bluuebunny/crossref_metadata_2025 huggingface dataset:
Two‐Dimensional Polymers: Just a Dream of Synthetic Chemists?
Authors: Sakamoto Junji , van Heijst Jeroen , Lukin Oleg , Schlüter A. Dieter
Published: January 2009

In light of the considerable impact synthetic 2D polymers are expected to have on many fundamental and applied aspects of the natural and engineering sciences, it is surprising that little research has been carried out on these intriguing macromolecules. Although numerous approaches have been reported over the last several decades, the synthesis of a one monomer unit thick, covalently bonded molecular sheet with a long‐range ordered (periodic) internal structure has yet to be achieved. This Review provides an overview of these approaches and an analysis of how to synthesize 2D polymers. This analysis compares polymerizations in (initially) a homogeneous phase with those at interfaces and considers structural aspects of monomers as well as possibly preferred connection modes. It also addresses issues such as shrinkage as well as domain and crack formation, and briefly touches upon how the chances for a successful structural analysis of the final product can possibly be increased.
Stable Five‐Membered‐Ring Allenes with Second‐Row Elements Only: Not Allenes, But Zwitterions
Authors: Christl Manfred , Engels Bernd
Published: January 2009

A pyrazole derivative, considered as the stable five‐membered cyclic allene 1 a by Dyker, Bertrand, et al., is reinterpreted to be a zwitterion 1 b. It is shown that the bonding characteristics typical for an allene are not possible for structure 1 a. Ar=2,6‐dimethylphenyl.

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Synthesis of Large‐Pore Urea‐Bridged Periodic Mesoporous Organosilicas
Authors: Gao Ling , Wei Feng , Zhou Yu , Fan Xiao Xing , Wang Ying , Zhu Jian Hua
Published: January 2009

Bringing order: A new class of periodic mesoporous organosilicas (PMOs) with a urea‐bridged organosilica precursor under acid‐catalyzed and inorganic‐salt‐assisted conditions was obtained. The large‐pore hybrid materials have ordered mesostructure with uniform pore size distributions, which can be seen from the TEM images.

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In this article we report the successful synthesis of a new class of periodic mesoporous organosilicas (PMOs) with a urea‐bridged organosilica precursor under acid‐catalyzed and inorganic‐salt‐assisted conditions. The large‐pore hybrid materials have an ordered mesostructure with uniform pore size distributions, excellent thick framework walls, thermal stability, and specific functional groups. The composition of the mesoporous organosilicas was characterized by FTIR spectroscopy, 13C cross‐polarization magic‐angle spinning (CP MAS) NMR spectroscopy, and 29Si MAS NMR spectroscopy.
Capsaicin: Tailored Chemical Defence Against Unwanted “Frugivores”
Authors: Schulze Birgit , Spiteller Dieter
Published: January 2009

Why are chilli peppers hot? The vanillyl amide, capsaicin, has long been known as the pungent principle of peppers, but only in their recent work have Tewksbury et al. addressed its ecological roles: to distract unsuitable seed dispensers and to protect the seeds against fungal infection by Fusarium.

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The Chemistry of Escapin: Identification and Quantification of the Components in the Complex Mixture Generated by an L‐Amino Acid Oxidase in the Defensive Secretion of the Sea Snail Aplysia californica
Authors: Kamio Michiya , Ko Ko‐Chun , Zheng Shilong , Wang Binghe , Collins Stacy L. , Gadda Giovanni , Tai Phang C. , Derby Charles D.
Published: January 2009

A complex mixture of products in an enzymatic reaction: Aplysia californica releases amino acid oxidase and its substrate lysine in defensive secretions to produce a mixture of multiple compounds (see figure).

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Escapin is an L‐amino acid oxidase in the ink of a marine snail, the sea hare Aplysia californica, which oxidizes L‐lysine (1) to produce a mixture of chemicals which is antipredatory and antimicrobial. The goal of our study was to determine the identity and relative abundance of the constituents of this mixture, using molecules generated enzymatically with escapin and also using products of organic syntheses. We examined this mixture under the natural range of pH values for ink—from ≈5 at full strength to ≈8 when fully diluted in sea water. The enzymatic reaction likely forms an equilibrium mixture containing the linear form α‐keto‐ε‐aminocaproic acid (2), the cyclic imine Δ1‐piperidine‐2‐carboxylic acid (3), the cyclic enamine Δ2‐piperidine‐2‐carboxylic acid (4), possibly the linear enol 6‐amino‐2‐hydroxy‐hex‐2‐enoic acid (7), the α‐dihydroxy acid 6‐amino‐2,2‐dihydroxy‐hexanoic acid (8), and the cyclic aminol 2‐hydroxy‐piperidine‐2‐carboxylic acid (9). Using NMR and mass spectroscopy, we show that 3 is the major component of this enzymatic product at any pH, but at more basic conditions, the equilibrium shifts to produce relatively more 4, and at acidic conditions, the equilibrium shifts to produce relatively more 2, 7, and/or 9. Studies of escapin’s enzyme kinetics demonstrate that because of the high concentrations of escapin and L‐lysine in the ink secretion, millimolar concentrations of 3, H2O2, and ammonia are produced, and also lower concentrations of 2, 4, 7, and 9 as a result. We also show that reactions of this mixture with H2O2 produce δ‐aminovaleric acid (5) and δ‐valerolactam (6), with 6 being the dominant component under the naturally acidic conditions of ink. Thus, the product of escapin’s action on L‐lysine contains an equilibrium mixture that is more complex than previously known for any L‐amino acid oxidase.
The extent of minimal residual disease reduction after the first 4‐week imatinib therapy determines outcome of allogeneic stem cell transplantation in adults with Philadelphia chromosome‐positive acute lymphoblastic leukemia
Authors: Lee Seok , Kim Yoo‐Jin , Chung Nak‐Gyun , Lim Jihyang , Lee Dong‐Gun , Kim Hee‐Je , Min Chang‐Ki , Lee Jong‐Wook , Min Woo‐Sung , Kim Chun‐Choo
Published: January 2009

