bluuebunny/crossref_metadata_2025 huggingface dataset:
MAP kinase pathways and calcitonin influence CD44 alternate isoform expression in prostate cancer cells
Authors: Robbins Eric W , Travanty Emily A , Yang Kui , Iczkowski Kenneth A
Published: September 2008

Background

Dysregulated expression and splicing of cell adhesion marker CD44 is found in many types of cancer. In prostate cancer (PC) specifically, the standard isoform (CD44s) has been found to be downregulated compared with benign tissue whereas predominant variant isoform CD44v7-10 is upregulated. Mitogen-activated protein kinase pathways and paracrine calcitonin are two common factors linked to dysregulated expression and splicing of CD44 in cancer. Calcitonin has been found to increase proliferation and invasion in PC acting through the protein kinase A pathway.

Methods

In androgen-independent PC with known high CD44v7-10 expression, CD44 total and CD44v7-10 RNA or protein were assessed in response to exogenous and endogenous calcitonin and to inhibitors of protein kinase A, MEK, JNK, or p38 kinase. Benign cells and calcitonin receptor-negative PC cells were also tested.

Results

MEK or p38 but not JNK reduced CD44 total RNA by 40%–65% in cancer and benign cells. Inhibition of protein kinase A reduced CD44 total and v7-10 protein expression. In calcitonin receptor-positive cells only, calcitonin increased CD44 variant RNA and protein by 3 h and persisting to 48 h, apparently dependent on an uninhibited p38 pathway. Cells with constitutive CT expression showed an increase in CD44v7-10 mRNA but a decrease in CD44 total RNA.

Conclusion

The MEK pathway increases CD44 RNA, while calcitonin, acting through the protein kinase A and p38 pathway, facilitates variant splicing. These findings could be used in the formulation of therapeutic methods for PC targeting CD44 alternate splicing.
Loss of heterozygosity at the ATBF1-A locus located in the 16q22 minimal region in breast cancer
Authors: Kai Kazuharu , Zhang Zhenhuan , Yamashita Hiroko , Yamamoto Yutaka , Miura Yutaka , Iwase Hirotaka
Published: September 2008

Background

Loss of heterozygosity (LOH) on the long arm of chromosome 16 is one of the most frequent genetic events in solid tumors. Recently, theAT-motif binding factor 1(ATBF1)-Agene, which has been assigned to chromosome 16q22.3-23.1, was identified as a plausible candidate for tumor suppression in solid tumors due to its functional inhibition of cell proliferation and high mutation rate in prostate cancer. We previously reported that a reduction inATBF1-AmRNA levels correlated with a worse prognosis in breast cancer. However, the mechanisms regulating the reduction ofATBF1-AmRNA levels (such as mutation, methylation in the promoter region, or deletion spanning the coding region) have not been fully examined. In addition, few studies have analyzed LOH status at theATBF1-Alocus, located in the 16q22 minimal region.

Methods

Profiles ofATBF1-AmRNA levels that we previously reported for 127 cases were used. In this study, breast cancer specimens as well as autologous blood samples were screened for LOH using 6 polymorphic microsatellite markers spanning chromosome band 16q22. For mutational analysis, we selected 12 cases and analyzed selected spots in theATBF1-Acoding region at which mutations have been frequently reported in prostate cancer.

Results

Forty-three cases that yielded clear profiles of LOH status at both D16S3106 and D16S3018 microsatellites, nearest to the location of theATBF1-Agene, were regarded as informative and were classified into two groups: LOH (22 cases) and retention of heterozygosity (21 cases). Comparative assessment of theATBF1-AmRNA levels according to LOH status at theATBF1-Alocus demonstrated no relationship between them. In the 12 cases screened for mutational analysis, there were no somatic mutations with amino acid substitution or frameshift; however, two germ line alterations with possible polymorphisms were observed.

Conclusion

These findings imply thatATBF1-AmRNA levels are regulated at the transcriptional stage, but not by genetic mechanisms, deletions (LOH), or mutations.
Smoking, health and ageing
Authors: Nicita-Mauro Vittorio , Basile Giorgio , Maltese Giuseppe , Nicita-Mauro Claudio , Gangemi Sebastiano , Caruso Calogero
Published: September 2008

On March 19, 2008 a Symposium on Pathophysiology of Ageing and Age-Related diseases was held in Palermo, Italy. Here, the lecture of V. Nicita-Mauro on Smoking, health and ageing is summarized. Smoking represents an important ageing accelerator, both directly by triggering ana inflammatory responses, and indirectly by favoring the occurrence of several diseases where smoking is a recognized risk factor. Hence, non-smokers can delay the appearance of diseases and of ageing process, so attaining longevity.
Descending Serotonergic Controls Regulate Inflammation-Induced Mechanical Sensitivity and Methyl-CpG-Binding Protein 2 Phosphorylation in the Rat Superficial Dorsal Horn
Authors: Géranton Sandrine M , Fratto Vincenza , Tochiki Keri K , Hunt Stephen P
Published: September 2008

Background:

Regulation of pain states is, in part, dependent upon plastic changes in neurones within the superficial dorsal horn. There is also compelling evidence that pain states are under the control of descending projections from the brainstem. While a number of transcription factors including Methyl-CpG-binding protein 2 (MeCP2), Zif268 and Fos have been implicated in the regulation of dorsal horn neurone sensitization following injury, modulation of their activity by descending controls has not been investigated.

