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Selected Abstracts

Low-dose weekly platinum-based chemoradiation for advanced head and neck cancer,,

John M. Watkins MD
Abstract Objectives/Hypothesis: The optimal concurrent chemoradiotherapy regimen for definitive treatment of locoregionally advanced head and neck cancer remains to be determined. The present investigation reports toxicities, disease control, patterns of failure, and survival outcomes in a large mature cohort of patients treated with low-dose weekly platinum-based concurrent chemoradiotherapy. Study Design: Retrospective single-institution series. Methods: Toxicity and outcome data for locoregionally advanced head and neck cancer patients treated with low-dose weekly platinum-based chemotherapy concurrent with standard fractionation radiotherapy were retrospectively collected and analyzed from a clinical database. Survival analysis methods, including Kaplan-Meier estimation and competing risks analysis, were used to assess locoregional disease control, freedom from failure, and overall survival. Results: Ninety-six patients were eligible for the present analysis. Nearly all patients had American Joint Committee on Cancer clinical stage III to IVB disease (99%). Severe acute toxicities included grade 3 mucositis (61%), grade 3/4 nausea (27%/1%), and grade 3 neutropenia (8%). Thirty-seven patients (38%) required hospitalization for a median of 7 days (range, 1,121). Ninety-two percent of patients completed the fully prescribed course of radiotherapy, and 87% completed ,6 cycles of chemotherapy. At a median survivor follow-up of 40 months (range, 8,68), 47% of patients were without evidence of disease recurrence. The estimated 4-year freedom from failure and overall survival were 48% and 58%, respectively. Initial site(s) of disease failure were locoregional for 22 patients, locoregional and distant (five patients), and distant only (14 patients). Conclusions: Weekly low-dose platinum-based chemotherapy with full-dose daily radiotherapy is a tolerable alternative regimen for locoregionally advanced head and neck cancers, with comparable efficacy and patterns of failure to alternative regimens. Laryngoscope, 2010 [source]

Primary relapse of acute lymphoblastic leukemia in a cervical smear: A case report

Akiko Ikuta M.D.
Abstract Uterine cervix and corpus are rarely the initial site of relapse in leukemia or lymphoma. We report herein a case of uterine cervical relapse with B-cell acute lymphoblastic leukemia (ALL). The patient, a 60-yr-old woman, had a history of ALL that had been in remission for 2 yr after chemotherapy. She presented with a chief complaint of genital bleeding. In a routine cervico-vaginal Papanicolau smear, abundant atypical lymphoid cells with round-to-oval nuclei, scant cytoplasm, and high nuclear to cytoplasmic ratios was observed. The nuclei of these cells had fine and dark chromatin and thickened nuclear membranes, with one or several nucleoli being visible. Biopsy under colposcope was performed, and a diagnosis of relapse of ALL was confirmed. The ongoing genital bleeding presented a problem with clinical management of the patient. It was decided to proceed with hysterectomy to end that problem and thereafter proceed with therapy directed against the leukemia. Our results suggest that in patients with known extrauterine cancer, the presence of malignancy in uterine cellular samples provides information regarding the extent of the neoplasm. Diagn. Cytopathol. 2006;34:499,502. © 2006 Wiley-Liss, Inc. [source]

Caspr reveals an aggregation of nodes and flanking node free zones at the rat trigeminal sensory root and dorsal root entry zones

GLIA, Issue 3 2005
Michael A. Henry
Abstract The sensory root entry zone demarcates the transition from the peripheral nervous system (PNS) to the central nervous system (CNS). In this study, we describe the organization of nodes of Ranvier at the trigeminal sensory and dorsal root entry zones of the rat. Caspr immunoreactivity (IR) was used to identify the paranodal region of nodes of Ranvier, while L-MAG-IR was used to identify CNS oligodendrocytes. Immunofluorescence confocal microscopy revealed a dense aggregation of nodes precisely at the PNS to CNS transition with prominent node-depleted zones on either side, while L-MAG-IR was confined to ensheathing fibers on the central side of nodes located in this dense band and identified these as transitional nodes. Morphometric analysis of the PNS and CNS sides of the trigeminal and the PNS side of the dorsal root entry zones confirmed the presence of virtually node-free domains flanking the transitional zone. Further, the reappearance of nodes on the far side of the node-free zones strongly correlated with nodal diameter, with small nodes reappearing first. These findings suggest that the PNS/CNS transition may represent the initial site of myelination of the primary afferent axon within this area. © 2004 Wiley-Liss, Inc. [source]