BACKGROUND:

Previously, the authors demonstrated the positive impact of imatinib on the outcome of allogeneic stem cell transplantation in adults with Philadelphia chromosome‐positive acute lymphoblastic leukemia (Ph‐positive ALL). Here, the authors analyzed for risk factors that affect transplantation outcome, and they focused particularly on the prognostic relevance of minimal residual disease level at each treatment stage.

METHODS:

Fifty‐two patients with newly diagnosed Ph‐positive ALL who completed allogeneic stem cell transplantation following imatinib therapy were enrolled in this study. For minimal residual disease monitoring, 548 marrow samples were analyzed by a real‐time quantitative polymerase chain reaction assay.

RESULTS:

After the first 4‐week imatinib therapy, 11 patients (21.2%) achieved molecular remission, and the remaining 41 patients had a reduction in BCR‐ABL transcript levels (median, 3.21 log) from baseline value. The frequency of achieving a reduction in BCR‐ABL transcript levels of at least 3 log at this stage was 36 (69.2%). Forty‐eight (92.3%) of the 52 patients received stem cell transplantation during first complete remission. With a median follow‐up of 49 months after stem cell transplantation, the 4‐year relapse rate and disease‐free survival rate were 21.2% and 69.8%, respectively. A reduction in BCR‐ABL transcript levels of at least 3 log after the first 4‐week imatinib therapy was identified as the most powerful predictor of lower relapse (12.1% vs 45.1%, P = .011) and better disease‐free survival (82.1% vs 41.7%, P = .009) rates.

CONCLUSIONS:

Prospective assessment of the extent of minimal residual disease reduction after the first 4‐week imatinib therapy may allow the authors to identify subgroups of Ph‐positive ALL transplants at high risk of relapse. Cancer 2009. © 2008 American Cancer Society.
Promoting physical activity in childhood cancer survivors
Authors: Cox Cheryl L. , Montgomery Michele , Oeffinger Kevin C. , Leisenring Wendy , Zeltzer Lonnie , Whitton John A. , Mertens Ann C. , Hudson Melissa M. , Robison Leslie L.
Published: January 2009

BACKGROUND:

Although physical activity may modify the late effects of childhood cancer treatment, from 20% to 52% of adult survivors are sedentary. The authors of this report sought to identify modifiable factors that influence survivors' participation in physical activity.

METHODS:

Structural equation modeling of data were derived from the Childhood Cancer Survivors Study of adult survivors (current mean age, 30.98 years; mean years since diagnosis, 23.74; mean age at diagnosis, 9.25 years) who were diagnosed between 1970 and 1986.

RESULTS:

Approximately 40% of the variance in male survivors' recent participation versus nonparticipation in physical activity was explained directly and/or indirectly by self‐reported health fears (P = .01), perceived primary‐care physician (PCP) expertise (P = .01), baseline exercise frequency (P ≤ .001), education level (P = .01), self‐reported stamina (P = .01), cancer‐related pain (P ≤ .001), fatigue (P ≤ .001), age at diagnosis (P = .01), cancer‐related anxiety (P ≤ .001), motivation (P = .01), affect (P = .01), and discussion of subsequent cancer risk with the PCP (P ≤ .001) (N = 256; chi‐square test statistic = 53.38; degrees of freedom [df] = 51; P = .38, Comparative Fit Index [CFI] = 1.000; Tucker Lewis Index [TLI] = 1.000; root mean square of approximation [RMSEA] = 0.014; weighted root mean square residual [WRMR] = 0.76). Thirty‐one percent of the variance in women' recent physical activity participation was explained directly and/or indirectly by self‐reported stamina (P ≤ .001), fatigue (P = .01), baseline exercise frequency (P = .01), cancer‐related pain (P ≤ .001), cancer‐related anxiety (P = .01), recency of visits with PCP (<0.001), quality of interaction with the PCP (P = .01), and motivation (P ≤ .001; N = 366; chi‐square test statistic = 67.52; df = 55; P = .12; CFI = 0.98; TLI = 0.98; RMSEA = 0.025; WRMR = 0.76).