Results:

Here, we describe how descending controls regulate MeCP2 phosphorylation (P-MeCP2), known to relieve transcriptional repression by MeCP2, and Zif268 and Fos expression in the rat superficial dorsal horn, after CFA injection into the hind paw. First, we report that CFA significantly increased P-MeCP2 in Lamina I and II, from 30 min post injection, with a maximum reached after 1 h. The increase in P-MeCP2 paralleled that of Zif268 and Fos, and P-MeCP2 was expressed in large sub-populations of Zif268 and Fos expressing neurones. Serotonergic depletion of the lumbar spinal cord with 5,7 di-hydroxytryptamine creatinine sulphate (5,7-DHT) reduced the inflammation evoked P-MeCP2 in the superficial dorsal horn by 57%, and that of Zif268 and Fos by 37.5% and 30% respectively. Although 5,7-DHT did not change primary thermal hyperalgesia, it significantly attenuated mechanical sensitivity seen in the first 24 h after CFA.

Conclusion:

We conclude that descending serotonergic pathways play a crucial role in regulating gene expression in the dorsal horn and mechanical sensitivity associated with an inflammatory pain state.
The impact of functional imaging on radiation medicine
Authors: Sharma Nidhi , Neumann Donald , Macklis Roger
Published: September 2008

Radiation medicine has previously utilized planning methods based primarily on anatomic and volumetric imaging technologies such as CT (Computerized Tomography), ultrasound, and MRI (Magnetic Resonance Imaging). In recent years, it has become apparent that a new dimension of non-invasive imaging studies may hold great promise for expanding the utility and effectiveness of the treatment planning process. Functional imaging such as PET (Positron Emission Tomography) studies and other nuclear medicine based assays are beginning to occupy a larger place in the oncology imaging world. Unlike the previously mentioned anatomic imaging methodologies, functional imaging allows differentiation between metabolically dead and dying cells and those which are actively metabolizing. The ability of functional imaging to reproducibly select viable and active cell populations in a non-invasive manner is now undergoing validation for many types of tumor cells. Many histologic subtypes appear amenable to this approach, with impressive sensitivity and selectivity reported.

For clinical radiation medicine, the ability to differentiate between different levels and types of metabolic activity allows the possibility of risk based focal treatments in which the radiation doses and fields are more tightly connected to the perceived risk of recurrence or progression at each location.

This review will summarize many of the basic principles involved in the field of functional PET imaging for radiation oncology planning and describe some of the major relevant published data behind this expanding trend.
Incidence of hip replacement among national health insurance enrollees in Taiwan
Authors: Lai Yu-Shu , Wei Hung-Wen , Cheng Cheng-Kung
Published: September 2008

Background

There is no national joint replacement registry in the country of Asia and reports of national outcomes of joint replacement in Asia as yet. Therefore, this study was then to report a national data of the number of hip replacements, incidence rate, demographic characteristics of hip replacement patients, and short-time survival rate after hip replacement of Han Chinese in Taiwan.

Methods

We analyzed 105,688 cases of hip replacements (including primary partial hip replacement, primary total hip replacement and revision of hip replacement) from National Health Insurance research database between 1996 and 2004. The survival rate of primary hip replacement was estimated for each disease by the Kaplan-Meier method.

Results

Average annual number of primary partial hip replacement and primary total hip replacement were 4,257 and 6,206 cases, respectively. The most two common diagnosis of primary partial hip replacement were femoral neck fractures (73.6%, 34% men, mean age 76 years) and avascular necrosis (18.0%, 84% men, mean age 48 years). In primary total hip replacements, the most two common diagnosis were avascular necrosis (46.9%, 79% men, mean age 50 years) and osteoarthrosis (41.6%, 43% men, mean age 60 years). Both the number of primary partial hip replacements and primary total hip replacements increased steadily between 1996 and 2004. The cumulative survival of primary partial hip replacements and primary total hip replacements in all patients were 93.97% and 79.47% in 9 years follow-up, respectively.

Conclusion

Avascular necrosis is the main disease in total hip replacement in Taiwan. The epidemiology of hip diseases was different between Han Chinese (in Taiwan) and Caucasian and the number of hip replacements increased substantially in Taiwan between 1996 and 2004.
Foot and ankle surgery in Australia: a descriptive analysis of the Medicare Benefits Schedule database, 1997–2006
Authors: Menz Hylton B , Gilheany Mark F , Landorf Karl B
Published: September 2008

Background

Foot and ankle problems are highly prevalent in the general community and a substantial proportion of people seek surgical treatment to alleviate foot pain and deformity. However, the epidemiology of foot and ankle surgery has not been examined in detail. Therefore, the aim of this study was to examine patterns and costs of private sector foot surgery provision in Australia.

Methods

Data pertaining to all foot and ankle surgical procedures for the calendar years 1997–2006 were extracted from the Australian Medicare Benefits Schedule (MBS) database and were cross‐tabulated by sex and age. Descriptive analyses were undertaken to assess sex and age differences in the number and type of procedures performed and to assess for temporal trends over the ten year assessment period. The total cost to Medicare of subsiding surgeons’ fees in 2006 was also determined.

