Outcome of ATP-based tumor chemosensitivity assay directed chemotherapy in heavily pre-treated recurrent ovarian carcinoma

BACKGROUND: We wished to evaluate the clinical response following ATP-Tumor Chemosensitivity Assay (ATP-TCA) directed salvage chemotherapy in a series of UK patients with advanced ovarian cancer. The results are compared with that of a similar assay used in a different country in terms of evaluability and clinical endpoints. METHODS: From November 1998 to November 2001, 46 patients with pre-treated, advanced ovarian cancer were given a total of 56 courses of chemotherapy based on in-vitro ATP-TCA responses obtained from fresh tumor samples or ascites. Forty-four patients were evaluable for results. Of these, 18 patients had clinically platinum resistant disease (relapse < 6 months after first course of chemotherapy). There was evidence of cisplatin resistance in 31 patients from their first ATP-TCA. Response to treatment was assessed by radiology, clinical assessment and tumor marker level (CA 125). RESULTS: The overall response rate was 59% (33/56) per course of chemotherapy, including 12 complete responses, 21 partial responses, 6 with stable disease, and 15 with progressive disease. Two patients were not evaluable for response having received just one cycle of chemotherapy: if these were excluded the response rate is 61%. Fifteen patients are still alive. Median progression free survival (PFS) was 6.6 months per course of chemotherapy; median overall survival (OAS) for each patient following the start of TCA-directed therapy was 10.4 months (95% confidence interval 7.9-12.8 months). CONCLUSION: The results show similar response rates to previous studies using ATP-TCA directed therapy in recurrent ovarian cancer. The assay shows high evaluability and this study adds weight to the reproducibility of results from different centre

The blurring boundaries between synchronicity and asynchronicity:new communicative situations in work-related Instant Messaging

Instant messaging is one of the most popular communication technologies in virtual teams, enabling interactions to intertwine whole working days, thus creating the sense of copresence for team members who are geographically dispersed. Through close linguistic analyses of naturally occurring data from a virtual team, this article discusses the implications of two novel communicative situations enabled by instant messaging: presence information and the persistence of transcript. The preliminary findings of this study indicate that these new communicative situations require the flouting or rethinking of previously existing interactional norms and that communicative practices employed by the team members are not yet conventionalized/normalized, the expectations and interpretations of interactional rituals and timing vary highly, even within the same virtual team

Linear stability analysis of retrieval state in associative memory neural networks of spiking neurons

We study associative memory neural networks of the Hodgkin-Huxley type of spiking neurons in which multiple periodic spatio-temporal patterns of spike timing are memorized as limit-cycle-type attractors. In encoding the spatio-temporal patterns, we assume the spike-timing-dependent synaptic plasticity with the asymmetric time window. Analysis for periodic solution of retrieval state reveals that if the area of the negative part of the time window is equivalent to the positive part, then crosstalk among encoded patterns vanishes. Phase transition due to the loss of the stability of periodic solution is observed when we assume fast alpha-function for direct interaction among neurons. In order to evaluate the critical point of this phase transition, we employ Floquet theory in which the stability problem of the infinite number of spiking neurons interacting with alpha-function is reduced into the eigenvalue problem with the finite size of matrix. Numerical integration of the single-body dynamics yields the explicit value of the matrix, which enables us to determine the critical point of the phase transition with a high degree of precision.Comment: Accepted for publication in Phys. Rev.

Are Three Additional Cycles of Chemotherapy Useful in Patients with Advanced-stage Epithelial Ovarian Cancer After a Complete Response to Six Cycles of Intravenous Adjuvant Paclitaxel and Carboplatin?†