CONCLUSIONS:

Gender‐tailored intervention strategies in which providers specifically target motivation, fear, and affect may support physical activity in childhood cancer survivors. Cancer 2009. © 2008 American Cancer Society.
Meta‐analysis of sentinel lymph node positivity in thin melanoma (≤1 mm)
Authors: Warycha Melanie A. , Zakrzewski Jan , Ni Quanhong , Shapiro Richard L. , Berman Russell S. , Pavlick Anna C. , Polsky David , Mazumdar Madhu , Osman Iman
Published: January 2009

BACKGROUND:

Despite the lack of an established survival benefit of sentinel lymph node (SLN) biopsy, this technique has been increasingly applied in the staging of thin (≤1 mm) melanoma patients, without clear evidence to support this recommendation. The authors performed a meta‐analysis to estimate the risk, potential predictors, and outcome of SLN positivity in this group of patients.

METHODS:

MEDLINE, EMBASE, and Cochrane databases were searched for rates of SLN positivity in patients with thin melanoma. The methodologic quality of included studies was assessed using the Methodological Index for Non‐Randomized Studies criteria. Heterogeneity was assessed using the Cochran Q statistic, and publication bias was examined through funnel plot and the Begg and Mazumdar method. Overall SLN positivity in thin melanoma patients was estimated using the DerSimonial‐Laird random effect method.

RESULTS:

Thirty‐four studies comprising 3651 patients met inclusion criteria. The pooled SLN positivity rate was 5.6%. Significant heterogeneity among studies was detected (P = .005). There was no statistical evidence of publication bias (P = .21). Eighteen studies reported select clinical and histopathologic data limited to SLN‐positive patients (n = 113). Among the tumors from these patients, 6.1% were ulcerated, 31.5% demonstrated regression, and 47.5% were Clark level IV/V. Only 4 melanoma‐related deaths were reported.

CONCLUSIONS:

Relatively few patients with thin melanoma have a positive SLN. To the authors' knowledge, there are no clinical or histopathologic criteria that can reliably identify thin melanoma patients who might benefit from this intervention. Given the increasing diagnosis of thin melanoma, in addition to the cost and potential morbidity of this procedure, alternative strategies to identify patients at risk for lymph node disease are needed. Cancer 2009. © 2008 American Cancer Society.
The volume to be irradiated during selective neck irradiation in nasopharyngeal carcinoma
Authors: Tang Linglong , Mao Yanping , Liu Lizhi , Liang Shaobo , Chen Yong , Sun Ying , Liao Xinbiao , Lin Aihua , Liu Mengzhong , Li Li , Ma Jun
Published: January 2009

BACKGROUND:

For this report, the authors analyzed the spread pattern of lymph node (LN) metastases in patients with nasopharyngeal carcinoma (NPC) by using magnetic resonance imaging (MRI). In addition, the efficacy of selective neck irradiation was assessed based on the volume irradiated.

METHODS:

This was a retrospective review of data from 924 patients with newly diagnosed and nondisseminated NPC who underwent MRI and treatment between January 2003 and December 2004.

RESULTS:

According to the criteria for involved LNs detected by MRI, the incidence of LN metastases was 85.1% (786 of 924 patients). An analysis of the distribution of LN metastases in these 786 patients demonstrated that the retropharyngeal LNs (RLN) and Level II LNs were the most frequently involved regions, followed in order by Level III and Level V LNs, Level IV LNs, and supraclavicular fossa (SCF) LNs. In only 4 of 786 patients (0.5%) did metastasis skip LNs in their progression. In addition, 5 of 354 patients (1.4%) who had unilateral, higher level LN metastases (including RLNs and Level II LNs) had contralateral or bilateral, lower level LN involvement (including Level III, Level IV, Level V, and SCF LNs). In patients who had LN‐negative (N0) disease, the risks of regional recurrence and distant metastasis did not differ statistically between patients with inferior border of the neck irradiation field either at the cricoid cartilage or below the cricoid cartilage.

CONCLUSIONS:

By using MRI, LN metastases spread in an orderly fashion from higher level LNs to lower level LNs. The current results did not support prophylactic irradiation of Level IV and SCF LNs in patients who were negative for LN metastases, and these concepts need to be tested clinically before they may be recommended generally. Cancer 2009. © 2008 American Cancer Society.
Phase 1/2 study of intravenous paclitaxel and oral cyclophosphamide in pretreated metastatic urothelial bladder cancer patients
Authors: Di Lorenzo Giuseppe , Montesarchio Vincenzo , Autorino Riccardo , Bellelli Teresa , Longo Nicola , Imbimbo Ciro , Morelli Emilio , Giannarini Gianluca , Mirone Vincenzo , De Placido Sabino
Published: January 2009

BACKGROUND:

To the authors' knowledge, no previous studies have been reported with the combination of paclitaxel and oral cyclophosphamide in patients with metastatic bladder cancer. A phase 1/2 study was conducted of paclitaxel in combination with oral cyclophosphamide for patients with advanced urothelial bladder cancer who had been previously treated with gemcitabine/cisplatin chemotherapy as first‐line metastatic treatment.