Results

During the 1997–2006 period, 996,477 surgical procedures were performed on the foot and ankle by private surgeons in Australia. Approximately equal numbers of procedures were performed on males (52%) and females (48%). However, males were more likely to undergo toenail, ankle, clubfoot, tarsal coalition and congenital vertical talus surgery, whereas females were more likely to undergo lesser toe, first metatarsophalangeal joint (MPJ), neuroma, heel, rearfoot and lesser MPJ surgery. The total number of procedures was stable over the assessment period, however there was a relative increase in the number of procedures performed on people aged over 55 years. The total contribution of Medicare to subsiding surgeons’ fees for procedures performed in 2006 was $14 M.

Conclusion

Foot and ankle surgery accounts for a considerable degree of healthcare expenditure in Australia, and the number of procedures in those aged over 55 years is increasing. Given the ageing demographics of the Australian population, the future public health and economic impact of foot morbidity is likely to be substantial. Strategies need to be implemented to ensure that the surgical labour force is adequate to address this increasing demand.
ERalpha-status of disseminated tumour cells in bone marrow of primary breast cancer patients
Authors: Fehm Tanja , Krawczyk Natalia , Solomayer Erich-Franz , Becker-Pergola Graziella , Dürr-Störzer Silke , Neubauer Hans , Seeger Harald , Staebler Annette , Wallwiener Diethelm , Becker Sven
Published: September 2008

Introduction

Isolated disseminated tumour cells (DTC) are regarded as surrogate markers for minimal residual disease in breast cancer. Characterisation of these cells could help understand the known limitations of adjuvant therapy. Of particular interest is their oestrogen-receptor (ER) status because endocrine adjuvant therapy remains a cornerstone of breast cancer treatment.

Methods

Bone marrow (BM) aspirates from 254 patients with primary breast cancer were included in this study. A double immunofluorescence staining procedure was established for the identification of cytokeratin (CK) positive/Erα-positive cells. ERα status of the primary tumour was assessed immunohistochemically using the same antibody against ERα.

Results

In 107 of 254 (42%) breast cancer patients, CK-positive cells could be detected in the BM. More than one DTC in the BM was observed in 38 of the 107 patients. The number of detected cells ranged between 1 and 55 cells per 2 × 106 mononuclear cells. DTCs demonstrated ERα positivity in 12% of the patients. The ERα expression was heterogeneous in 10 of the 38 (26%) patients with more than one DTC. The concordance rate of ERα status between primary tumour and DTC was 28%. Only 12 of 88 patients with ERα-positive tumours also had ERα-positive DTCs.

Conclusions

Primary tumours and DTCs displayed a concordant ERα status in only 28% of cases. Most of the DTCs were ERα negative despite the presence of an ERα-positive primary tumour. These findings further underline the distinct nature of DTCs and may explain the failure rates seen in conventional endocrine adjuvant therapy.
Clinical feasibility of (neo)adjuvant taxane-based chemotherapy in older patients: analysis of >4,500 patients from four German randomized breast cancer trials
Authors: Loibl Sibylle , von Minckwitz Gunter , Harbeck Nadia , Janni Wolfgang , Elling Dirk , Kaufmann Manfred , Eggemann Holm , Nekljudova Valentina , Sommer Harald , Kiechle Marion , Kümmel Sherko
Published: September 2008

Introduction

Despite the fact that people older than 65 years of age have the highest incidence of developing breast cancer, these patients are excluded from clinical trials in most cases. Furthermore, most physicians tend towards therapy regimens without the use of dose-dense, highly active taxane-based treatments because of a lack of data regarding toxicities of these compounds in older patients.

Methods

Pooled side-effect data were analyzed from four prospective, randomized clinical trials in which patients of different age groups (< 60 years, between 60 and 64 years, and > 64 years) with primary breast cancer received taxane-based chemotherapy.

Results

Dose delays, dose reductions, hospitalization, and therapy discontinuation increased with age. Hematologic toxicities and some nonhematologic toxicities were generally more common in older patients. Leucopenia increased from 55.3% in patients aged < 60 years to 65.5% in patients aged > 64 years (P < 0.001), and neutropenia increased from 46.9% to 57.4% (P < 0.001). There was no difference, however, in clinically more relevant febrile neutropenia between the different age groups. Thrombopenia shows a similar age-dependent increase, whereas there is no difference between the age groups concerning anemia. Hot flushes and elevated liver enzymes decreased with increasing age.

Conclusions

The present pooled analysis of a substantial cohort of older primary breast cancer patients demonstrates that taxane-containing (neo)adjuvant chemotherapy is feasible in older patients and that toxicity can be reduced by sequential therapy regimens.
Entropy and bispectral index for assessment of sedation, analgesia and the effects of unpleasant stimuli in critically ill patients: an observational study
Authors: Haenggi Matthias , Ypparila-Wolters Heidi , Bieri Christine , Steiner Carola , Takala Jukka , Korhonen Ilkka , Jakob Stephan M
Published: September 2008

Introduction

Sedative and analgesic drugs are frequently used in critically ill patients. Their overuse may prolong mechanical ventilation and length of stay in the intensive care unit. Guidelines recommend use of sedation protocols that include sedation scores and trials of sedation cessation to minimize drug use. We evaluated processed electroencephalography (response and state entropy and bispectral index) as an adjunct to monitoring effects of commonly used sedative and analgesic drugs and intratracheal suctioning.

Methods

Electrodes for monitoring bispectral index and entropy were placed on the foreheads of 44 critically ill patients requiring mechanical ventilation and who previously had no brain dysfunction. Sedation was targeted individually using the Ramsay Sedation Scale, recorded every 2 hours or more frequently. Use of and indications for sedative and analgesic drugs and intratracheal suctioning were recorded manually and using a camera. At the end of the study, processed electroencephalographical and haemodynamic variables collected before and after each drug application and tracheal suctioning were analyzed. Ramsay score was used for comparison with processed electroencephalography when assessed within 15 minutes of an intervention.

