using a pneumatic cuff to restrict limb vascular flow proximally to "isolate" the limb from the body and enable delivery of high-dose intra-arterial chemotherapy selectively to the limb. The ILI technique was developed at the Sydney Melanoma Unit (now renamed the Melanoma Institute Australia), and only a few other centers have reported separate results. We report our early results using the ILI technique for management of locally recurrent surgically nonresectable melanoma. Methods and results: Twenty-eight ILI procedures were performed in 20 patients treated with one or more procedures between 1997 and 2007. Patient parameters and clinical responses were evaluated. The median follow-up duration was 15.9 months after the first ILI, with an overall response rate after one or more infusions of 70%, of which 35% were complete responders and 35% were partial responders, with a further 20% showing stable disease, giving a "clinically significant" response rate of 90%. After one ILI (n = 20), the overall response rate was 70%, with 20% complete responders and 50% partial responders, and 20% with stable disease. Low limb toxicities were generally observed, and no amputations were required. Conclusion: ILI chemotherapy is a useful technique, which can be readily repeated for control of melanoma in the limb. It is generally well tolerated, and is capable of achieving a cure, delayed progression, or effective palliation in selected cases. The longest survivors in this series were 8 and 10 years from the last ILI.Mitchell H Giles, Brendon J Coventr

The 20th anniversary of interleukin-2 therapy: Bimodal role explaining longstanding random induction of complete clinical responses

Background: This year marks the twentieth anniversary of the approval by the US Food and Drug Administration of interleukin-2 (IL2) for use in cancer therapy, initially for renal cell carcinoma and later for melanoma. IL2 therapy for cancer has stood the test of time, with continued widespread use in Europe, parts of Asia, and the US. Clinical complete responses are variably reported at 5%–20% for advanced malignant melanoma and renal cell carcinoma, with strong durable responses and sustained long-term 5–10-year survival being typical if complete responses are generated. Methods: The literature was reviewed for the actions and clinical effects of IL2 on subsets of T cells. The influence of IL2 on clinical efficacy was also sought. Results: The review revealed that IL2 is capable of stimulating different populations of T cells in humans to induce either T effector or T regulatory responses. This apparent "functional paradox" has confounded a clear understanding of the mechanisms behind the clinical effects that are observed during and following administration of IL2 therapy. An average complete response rate of around 7% in small and large clinical trials using IL2 for advanced renal cell carcinoma and malignant melanoma has been shown from a recent review of the literature. Conclusion: This review considers the published literature concerning the actions and emerging clinical effects of IL2 therapy, spanning its 20-year period in clinical use. It further details some of the recently described "bimodal" effects of IL2 to explain the apparent functional paradox, and how IL2 might be harnessed to emerge rapidly as a much more effective and predictable clinical agent in the near future.Brendon J Coventry, Martin L Ashdow

Cued by What We See and Hear: Spatial Reference Frame Use in Language

To what extent is the choice of what to say driven by seemingly irrelevant cues in the visual world being described? Among such cues, how does prior description affect how we process spatial scenes? When people describe where objects are located their use of spatial language is often associated with a choice of reference frame. Two experiments employing between-participants designs (N = 490) examined the effects of visual cueing and previous description on reference frame choice as reflected in spatial prepositions (in front of, to the left of, etc.) to describe pictures of object pairs. Experiment 1 examined the effects of visual and linguistic cues on spatial description choice through movement of object(s) in spatial scenes, showing sizeable effects of visual cueing on reference frame choice. Experiment 2 monitored eye movements of participants following a linguistic example description, revealing two findings: eye movement “signatures” associated with distinct reference frames as expressed in language, and transfer of these eye movement patterns just prior to spatial description for different (later) picture descriptions. Both verbal description and visual cueing similarly influence language production choice through manipulation of visual attention, suggesting a unified theory of constraints affecting spatial language choice

Therapeutic options for chronic inflammatory demyelinating polyradiculoneuropathy: a systematic review

Background: Chronic inflammatory demyelinating polyradiculoneuropathy is a rare acquired immune-mediated progressive or relapsing disorder causing peripheral neuropathic disease of duration more than two months. Many individuals with chronic inflammatory demyelinating polyradiculoneuropathy fail to make a long-term recovery with current treatment regimes. The aim of this study was to prospectively review the literature to determine the effectiveness of therapies for chronic inflammatory demyelinating polyradiculoneuropathy. Methods: Articles published from January 1990 to December 2012 were searched for studies to treat adults with chronic inflammatory demyelinating polyradiculoneuropathy. Peer-reviewed full-text articles published in English were included. Results: Nine placebo-controlled double-blinded randomised trials were reviewed to treat subjects with chronic inflammatory demyelinating polyradiculoneuropathy exhibiting various degrees of effectiveness. The most effect treatments were; three randomised controlled trials using intravenous immunoglobulin, a study comparing pulsed dexamethasone and short term prednisolone and rituximab all showed promising results and were well tolerated. Conclusion: IVIg and corticosteroids remain first line treatments for CIDP. Therapies using monoclonal antibodies, such as Rituximab and Natalizumab offer the most promise for treatment of Chronic inflammatory demyelinating polyradiculoneuropathy however they also need further research, as does the use of stem cell therapy for treating Chronic inflammatory demyelinating polyradiculoneuropathy. Large randomised controlled trials and better patient selection are required to address responsiveness of CIDP patients to conventional treatments to elucidate mechanisms of action and future directions for therapeutic improvement.Richard J Bright, Jenny Wilkinson and Brendon J Coventr