METHODS:

This was a single‐arm phase 1/2 study. Patients were treated with paclitaxel and oral cyclophosphamide at 3‐week intervals until disease progression or irreversible toxicity occurred. Primary endpoints were to determine the maximum tolerated doses (MTD) and objective response rate; secondary endpoints were safety, time to disease progression (TTP), and overall survival (OS).

RESULTS:

Forty‐four patients were enrolled. Dose levels of paclitaxel of 175 mg/m2 (Day 1) and cyclophosphamide of 50 mg (Days 1‐7 orally) (dose level I) of a 21‐day cycle were tolerated without dose‐limiting toxicities (DLTs). At a cyclophosphamide dose of 100 mg (dose level II) the MTD was exceeded; 3 of 6 patients experienced a DLT (grade 3 constipation and grade 4 neutropenia and thrombocytopenia [toxicities were graded using National Cancer Institute Common Toxicity Criteria (version 3.0)]). Dose level I was expanded and determined to be the MTD. A total of 32 patients were treated at dose level I in the phase 2 portion. Partial responses were observed in 31% of patients (10 of 32 patients; 95% confidence interval [95% CI], 17%‐45%). Grade 1/2 vomiting, peripheral neuropathy, and neutropenia were the most common side effects, noted in 11 (34%), 8 (25%), and 10 (31%) patients, respectively. The median TTP was 5 months (95% CI, 2 months‐7.5 months) and the median OS was 8 months (95% CI, 4 months‐14 months).

CONCLUSIONS:

The combination of paclitaxel and cyclophosphamide is well tolerated and associated with promising efficacy. Further trials are needed to confirm these preliminary results. Cancer 2009. © 2008 American Cancer Society.
Esophageal tumor length is independently associated with long‐term survival
Authors: Yendamuri Sai , Swisher Stephen G. , Correa Arlene M. , Hofstetter Wayne , Ajani Jaffer A. , Francis Ashleigh , Maru Dipen , Mehran Reza J. , Rice David C. , Roth Jack A. , Walsh Garrett L. , Vaporciyan Ara A.
Published: January 2009

BACKGROUND:

Esophageal cancer staging uses tumor depth as the sole criterion for assessment of the primary tumor (pT). To the authors' knowledge the impact of esophageal tumor length on long‐term outcome and the esophageal cancer staging system has not been fully evaluated in the current era.

METHODS:

All esophageal cancer patients (n = 209) undergoing surgery from 1995 to 2005 who did not receive preoperative chemotherapy or radiotherapy were reviewed. Maximum esophageal tumor length along a craniocaudal axis was determined pathologically after surgical resection. Univariate and multivariate analyses were used to assess the impact of esophageal tumor length (≤3 cm vs >3 cm) on long‐term survival.

RESULTS:

Esophageal tumor length was closely associated with long‐term survival (hazards ratio [HR] of 6.14 [95% confidence interval (95% CI), 4.1‐9.25]; 5‐year survival: ≤3 cm = 68%, >3 cm = 10% [P < .001]). Multivariate Cox regression analyses demonstrated tumor length (HR of 2.13 [95% CI, 1.26‐3.63]) was found to be a significant independent predictor of long‐term survival even when controlled for sex, age, tumor location, histology, margin positivity, surgical procedure, and current pTNM criteria. The incorporation of tumor length in pTNM staging significantly improves the ability to predict the long‐term survival of patients (5‐year survival for patients with tumors ≤3 cm and stages I, IIA, IIB, and III disease = 86%, 62%, 49%, and 22%, respectively; survival for patients with tumors measuring >3 cm and stages I, IIA, IIB, and III disease = 27%, 22%, 0%, and 8%, respectively [P < .1]).

CONCLUSIONS:

Esophageal tumor length is an independent predictor of long‐term survival in the current era and should be considered for incorporation into the current esophageal cancer staging system to better predict long‐term survival and identify high‐risk patients for postoperative therapy. Cancer 2009. © 2008 American Cancer Society.
Efficacy of imatinib dose escalation in patients with chronic myeloid leukemia in chronic phase
Authors: Kantarjian Hagop M. , Larson Richard A. , Guilhot Francois , O'Brien Stephen G. , Mone Manisha , Rudoltz Marc , Krahnke Tillmann , Cortes Jorge , Druker Brian J. ,   for the International Randomized Study of Interferon and STI571 (IRIS) Investigators
Published: January 2009

BACKGROUND:

Imatinib mesylate given orally at a daily dose of 400 mg is the standard of care as initial therapy for patients with chronic myeloid leukemia (CML) in chronic phase (CML‐CP). Treatment guidelines propose dose escalation based on clinical assessments of disease response.