Results

The indications for boli of sedative drugs exhibited statistically significant, albeit clinically irrelevant, differences in terms of their association with processed electroencephalographical parameters. Electroencephalographical variables decreased significantly after bolus, but a specific pattern in electroencephalographical variables before drug administration was not identified. The same was true for opiate administration. At both 30 minutes and 2 minutes before intratracheal suctioning, there was no difference in electroencephalographical or clinical signs in patients who had or had not received drugs 10 minutes before suctioning. Among patients who received drugs, electroencephalographical parameters returned to baseline more rapidly. In those cases in which Ramsay score was assessed before the event, processed electroencephalography exhibited high variation.

Conclusions

Unpleasant or painful stimuli and sedative and analgesic drugs are associated with significant changes in processed electroencephalographical parameters. However, clinical indications for drug administration were not reflected by these electroencephalographical parameters, and barely by sedation level before drug administration or tracheal suction. This precludes incorporation of entropy and bispectral index as target variables for sedation and analgesia protocols in critically ill patients.
Polysomy 17 in Breast Cancer: Clinicopathologic Significance and Impact on HER-2 Testing
Authors: Vanden Bempt Isabelle , Van Loo Peter , Drijkoningen Maria , Neven Patrick , Smeets Ann , Christiaens Marie-Rose , Paridaens Robert , De Wolf-Peeters Christiane
Published: September 2008

Purpose

Polysomy 17 is frequently found in breast cancer and may complicate the interpretation of HER-2 testing results. We investigated the impact of polysomy 17 on HER-2 testing and studied its clinicopathologic significance in relation to HER2 gene amplification.

Patients and Methods

In 226 patients with primary invasive breast carcinoma, HER2 gene and chromosome 17 copy numbers were determined by dual-color fluorescent in situ hybridization (FISH). The interpretation of FISH results was based on either absolute HER2 gene copy number or the ratio HER2/chromosome 17. Results were correlated with HER-2 protein expression on immunohistochemistry (IHC), HER2 mRNA expression by reverse transcriptase polymerase chain reaction (RT-PCR), and with various clinicopathologic parameters.

Results

All cases with an equivocal HER-2 result by FISH, either by absolute HER2 copy number (44 of 226 patients; 19.5%) or by the ratio HER2/chromosome 17 (three of 226 patients; 1.3%), displayed polysomy 17. On its own, polysomy 17 was not associated with HER-2 overexpression on IHC or increased HER2 mRNA levels by RT-PCR. Moreover, and in contrast with HER2 gene amplification, polysomy 17 was not associated with high tumor grade, hormone receptor negativity, or reduced disease-free survival.

Conclusion

Polysomy 17 affects HER-2 testing in breast cancer and is a major cause of equivocal results by FISH. We show that tumors displaying polysomy 17 in the absence of HER2 gene amplification resemble more HER-2–negative than HER-2–positive tumors. These findings highlight the need for clinical trials to investigative whether polysomy 17 tumors benefit from HER-2–targeted therapy.
Phase III Study Comparing Exemestane With Tamoxifen As First-Line Hormonal Treatment of Metastatic Breast Cancer in Postmenopausal Women: The European Organisation for Research and Treatment of Cancer Breast Cancer Cooperative Group
Authors: Paridaens Robert J. , Dirix Luc Y. , Beex Louk V. , Nooij Marianne , Cameron David A. , Cufer Tanja , Piccart Martine J. , Bogaerts Jan , Therasse Patrick
Published: September 2008

Purpose

This phase III randomized open-label clinical trial was designed to evaluate the efficacy and safety of the steroidal aromatase inactivator exemestane versus the antiestrogen tamoxifen as first-line treatment for metastatic breast cancer (MBC) in postmenopausal women.

Patients and Methods

The study was conducted at 81 centers and enrolled postmenopausal patients with measurable hormone-sensitive metastatic or locally advanced breast cancer. Prior adjuvant chemotherapy and/or tamoxifen were allowed. One previous chemotherapy regimen and no prior hormone therapy for advanced disease were permitted. Patients were randomly assigned to receive exemestane 25 mg or tamoxifen 20 mg orally once daily until disease progression or unacceptable toxicity occurred.

Results

A total of 371 patients enrolled at 79 sites (182 exemestane, 189 tamoxifen) were included in the analysis. Both treatments were generally well tolerated without major toxicity. Overall response rate was greater for exemestane than for tamoxifen treatment (46% v 31%; odds ratio = 1.85; 95% CI, 1.21 to 2.82; P = .005). Median progression-free survival (PFS) was longer with exemestane (9.9 months; 95% CI, 8.7 to 11.8 months) than with tamoxifen (5.8 months; 95% CI, 5.3 to 8.1 months). However, these early differences (Wilcoxon P = .028) did not translate to a longer-term benefit in PFS, the primary study end point (log-rank P = .121). There was also no difference in survival between both study arms.