Morphogenetic significance of the conchal furrow in nautiloids: evidence from early embryonic shell development of Jurassic Nautilida

LETHAIA, Issue 3 2003
As reported by many workers over the past two centuries, the inner part of the shell of various straight and coiled Palaeozoic to tertiary nautiloid taxa bears a continuous mid-ventral furrow that extends into the phragmocone and the body chamber nearly to the aperture. Study of the early embryonic shell development of Jurassic Nautilida shows that the most apical part of this so-called conchal furrow originates from the inner part of the initial, calcified shell apex, in line with the inner ventral termination of the central linear depression of the cicatrix, the initial site of shell deposition. The conchal furrow corresponds to a morphological feature arising as a developmental by-product. Rare specimens of scattered ammonoid species (and possibly of bactritoids) display a similar feature, whereas their protoconch lacks a cicatrix. However, the protoconch of recent cuttlefish, Sepia officinalis, often displays a longitudinal fold of the primary shell epithelium. A longitudinal groove or a pair of grooves appears connected with this cicatrix-like structure. Although the mid-ventral ridge in ammonoids must probably be viewed as an incidental ,fabricational noise', whether or not it originates from a so far undocumented optional ridge on the protoconch or from some other structure related to shell development remains an open question. [source]

Limits on the location of planetesimal formation in self-gravitating protostellar discs

C. J. Clarke
ABSTRACT In this Letter, we show that if planetesimals form in spiral features in self-gravitating discs, as previously suggested by the idealized simulations of Rice et al., then in realistic protostellar discs, this process will be restricted to the outer regions of the disc (i.e. at radii in excess of several tens of au). This restriction relates to the requirement that dust has to be concentrated in spiral features on a time-scale that is less than the (roughly dynamical) lifetime of such features, and that such rapid accumulation requires spiral features whose fractional amplitude is not much less than unity. This in turn requires that the cooling time-scale of the gas is relatively short, which restricts the process to the outer disc. We point out that the efficient conversion of a large fraction of the primordial dust in the disc into planetesimals could rescue this material from the well-known problem of rapid inward migration at an approximate metre-size scale and that in principle the collisional evolution of these objects could help to resupply small dust to the protostellar disc. We also point out the possible implications of this scenario for the location of planetesimal belts inferred in debris discs around main sequence stars, but stress that further dynamical studies are required in order to establish whether the disc retains a memory of the initial site of planetesimal creation. [source]

Does Alzheimer's disease begin in the brainstem?

G. Simic
Although substantial evidence indicates that the progression of pathological changes of the neuronal cytoskeleton is crucial in determining the severity of dementia in Alzheimer's disease (AD), the exact causes and evolution of these changes, the initial site at which they begin, and the neuronal susceptibility levels for their development are poorly understood. The current clinical criteria for diagnosis of AD are focused mostly on cognitive deficits produced by dysfunction of hippocampal and high-order neocortical areas, whereas noncognitive, behavioural and psychological symptoms of dementia such as disturbances in mood, emotion, appetite, and wake,sleep cycle, confusion, agitation and depression have been less considered. The early occurrence of these symptoms suggests brainstem involvement, and more specifically of the serotonergic nuclei. In spite of the fact that the Braak and Braak staging system and National Institutes of Aging , Reagan Institute (NIA-RI) criteria do not include their evaluation, several recent reports drew attention to the possibility of selective and early involvement of raphe nuclei, particularly the dorsal raphe nucleus (DRN), in the pathogenesis of AD. Based on these findings of differential susceptibility and anatomical connectivity, a novel pathogenetic scheme of AD progression was proposed. Although the precise mechanisms of neurofibrillary degeneration still await elucidation, we speculated that cumulative oxidative damage may be the main cause of DRN alterations, as the age is the main risk factor for sporadic AD. Within such a framework, ,-amyloid production is considered only as one of the factors (although a significant one in familial cases) that promotes molecular series of events underlying AD-related neuropathological changes. [source]