METHODS:

Response and survival were analyzed in a cohort of patients (n = 106) with newly diagnosed CML‐CP who were enrolled on the International Randomized Study of Interferon and STI571 (IRIS) trial, who began treatment with imatinib at a dose of 400 mg daily, and who subsequently underwent dose escalation to either 600 mg or 800 mg daily. Reasons for dose escalation were evaluated retrospectively based on 2 sets of criteria: the IRIS protocol‐defined criteria (n = 39 patients) and the European LeukemiaNet (ELN) recommendations (n = 48 patients).

RESULTS:

Among all 106 patients who underwent dose escalation, the rates of freedom from progression to accelerated phase or blast phase and overall survival were 89% and 84% at 3 years after dose increase, respectively. A cytogenetic response was obtained in 42% of patients who had their dose escalated based on protocol criteria and in 38% of patients who had their dose escalated according to the ELN recommendations.

CONCLUSIONS:

The results from this retrospective analysis supported imatinib dose escalation as an appropriate initial option for patients with CML‐CP who were experiencing suboptimal cytogenetic response or resistance. Cancer 2009. © 2008 American Cancer Society.
Outcomes of stereotactic radiotherapy for a new clinical stage I lung cancer arising postpneumonectomy
Authors: Haasbeek Cornelis J. A. , Lagerwaard Frank J. , de Jaeger Katrien , Slotman Ben J. , Senan Suresh
Published: January 2009

BACKGROUND:

Resection of second primary lung tumors that arise after previous pneumonectomy is associated with a high risk of complications. In this study, the authors reviewed outcomes after stereotactic radiation therapy (SRT) for such patients.

METHODS:

SRT was undergone by 15 patients who developed a new clinical stage I lung cancer at a median of 8.9 years postpneumonectomy, half of whom had severe chronic obstructive pulmonary disorder (COPD). SRT target volumes encompassed all respiratory motion using 4‐dimensional computed tomography (CT) scans, and risk‐adapted radiation schemes that ranged from 3 × 20 grays (Gy) to 8 × 7.5 Gy were used, depending on tumor size, location, and overlap with prior radiation treatment. All schemes had a biologic effective dose >100 Gy. Follow‐up CT scans were obtained at 3 months, 6 months, and 12 months after SRT and yearly thereafter.

RESULTS:

At a median follow‐up of 16.5 months, no local failures were observed, and only 2 patients experienced grade ≥3 toxicity. One patient had transient pneumonitis that required steroids, and another patient required an increase in oxygen use. The 1‐year actuarial disease‐free survival rate was 92%. One patient died 10 months post‐SRT after developing regional and distant metastases, and 1 patient developed an isolated regional failure. All other patients remained alive and disease free.

CONCLUSIONS:

SRT was a safe and effective treatment for stage I lung tumors that arose after prior pneumonectomy, even in patients who had severe COPD. SRT was tolerated well, and the current findings suggest that surveillance for second tumors is indicated in all patients after pneumonectomy. Cancer 2009. © 2009 American Cancer Society.
Stereotactic radiotherapy for pancreatic cancer?
Authors: Crane Christopher H. , Willett Christopher G.
Published: January 2009

Although the authors of 1 report in this issue have proposed the use of stereotactic body radiotherapy (SBRT) for patients with pancreatic cancer, other authors have associated SBRT with poor outcomes, unacceptable toxicity, and questionable palliative effect. The results of this study do not support the use of SBRT for pancreatic cancer outside of a clinical trial setting.
Survival after hepatic resection of colorectal cancer metastases
Authors: Robertson Douglas J. , Stukel Therese A. , Gottlieb Daniel J. , Sutherland Jason M. , Fisher Elliott S.
Published: January 2009

BACKGROUND:

Most estimates of short‐ and long‐term survival after hepatic resection of colorectal cancer metastases are derived from surgical case series. For the current report, the authors used Medicare data to investigate operative mortality and long‐term survival in a national sample and examined the factors associated with survival.

METHODS:

Data were analyzed from Medicare enrollees (age ≥65 years) who were admitted to hospital between January 1, 2000 and December 31, 2004 with a primary diagnosis of colorectal cancer with resection. The sample was restricted to patients who subsequently underwent hepatic resection for liver metastases. The Medicare Denominator File was used to determine operative mortality and long‐term survival and the factors that were associated with those outcomes.

RESULTS:

Of the 306,061 Medicare beneficiaries who were diagnosed with colorectal cancer, 3957 patients were identified who underwent hepatic resection for liver metastases. The crude 30‐day and 90‐day mortality rates were 4% and 8.2%, respectively, and the 5‐year survival rate was 25.5%. Advancing age (hazards ratio [HR], 1.83; 95% confidence interval [95% CI], 1.32‐2.53 for age ≥80 years vs ages 65‐69 years), comorbid disease (HR, 1.40; 95% CI, 1.06‐1.85 for Charlson ≥5 vs Charlson 0), and synchronous colon/hepatic resection (HR, 2.46; 95% CI, 1.89‐3.20 for synchronous vs metachronous resection) were associated with worse 90‐day mortality. Similarly, long‐term mortality was associated with age (HR, 1.36; 95% CI, 1.18‐1.56), comorbid disease (HR, 1.51; 95% CI, 1.36‐1.69), and synchronous colon/hepatic resection (HR, 1.37; 95% CI, 1.24‐1.51 for synchronous vs metachronous resection).