Conclusion

Exemestane is an effective and well-tolerated first-line hormonal treatment for postmenopausal women with MBC and offers significant early improvement in time to tumor progression when compared with tamoxifen.
Occurrence of Autoantibodies to Annexin I, 14-3-3 Theta and LAMR1 in Prediagnostic Lung Cancer Sera
Authors: Qiu Ji , Choi Gina , Li Lin , Wang Hong , Pitteri Sharon J. , Pereira-Faca Sandra R. , Krasnoselsky Alexei L. , Randolph Timothy W. , Omenn Gilbert S. , Edelstein Cim , Barnett Matt J. , Thornquist Mark D. , Goodman Gary E. , Brenner Dean E. , Feng Ziding , Hanash Samir M.
Published: September 2008

Purpose

We have implemented a high throughput platform for quantitative analysis of serum autoantibodies, which we have applied to lung cancer for discovery of novel antigens and for validation in prediagnostic sera of autoantibodies to antigens previously defined based on analysis of sera collected at the time of diagnosis.

Materials and Methods

Proteins from human lung adenocarcinoma cell line A549 lysates were subjected to extensive fractionation. The resulting 1,824 fractions were spotted in duplicate on nitrocellulose-coated slides. The microarrays produced were used in a blinded validation study to determine whether annexin I, PGP9.5, and 14-3-3 theta antigens previously found to be targets of autoantibodies in newly diagnosed patients with lung cancer are associated with autoantibodies in sera collected at the presymptomatic stage and to determine whether additional antigens may be identified in prediagnostic sera. Individual sera collected from 85 patients within 1 year before a diagnosis of lung cancer and 85 matched controls from the Carotene and Retinol Efficacy Trial (CARET) cohort were hybridized to individual microarrays.

Results

We present evidence for the occurrence in lung cancer sera of autoantibodies to annexin I, 14-3-3 theta, and a novel lung cancer antigen, LAMR1, which precede onset of symptoms and diagnosis.

Conclusion

Our findings suggest potential utility of an approach to diagnosis of lung cancer before onset of symptoms that includes screening for autoantibodies to defined antigens.
EGFR Mutations Predict Survival Benefit From Gefitinib in Patients With Advanced Lung Adenocarcinoma: A Historical Comparison of Patients Treated Before and After Gefitinib Approval in Japan
Authors: Takano Toshimi , Fukui Tomoya , Ohe Yuichiro , Tsuta Koji , Yamamoto Seiichiro , Nokihara Hiroshi , Yamamoto Noboru , Sekine Ikuo , Kunitoh Hideo , Furuta Koh , Tamura Tomohide
Published: September 2008

Purpose

This study evaluated whether the presence of epidermal growth factor receptor (EGFR) mutations is a predictive marker for survival benefit from gefitinib and/or a prognostic marker in patients with advanced lung adenocarcinoma.

Patients and Methods

Overall survival (OS) was compared between patients with advanced lung adenocarcinoma who began first-line systemic therapy before and after gefitinib approval in Japan (January 1999 to July 2001 and July 2002 to December 2004, respectively). Deletional mutations in exon 19 or the L858R mutation in exon 21 of EGFR were evaluated using high-resolution melting analysis.

Results

EGFR mutations were detected in 136 (41%) of the 330 patients included in this study. OS was significantly longer among the EGFR-mutant patients treated after gefitinib approval compared with the OS of patients treated before gefitinib approval (median survival time [MST], 27.2 v 13.6 months, respectively; P < .001), whereas no significant survival improvement was observed in patients without EGFR mutations (MST, 13.2 v 10.4 months, respectively; P = .13). A significant interaction between the presence of EGFR mutations and a survival improvement was seen (P = .045). Among patients treated before gefitinib approval, those with EGFR mutations lived longer than those without EGFR mutations (MST, 13.6 v 10.4 months, respectively; P = .034). The response rates to first-line cytotoxic chemotherapy were not significantly different between patients with and without EGFR mutations (31% v 28%, respectively; P = .50).

Conclusion

EGFR mutations significantly predict both a survival benefit from gefitinib and a favorable prognosis in patients with advanced lung adenocarcinoma.
Prospective Randomized Study Comparing Docetaxel, Estramustine, and Prednisone With Docetaxel and Prednisone in Metastatic Hormone-Refractory Prostate Cancer
Authors: Machiels Jean-Pascal , Mazzeo Filomena , Clausse Marylene , Filleul Bertrand , Marcelis Luc , Honhon Brigitte , D’Hondt Lionel , Dopchie Catherine , Verschaeve Vincent , Duck Lionel , Verhoeven Didier , Jousten Peter , Bonny Marie-Alix , Moxhon Anne-Marie , Tombal Bertrand , Kerger Joseph
Published: September 2008

Purpose

To assess the efficacy and toxicity of the addition of estramustine to docetaxel (D) for the treatment of metastatic hormone-refractory prostate cancer.

Patients and Methods

One hundred fifty patients were randomly assigned to D alone (35 mg/m2 on days 2 and 9, every 3 weeks) or D in combination with estramustine (D/E; 280 mg orally three times a day on days 1 to 5 and 8 to 12, every 3 weeks). All patients received prednisone (10 mg/d). The primary end point was prostate-specific antigen (PSA) response rate, which was defined as a decrease in PSA ≥ 50% from baseline. The study was powered to test the hypothesis that D/E would improve the PSA response rate by 25%.

Results

The PSA response rate was not statistically different between the two groups. PSA of less than 4 ng/mL occurred in 29 (41%) of 71 patients receiving D/E and in 17 (25%) of 69 patients receiving D (P = .05). No significant differences were found for median time to PSA progression (D/E, 6.9 months; D, 7.3 months) or median overall survival time (D/E, 19.3 months; D, 21 months). More patients had at least one grade 3 or 4 toxicity with D/E (45%) compared with D (21%; P = .005), mainly as a result of grade 3 or 4 GI toxicity (P = .05). Serious adverse events were more frequent with D/E (n = 20) than with D (n = 9; P = .04).