Analysis of gene expression in human bronchial epithelial cells upon influenza virus infection and regulation by p38 mitogen-activated protein kinase and c-Jun-N-terminal kinase

RESPIROLOGY, Issue 2 2008
Shinichi HAYASHI
Background and objective: Airway epithelial cells, which are the initial site of influenza virus (IV) infection, participate in the inflammatory process through the expression of various genes. In this process, mitogen-activated protein kinase (MAPK) may be associated with the expression of many genes, but its precise role remains unknown. Methods: A comprehensive analysis was performed of gene expression in human bronchial epithelial cells upon IV infection, using an Affymetrix gene chip containing 12 000 genes. Regulation of gene expression by MAPK was also analysed. Results: A total of 5998 genes were detected. Upon IV infection, 165 genes were upregulated and 49 of these were interferon-stimulated genes. The functions of 129 genes, including 14 apoptosis-related genes and 6 antiviral genes, were well characterized; however, those of 36 genes were unknown. The expression of 29 genes was inhibited either by SB 203580, a specific inhibitor of p38 MAPK, or by CEP-11004, a specific inhibitor of the c-Jun-N-terminal kinase (JNK) cascade, and the percentage inhibition by SB 203580 correlated with that by CEP-11004, suggesting that p38 and JNK participate in a common downstream pathway involved in the regulation of gene expression. p38 MAPK- or JNK-dependent genes were functionally classified into diverse categories. Conclusions: Although further studies are needed to obtain a more complete understanding of gene expression and the role of MAPK in gene expression, the present results are important in understanding the molecular mechanisms involved in the response of bronchial epithelial cells to IV infection. [source]

High incidence of disease recurrence in the brain and leptomeninges in patients with nonsmall cell lung carcinoma after response to gefitinib

CANCER, Issue 11 2005
Antonio M. P. Omuro M.D.
Abstract BACKGROUND Gefitinib is an epidermal growth factor receptor tyrosine kinase inhibitor that induces an early and dramatic response in 10% of patients with advanced nonsmall cell lung carcinoma (NSCLC). Long- term outcome and patterns of disease recurrence after response have not been described. METHODS The authors evaluated 139 patients with NSCLC treated with gefitinib at Memorial Sloan-Kettering Cancer Center (New York, NY) between 1998 and 2002. They focused on patterns of disease recurrence, risk of brain metastases (BM) and leptomeningeal metastasis (LM), and long-term outcome after initial response to gefitinib. RESULTS Of the 139 patients treated with gefitinib, 21 (15%) achieved a partial response. The median age of the responders was 64 years (range, 38,87 years), the median Karnofsky performance score was 80 (range, 60,90), and 4 of the patients were men. All responders had adenocarcinoma. The central nervous system (CNS) was the initial site of disease recurrence in 7 (33%) patients (BM in 5 and LM in 2). In 9 (43%) patients, the initial site of disease recurrence was the lung and in 1 it was the liver and bone. Four (57%) of the patients with disease recurrence in the CNS had lung disease under control. BM also developed in 2 patients who had initial disease recurrence in the lungs. The actuarial 5-year incidence of CNS metastases was 60%. The median overall survival periods were 15 months and 23 months for patients with and without CNS metastases, respectively (P = 0.24). CONCLUSIONS The CNS was a frequent site of disease recurrence in patients with NSCLC after an initial response to gefitinib, regardless of disease control in the lungs. Patients should be carefully monitored for neurologic symptoms. Intrinsic resistance of metastatic clones, incomplete CNS penetrance of the drug, and longer survival are possible explanations for this high incidence. Cancer 2005. © 2005 American Cancer Society. [source]