BACKGROUND: To evaluate the efficacy of three additional cycles of chemotherapy in patients with the International Federation of Gynecology and Obstetrics Stage III or IV, who achieved a complete response after six cycles of intravenous adjuvant paclitaxel/carboplatin after surgery. METHODS: The clinical data of 94 patients with complete response after six cycles of adjuvant paclitaxel/carboplatin after surgery between January 1997 and March 2007 were reviewed retrospectively. Three additional cycles using the same chemotherapy were administered to 57 patients as consolidation chemotherapy (Group 1). Thirty-seven patients without the additional cycles served as controls (Group 2). Disease-free survival (DFS) and overall survival (OS) were evaluated using the Kaplan-Meier method with the log-rank test. The importance of consolidation chemotherapy as a prognostic factor affecting survival was examined using the Cox's proportional hazard analysis. The incidence of chemotherapy-induced hematological toxicities was compared between the two groups using chi-square test. RESULTS: Median DFS and mean OS were not significantly different between the two groups (15 versus 22 months, P = 0.703; 69 versus 73 months, P = 0.891, respectively). Consolidation chemotherapy was not a prognostic factor of survival although optimal debulking surgery and lower value of serum CA-125 levels after six cycles of the chemotherapy were prognostic factors improving DFS (P < 0.01). Grade 3 or 4 leukopenia was more common in patients treated with consolidation chemotherapy than in those not treated (50.9 versus 21.6%, P = 0.004). CONCLUSION: Consolidation chemotherapy using paclitaxel/carboplatin may be inefficient and relatively toxic to advanced-stage epithelial ovarian cancer patients with complete response to six cycles of the same chemotherapy after surgery

Weekly platinum chemotherapy for recurrent ovarian cancer

British Journal of Cancer (2002) 86, 2–4. DOI: 10.1038/sj/bjc/6600062 www.bjcancer.co

Fatal outcome of a hypersensitivity reaction to paclitaxel: a critical review of premedication regimens

Hypersensitivity reactions (HSRs) to paclitaxel are frequently encountered in patients receiving this antitumour drug. Administration of histamine H1- and H2-receptor antagonists and corticosteroids has been shown to reduce significantly the risk of developing an HSR in patients receiving taxanes. In this case report, we describe the fatal outcome of an HSR in a patient receiving paclitaxel despite short-course premedication. The level of evidence supporting the short-course i.v. premedication schedule is challenged, as it is not compatible with the pharmacokinetic properties of dexamethasone

Dualities in integrable systems and N=2 theories

We discuss dualities of the integrable dynamics behind the exact solution to the N=2 SUSY YM theory. It is shown that T duality in the string theory is related to the separation of variables procedure in dynamical system. We argue that there are analogues of S duality as well as 3d mirror symmetry in the many-body systems of Hitchin type governing low-energy effective actions.Comment: 16 pages, Latex, Talk given at QFTHEP-99, Moscow, May 27-June

Varicella-Zoster viruses associated with post-herpetic neuralgia induce sodium current density increases in the ND7-23 Nav-1.8 neuroblastoma cell line

Post-herpetic neuralgia (PHN) is the most significant complication of herpes zoster caused by reactivation of latent Varicella-Zoster virus (VZV). We undertook a heterologous infection in vitro study to determine whether PHN-associated VZV isolates induce changes in sodium ion channel currents known to be associated with neuropathic pain. Twenty VZV isolates were studied blind from 11 PHN and 9 non-PHN subjects. Viruses were propagated in the MeWo cell line from which cell-free virus was harvested and applied to the ND7/23-Nav1.8 rat DRG x mouse neuroblastoma hybrid cell line which showed constitutive expression of the exogenous Nav 1.8, and endogenous expression of Nav 1.6 and Nav 1.7 genes all encoding sodium ion channels the dysregulation of which is associated with a range of neuropathic pain syndromes. After 72 hrs all three classes of VZV gene transcripts were detected in the absence of infectious virus. Single cell sodium ion channel recording was performed after 72 hr by voltage-clamping. PHN-associated VZV significantly increased sodium current amplitude in the cell line when compared with non-PHN VZV, wild-type (Dumas) or vaccine VZV strains ((POka, Merck and GSK). These sodium current increases were unaffected by acyclovir pre-treatment but were abolished by exposure to Tetrodotoxin (TTX) which blocks the TTX-sensitive fast Nav 1.6 and Nav 1.7 channels but not the TTX-resistant slow Nav 1.8 channel. PHN-associated VZV sodium current increases were therefore mediated in part by the Nav 1.6 and Nav 1.7 sodium ion channels. An additional observation was a modest increase in message levels of both Nav1.6 and Nav1.7 mRNA but not Nav 1.8 in PHN virally infected cells