Conclusion

The addition of estramustine to weekly D does not provide any clinically relevant advantage. Both regimens are well tolerated, although the toxicity profile favors D without estramustine.
Outcome After Surgical Resections of Recurrent Chest Wall Sarcomas
Authors: Wouters Michael W. , van Geel Albert N. , Nieuwenhuis Lotte , van Tinteren Harm , Verhoef Cees , van Coevorden Frits , Klomp Houke M.
Published: September 2008

Purpose

Sarcomas of the chest wall are rare, and wide surgical resection is generally the cornerstone of treatment. The objective of our study was to evaluate outcome of full-thickness resections of recurrent and primary chest wall sarcomas.

Patients and Methods

To evaluate morbidity, mortality, and overall and disease-free survival after surgical resection of primary and recurrent chest wall sarcomas, we performed a retrospective review of all patients with sarcomas of the chest wall surgically treated at two tertiary oncologic referral centers between January 1980 and December 2006. Patient, tumor, and treatment characteristics, as well as the follow-up of these patients, were retrieved from the patients’ original records.

Results

One hundred twenty-seven patients were included in this study, 83 patients with a primary sarcoma and 44 patients with a recurrence. Age, sex, tumor size, histologic type, grade and localization on the chest wall were similar for both groups. Fewer neoadjuvant and adjuvant therapies were used in the treatment of recurrences. Chest wall resection was more extensive in the recurrent group, which did not result in more complications (23%) or more reinterventions (5%). Microscopically radical resection was achieved in 80% of the primary sarcomas and 64% of the recurrences. With a median follow-up of 73 months, disease-free survival after surgery for recurrences was 18 months versus 36 months for primary sarcomas, with 5-year survival rates of 50% and 63%, respectively.

Conclusion

Although chances for local control are lower after surgical treatment of recurrent chest wall sarcoma, chest wall resection is a safe and effective procedure, with an acceptable survival.
“GOOD Old Immigrants of Yesteryear,” Who Didn't Learn English: Germans in Wisconsin
Authors: Wilkerson Miranda E. , Salmons Joseph
Published: September 2008

One myth about language and immigration in North America is that nineteenth-century immigrants typically became bilingual almost immediately after arriving, yet little systematic data has been presented for this view. We present quantitative and qualitative evidence about Germans in Wisconsin, where, into the twentieth century, many immigrants and their descendants remained monolingual, decades after immigration had ceased. Even those who claimed to speak English often had limited command. Quantitative data from the 1910 Census, augmented by qualitative evidence from newspapers, court records, literary texts, and other sources, suggest that Germans of various socioeconomic backgrounds often lacked English language skills. German continued to be the primary language in numerous Wisconsin communities, and some second- and third-generation descendants of immigrants were still monolingual as adults. Understanding this history can help inform contemporary debates about language and immigration and help dismantle the myth that successful immigrant groups of yesterday owed their prosperity to an immediate, voluntary shift to English.
The Low-Back Merger in the Steel City: African American English in Pittsburgh
Authors: Eberhardt Maeve
Published: September 2008

This article investigates the status of the low-back vowels in African American English in Pittsburgh, Pennsylvania, where the vowels have been merged since at least the late 1800s. The low-back merger is currently spreading across much of the United States, but to date, its incidence in African American speech has been found to be limited. This article draws from a sample of 34 African Americans native to Pittsburgh. Using data from a word list along with an acoustic analysis of the low-back vowels in conversational speech from sociolinguistic interviews, this article shows that African Americans in Pittsburgh have merged the low-back vowels, thus sharing in this feature of the local phonological system. The article also explores the sociohistorical conditions that facilitated the spread of the merger from white to African American speech in the region.
PARIS Hilton, BRENDA Frazier, Blogs, AND THE PROLIFERATION OFCELEBU-
Authors: Brown David West
Published: September 2008

In 1939, Walter Winchell coined celebutante in recognition of young Brenda Frazier's status and fame. More recently, celebu- has detached and become a productive combining form. Part of that productivity can be ascribed to its felicitous phonological properties. Many celebu- coinages, however, appear in blogs. Thus, the productivity of celebu- results from the specific register conditions of blogs. The specific case of celebu- reveals much about these conditions—the need for semantic economy, the saliency of humor, the function of nominalization, as well as the role of critique and sometimes cruelty. Additionally, celebu- coinages illustrate how blogs have emerged as sites of linguistic innovation.
Grafting Poly(ethylene glycol) to a Glass Surface via a Photocleavable Linker for Light-induced Cell Micropatterning and Cell Proliferation Control
Authors: Kikuchi Yukiko , Nakanishi Jun , Nakayama Hidekazu , Shimizu Takahiro , Yoshino Yutaro , Yamaguchi Kazuo , Yoshida Yasuhiko , Horiike Yasuhiro
Published: September 2008