CONCLUSIONS:

In this national study, short‐ and long‐term survival was worse than that reported in surgical case series. Subgroups at high risk for worse outcomes include the extreme elderly and those undergoing synchronous colon and hepatic resection. Cancer 2009. © 2009 American Cancer Society.
Fragile histidine triad protein, WW domain‐containing oxidoreductase protein Wwox, and activator protein 2γ expression levels correlate with basal phenotype in breast cancer
Authors: Guler Gulnur , Huebner Kay , Himmetoglu Cigdem , Jimenez Rafael E. , Costinean Stefan , Volinia Stefano , Pilarski Robert T. , Hayran Mutlu , Shapiro Charles L.
Published: January 2009

BACKGROUND:

The expression of fragile histidine triad protein (Fhit) and WW domain‐containing oxidoreductase protein (Wwox), tumor suppressors that are encoded by fragile (FRA) loci FRA3B and FRA16D, are lost concordantly in breast cancers. In the current study, the authors examined correlations among Fhit, Wwox, the activator protein 2 transcription factors AP2α and AP2γ, cytokeratins 5 and 6 (CK5/6), epidermal growth factor receptor (EGFR), estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER‐2) and their associations with breast cancer phenotypes.

METHODS:

Tissue microarrays constructed from 837 breast cancer blocks were immunostained. Expression in >10% of tumor cells was considered positive for cytoplasmic CK5/6, membranous EGFR, and nuclear AP2α and AP2γ. Cytoplasmic Fhit and Wwox staining was scored according to staining intensity. ER, PR, and HER‐2 status of tumors was derived from records. Correlations among immunohistochemical markers and tumor subtypes were assessed by univariate and multivariate statistical methods.

RESULTS:

Triple‐negative tumors had more frequent expression of EGFR, CK5/6 (P < .001), and AP2γ (P = .003) and more frequent loss of Fhit and Wwox (P < .001), and an inverse correlation was observed between Fhit, Wwox expression and EGFR, ER, and PR expression (P < .001). Reduced Fhit expression was more common in HER‐2‐positive and AP2γ‐positive cases (P < .001 and P = .002, respectively). There was a direct correlation noted between Fhit and Wwox (P < .001) and a borderline positive relation between AP2α and AP2γ (P = .054).

CONCLUSIONS:

The results from this investigation suggested that reduced expression levels of Fhit, Wwox, and nuclear AP2γ have roles in the pathogenesis of basal‐like differentiation in breast cancer. Alteration in the expression of fragile site genes occurs in most of these cancers and may contribute to defects in DNA repair, as observed in breast cancer 1 (BRCA1)‐deficient cancers. Thus, DNA damage response checkpoint proteins may be targets for treatment. Cancer 2009. © 2009 American Cancer Society.
Evaluation of the use of prophylactic cranial irradiation in small cell lung cancer
Authors: Patel Shilpen , Macdonald O. Kenneth , Suntharalingam Mohan
Published: January 2009

BACKGROUND:

Prophylactic cranial irradiation has been used in patients with small cell lung cancer to reduce the incidence of brain metastasis after primary therapy. The purpose of this study was to evaluate the effects of prophylactic cranial irradiation (PCI) on overall survival and cause‐specific survival.

METHODS:

A total of 7995 patients with limited stage small cell lung cancer diagnosed between 1988 and 1997 were retrospectively identified from centers participating in the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program. Of them, 670 were identified as having received PCI as a component of their first course of therapy. Overall survival and cause‐specific survival were estimated by the Kaplan‐Meier method, comparing patients treated with or without prophylactic whole‐brain radiotherapy. The Cox proportional hazards model was used in the multivariate analysis to evaluate potential prognostic factors.

RESULTS:

The median follow‐up time was 13 months (range, 1 month to 180 months). Overall survival at 2 years, 5 years, and 10 years was 23%, 11%, and 6%, respectively, in patients who did not receive PCI. In patients who received PCI, the 2‐year, 5‐year, and 10‐year overall survival rates were 42%, 19%, and 9%, respectively (P= <.001). The cause‐specific survival rate at 2 years, 5 years, and 10 years was 28%, 15%, 11%, respectively, in patients who did not receive PCI and 45%, 24%, 17%, respectively, in patients who did receive PCI (P= <.001). On multivariate analysis of cause‐specific and overall survival, age at diagnosis, sex, grade, extent of primary disease, size of disease, extent of lymph node involvement, and PCI were found to be significant (P= <.001). The hazards ratios for disease‐specific and all cause mortality were 1.13 and 1.11, respectively, for those not receiving PCI.