This paper describes a glass substrate having a photocleavable poly(ethylene glycol) (PEG) designed for light-induced cell micropatterning. The substrate changed from non-cell-adhesive to cell-adhesive by the photocleavage of PEG. Cellular patterns maintained for more than 17 days, and they were able to be changed to control cell migration and proliferation at multi- and single-cell levels by irradiating their adjacent regions during cell cultivation.
Facile Synthesis of Alkyl 1-Oxo-3-phenyl-1H-indene-2-carboxylate through Palladium-catalyzed Carboalkoxylation from 2-Bromo-3-phenylinden-1-ones
Authors: Yum Eul Kgun , Park Woul Seong , Kim Se Hoan , Kang Seung Kyu , Kim Sung Soo , Ahn Jin Hee
Published: September 2008

Palladium-catalyzed carboalkoxylation of 2-bromo-3-phenylindenones in various alcoholic solvents afforded diverse alkyl 1-oxo-3-phenyl-1H-indene-2-carboxylates in high yields.
Coexistence of S–H···O and N–H···O Blue-shifted Hydrogen Bonds in a Small System: HSO···HNO
Authors: Yang Yong
Published: September 2008

Theoretical study indicates that the HSO···HNO complex possesses simultaneously two substantial blue-shifted H bonds: S–H···O and N–H···O. The blue shift of the S(N)–H stretching frequencies is due to an intricate combination of two shortening effects of the electron density decrease in the σ*[S(N)–H] and the rehybridization of spn S(N)–H hybrid orbitals.
Stereospecific Synthesis of sec- and tert-Alkyl Azides from Alcohols and Trimethylsilyl Azide by a New Type of Oxidation–Reduction Condensation Using Phenyl Diphenylphosphinite and Trimethylsilylmethyl Azide
Authors: Mukaiyama Teruaki , Kuroda Kiichi , Maruyama Yuji , Hayashi Yujiro
Published: September 2008

A novel method for the preparation of alkyl azides from alcohols and trimethylsilyl azide by a new type of oxidation–reduction condensation using phenyl diphenylphosphinite and trimethylsilylmethyl azide is described. Chiral secondary and tertiary alcohols are converted into the corresponding chiral azides with almost complete inversion of configuration under mild and neutral conditions.
Fabrication of Hollow Platinum Nanospheres as Electrocatalyst for Conductometric Immunoassay of Interleukin-6 in Human Serum
Authors: Liang Ke-Zhong , Mu Wei-Jun
Published: September 2008

This letter describes the preparation of hollow platinum (Pt) nanospheres as electrocatalyst for conductometric immunoassay of interleukin-6 (IL-6), as a model protein, in human serum.
Efficient Computation of Sparse Hessians Using Coloring and Automatic Differentiation
Authors: Gebremedhin Assefaw H. , Tarafdar Arijit , Pothen Alex , Walther Andrea
Published: September 2008

The computation of a sparse Hessian matrix H using automatic differentiation (AD) can be made efficient using the following four-step procedure: (1) Determine the sparsity structure of H, (2) obtain a seed matrix S that defines a column partition of H using a specialized coloring on the adjacency graph of H, (3) compute the compressed Hessian matrix B ≡ HS, and (4) recover the numerical values of the entries of H from B.

The coloring variant used in the second step depends on whether the recovery in the fourth step is direct or indirect: a direct method uses star coloring and an indirect method uses acyclic coloring. In an earlier work, we had designed and implemented effective heuristic algorithms for these two NP-hard coloring problems. Recently, we integrated part of the developed software with the AD tool ADOL-C, which has recently acquired a sparsity detection capability. In this paper, we provide a detailed description and analysis of the recovery algorithms and experimentally demonstrate the efficacy of the coloring techniques in the overall process of computing the Hessian of a given function using ADOL-C as an example of an AD tool. We also present new analytical results on star and acyclic coloring of chordal graphs. The experimental results show that sparsity exploitation via coloring yields enormous savings in runtime and makes the computation of Hessians of very large size feasible. The results also show that evaluating a Hessian via an indirect method is often faster than a direct evaluation. This speedup is achieved without compromising numerical accuracy.
Stabilizing slow light delay in stimulated Brillouin scattering using a Faraday rotator mirror
Authors: Walker D. R. , Bashkansky M. , Gulian A. , Fatemi F. K. , Steiner M.
Published: September 2008

The delay of the Stokes beam in stimulated Brillouin scattering (SBS) is sensitive to the polarization alignment between the pump and the Stokes. Typically, waveguides exhibit a birefringence that causes beams launched from opposite ends to have fluctuating and suboptimal alignment. We demonstrate in an optical fiber that using a Faraday rotator mirror not only overcomes this problem, but also enhances SBS slow light delay.
Immunolocalization of Ferroportin in Healthy and Anemic Mice
Authors: D'Anna María Cecilia , Veuthey Tania Vanesa , Roque Marta Elena
Published: September 2008

Ferroportin (FPN), the only iron exporter identified to date, participates in iron release from enterocytes and macrophages, regulating its absorption and recycling. We used a murine model of experimental hemolytic anemia to study adaptive changes in the localization of FPN in duodenum, liver, and spleen. FPN was assessed by IHC in healthy and anemic mice using rabbit anti-mouse FPN polyclonal antibodies. Goat-labeled polymer-horseradish peroxidase anti-rabbit Envision+System (DAB) was used as secondary antibody. Tissue iron was studied by Prussian blue iron staining. Anemia evolution and erythropoietic recovery was assessed using conventional hematological tests. Healthy mice showed mainly supra-nuclear expression of FPN in enterocytes and a weak basolateral expression, whereas in anemic mice, the expression was detected mainly at the basolateral membrane (days 4 and 5). Red pulp macrophages of healthy mice showed FPN-hemosiderin colocalization. In the liver of healthy mice, FPN was mainly cytoplasmic, whereas in anemic mice, it was redistributed to the cell membrane. Our findings clearly show that anemia induces adaptive changes in FPN expression, contributing to anemia restoration by increasing available iron. FPN expression in the membrane is the main pathway of iron release. Our data indicate that iron homeostasis in vivo is maintained through the coordinated expression of this iron exporter in both intestinal and phagocytic cells.
Nucleus-Satellite Analysis and Conjugation Mediation in Coptic and Later Egyptian
Authors: Grossmann Eitan
Published: September 2008