CONCLUSIONS:

Significantly improved overall and cause‐specific survival was observed in patients treated with prophylactic cranial irradiation on unadjusted and adjusted analyses. This study concurs with the previously published European experience. Prophylactic cranial irradiation should be considered for patients with limited stage small cell lung cancer. Cancer 2009. © 2008 American Cancer Society.
Real time monitoring of BMP Smads transcriptional activity during mouse development
Authors: Monteiro Rui M. , de Sousa Lopes Susana M. Chuva , Bialecka Monika , de Boer Sophie , Zwijsen An , Mummery Christine L.
Published: January 2009

Sagittal section of a 5‐day‐old mouse kidney expressing a bone morphogenetic protein‐response element:green fluorescent protein (BRE:gfp) transgene. GFP expression detected by immunofluorescence (green) reveals BMP Smad transcriptional activity in the glumeruli and adjacent collecting tubules. See the paper by Monteiro et al., in this issue. (Image provided by Monika Bialecka).
Embryological development of Caiman latirostris (Crocodylia: Alligatoridae)
Authors: Iungman Josefina , Piña Carlos I. , Siroski Pablo
Published: January 2009

Diagram of the head of a day 48 embryo of Caiman latirostris (Crocodylia: Alligatoridea). See the paper by Iungman et al. in this issue.
Macrophages in the embryo and beyond: Much more than just giant phagocytes
Authors: Ovchinnikov Dmitry A.
Published: January 2009

Macrophages in a “MacBlue” mouse embryo at 12 days post coitus, visualized by the expression of enhanced cyan fluorescent protein (ECFP) from a bi‐partite (Csf1r‐Gal4/UAS‐ECFP) transgene. Macrophages are interspersed throughout the embryo, with the highest concentration in the embryonic liver; they are also abundant around the developing heart, brain and eyes. See the review by Ovchinnikov in this issue.
Restraint, hunger, and disinhibition following treatment for binge‐eating disorder
Authors: Downe Kristina A. , Goldfein Juli A. , Devlin Michael J.
Published: January 2009

Objective:

To examine changes in total, flexible and rigid restraint, hunger, and disinhibition in obese individuals with Binge‐Eating Disorder (BED), and assess whether these variables are associated with binge abstinence at post‐treatment and during two‐year follow‐up.

Method:

A total of 116 obese individuals with BED were randomized to a 20‐week treatment trial plus two‐year follow‐up. Using the Eating Inventory (EI), we assessed these factors at pretreatment, post‐treatment, and follow‐up time‐points and examined their relationship to binge abstinence at post‐treatment, 12‐ and 24‐month follow‐up.

Results:

Low disinhibition and high‐total restraint are associated with post‐treatment binge abstinence. There are no significant relationships between post‐treatment EI variables and binge abstinence at 12‐ and 24‐month follow‐up.

Discussion:

Reducing disinhibition as well as increasing EI dietary restraint during BED treatment may be important for short‐term success. © 2009 by Wiley Periodicals, Inc. Int J Eat Disord 2009
D6 and the atypical chemokine receptor family: Novel regulators of immune and inflammatory processes
Authors: Graham Gerard J.
Published: January 2009

Chemokines are key regulators of leukocyte migration and play important roles in a number of physiological and pathological immune and inflammatory contexts. In addition to the classical signalling chemokine receptors there has emerged, recently, a new subclass of atypical chemokine receptors. This subfamily is characterised by an apparent lack of signalling and, in some cases, by an ability to internalise and degrade chemokine ligands. This review describes the family of atypical chemokine receptors with particular emphasis on the D6 receptor. Thein vitroandin vivobiology of D6 is described, which indicates that D6 is active as a scavenger of inflammatory CC‐chemokines and appears to play essential roles in the regulation of inflammatory responses.
Our perception of the mast cell from Paul Ehrlich to now
Authors: Beaven Michael A.
Published: January 2009

Just over a century ago Paul Ehrlich received the Nobel Prize for his studies of immunity. This review describes one of his legacies, the histochemical description of the mast cell, and the research that has ensued since then. After a long period of largely descriptive studies, which revealed little about the biological role of the mast cell, the field was galvanized in the 1950s by the recognition that the mast cell was the main repository of histamine and a key participant in anaphylactic reactions. Although the mast cell was long‐viewed in these terms, recent research has now shown that the mast cell also plays a key role in innate and adaptive immune responses, autoimmune disease, and possibly tissue homeostasis by virtue of its expression of a diverse array of receptors and biologically active products. In addition, the responsiveness of mast cells to immunological and pathological stimulants is highly modulated by the tissue cytokine environment and by synergistic, or inhibitory, interactions among the various mast cell receptor systems. This once enigmatic cell of Paul Ehrlich has proved to be both adaptable and multifunctional.
Fatty acid composition in wild and cultivated pacu and pintado fish
Authors: Tanamati Augusto , Stevanato Flávia Braidotti , Visentainer Jeane Eliete Laguila , Matsushita Makoto , de Souza Nilson Evelázio , Visentainer Jesuí Vergílio
Published: January 2009