The syntactic analysis of the class of elements known as 'preverbal extensions,′ 'conjugation mediators′ or 'preverbals′ is known to be problematic, specifically with regard to nucleus-satellite analysis. In short, it is a matter of debate whether or not the conjugation mediator is to be analyzed as the head of its construction. In the first section of this article, the specific criteria for assessing nuclear status are made explicit, and it is suggested that the conjugation mediators cannot be analyzed as heads or satellites, as for the most part, they do not belong to the verb phrase as such and do not contract a relationship of dependence with the verbal lexeme itself. In the second section, a Demotic construction is analyzed as a pre-Coptic conjugation modifier, closest to Bohairic 'je′. In the third section, some Late Egyptian patterns involving pre-lexemic spatial adverbials are discussed in light of conjugation mediation. The Demotic and Late Egyptian evidence suggests that the phenomenon of conjugation mediation is not an innovation of Coptic, but rather existed as a structural option already in pre-Coptic Egyptian.
A Ramesside Administrative Document (P. Cambridge University Library MS. Add. 4167)
Authors: Hagen Fredrik
Published: September 2008

The article presents a previously unpublished Ramesside administrative papyrus from the Cambridge University Library (P. CUL MS. Add. 4167). The document is a list of food and drink given to various named individuals, mainly controllers and their wives, as well as a stable master, 'by the hand of′ several soldiers. Its social context is not known, but it may be connected with riverbank trading. Photographs, transcription and translation with commentary are included.
Domitian at the Contra-Temple of Karnak
Authors: Klotz David
Published: September 2008

A new translation of the Roman Period inscriptions on the Eighteenth Dynasty contra-temple of Karnak, attached to the rear of the Akh-Menu. These religious texts lead to a reconsideration of the cultic function of this and other contra-temples, previously considered exclusively as locations for popular worship. The inscriptions from the reign of Domitian are primarily solar, associating the contra-temple with the nearby horned altar, sole obelisk, and East temple of Ramesses II, in the section of Karnak called ′the Benben temple.′ The form of Amun in this section was simultaneously ,Amun who hears prayers′ and the newly reborn sundisk who massacres his enemies in the Eastern horizon. The dual role of Amun as healer and punisher (i. e. ,Good Ka, Bad Ka′) combines Heliopolitan theology with the traditional role of gates as places for administering justice, appropriate for the one location where Amun of Karnak could approach the masses, both the faithful and the wicked.
Ambiguous Speech and Eloquent Silence: The Queerness of Tchaikovsky's Songs
Authors: Bullock Philip Ross
Published: September 2008

This article considers a number of Tchaikovsky's songs—specifically those with texts by Apukhtin, Romanov, Heine, Goethe, and Tchaikovsky himself—to explore how silence constitutes a powerful yet elusive form of expression. It argues that Tchaikovsky's songs, an underappreciated and underexplored aspect of his output (at least in the West), are characterized by a degree of literary and musical sophistication seldom attributed to the composer. Their self-consciousness is held to be the product of a combination of three main social and aesthetic forces characteristic of Russian culture in the second half of the nineteenth century. Drawing first on the work of Bakhtin, the article argues that the nature of Tchaikovsky's songs as lyric forms in an age dominated by the realist novel invests them with a creative tension between the need to conceal (an imperative inherited from the lyric poetry of the 1820s and 1830s) and the need to reveal (a feature of the novel's tendency to intimacy and confession). Then, turning to the work of Foucault, it traces how a coherent discourse of homosexual identity (as opposed to an otherwise unrelated series of individual homosexual acts) arose in the later nineteenth century, forcing queer artists to address (whether consciously or otherwise) the question of how best to relate this identity to their creativity. Finally, it looks at the evolving status of the artist in late Imperial Russia and suggests that an uneasy relationship between revealing and concealing was imposed upon personalities in the public eye by an audience that wished to feel close to the artist, yet also required discretion and the avoidance of scandal.

At the heart of the article lies a study of silence as a particularly expressive form of apparent non-expression, dealing with frequent instances in Tchaikovsky's songs of silence as a poetic trope, as well as with equivocation on matters of gender and identity in lyric forms as indicative of a potentially queer sensibility. Also, the article refuses to reimpose a categorically and reductively homosexual reading, posited on some presumed opposed heterosexual norm. Rather, it argues that Tchaikovsky was able to discern the peculiar appeal of lyric forms as referentially incomplete yet aesthetically self-sufficient fragments, and that he approached such lyrics in a way that emphasized qualities of ambiguity, allusion, and the uncanny. Although drawing extensively on literary models, the article also considers how music is paradoxically well placed to enact poetic silence. The relationship between words and music, and between composition, performance, and reception, is a further instance of how song became an apt medium in which the thoughtful composer could explore issues of personal and creative identity in an age of profound artistic and social transformation.