The fatty acid compositions of muscle tissue taken from wild strains of pintado (Pseudoplatystoma corruscans) and pacu (Piaractus mesopotamicus) fish, which were taken from the Brazilian Pantanal, were compared to the fatty acid compositions of tissue taken from two corresponding cultivated strains, which were fed commercial diets. The cultivated species possessed lipid contents of 12.2% (pacu) and 8.9% (pintado) while the wild species contained 7.9% (pacu) and 2.5% (pintado) lipids. Despite the high lipid contents of the cultivated pintado and pacu, the n‐3 polyunsaturated fatty acid concentrations in muscle tissue were higher in wild pintado (224.9 mg/g flesh) and wild pacu (485.1 mg/g flesh) than in their respective cultivated strains (129.8 and 106.1 mg/g flesh, respectively). The n‐6/n‐3 ratios of pacu were 1.2 (wild) and 9.8 (cultivated), and those of pintado were 1.0 (wild) and 7.3 (cultivated). The fatty acid composition of pacu and pintado are strongly influenced by habitat and diet.
Chemically and enzymatically catalyzed synthesis of C6–C10 alkyl benzoates
Authors: Krause Przemyslaw , Hilterhaus Lutz , Fieg Georg , Liese Andreas , Bornscheuer Uwe
Published: January 2009

The esterification of benzoic acid with n‐hexanol, n‐octanol, 2‐ethyl hexanol and n‐decanol was investigated in detail. An analysis of the reaction kinetics of esterification in the presence of different commercially available chemical catalysts was carried out. The effects of catalyst type and loading on the reaction rate were studied. Although the considered reaction is bimolecular, it showed a first‐order behavior, and a linear dependence with respect to the catalyst concentration was observed. Hence, a new approach is presented to describe the reaction kinetics accurately over a wide range. The application of biotechnological synthesis applying different enzymes as catalysts offers an interesting alternative besides chemical synthesis. Especially an esterase from Bacillus subtilis immobilized on Sepabeads EC‐EP showed high stability and was applied for 2 days in the synthesis of hexyl benzoate. Nevertheless, the chemical reaction route remains superior with respect to the catalyst activities under the applied conditions, which were 25 kU/g for the chemical reaction and 0.7 kU/g for the best enzymatic conversion.
Antioxidant activity and free radical‐scavenging capacity of ethanolic extracts of thyme, oregano, and marjoram
Authors: Amarowicz Ryszard , Żegarska Zofia , Rafałowski Ryszard , Pegg Ronald B. , Karamać Magdalena , Kosińska Agnieszka
Published: January 2009

Phenolic compounds were extracted from thyme (Thymus vulgaris L.), oregano (Origanum vulgare L.) and marjoram (Origanum majorana L.) with 95% ethanol. A number of antioxidant and radical‐scavenging capacity tests were performed on the prepared extracts using colorimetric assays and model system studies. Specifically, these included determining the content of total phenolics, antioxidant efficacy in a linoleic acid‐ferric thiocyanate model system, reducing power, scavenging effect on 2,2'‐diphenyl‐1‐picrylhydrazyl radical, and hydroxyl radical‐scavenging activity by electron paramagnetic resonance spectroscopy. Moreover, the efficacies of the prepared herb extracts were investigated in a real‐life food product: the stabilization of butter against oxidation.
Photochemical Reactivity of 2‐Azido‐1,3‐thiazole and 2‐Azido‐1,3‐benzothiazole: A Procedure for the Aziridination of Enol Ethers
Authors: D'Auria Maurizio , Racioppi Rocco , Viggiani Licia , Zanirato Paolo
Published: January 2009

Direct irradiation of a mixture of the azido–tetrazole tautomers of 2‐azido‐1,3‐thiazole and 2‐azido‐1,3‐benzothiazole in toluene solution gives products arising from the intermediate nitrene, which in turn undergoes ring opening in the case of 2‐azido‐1,3‐thiazole to give a polymer, and dimerization in the case of 2‐azido‐1,3‐benzothiazole to give [1,3]benzothiazolo[2′,3′:3,4][1,2,4,5]tetraazino[6,1b][1,3]benzothiazolein low yields. When irradiation is performed in the presence of methyl acrylate or various enol ethers, aziridination of the double bond is observed, with good yields in the case of enol ethers. Among these, 1‐(6‐methyl‐3,4‐dihydro‐2H‐pyran‐2‐yl)ethanone undergoes aziridination with complete diastereoselectivity to give the (1RS,3RS,6SR) diastereomer.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
New Bioactive 2,3‐Epoxycyclohexenes and Isocoumarins from the Endophytic Fungus Phomopsis sp. from Laurus Azorica
Authors: Hussain Hidayat , Akhtar Nadeem , Draeger Siegfried , Schulz Barbara , Pescitelli Gennaro , Salvadori Piero , Antus Sándor , Kurtán Tibor , Krohn Karsten
Published: January 2009

Six new metabolites, namely cycloepoxylactone (1a), cycloepoxytriol A (2), cycloepoxytriol B (3) and phomolactones A–C (4–6), were isolated from two cultures of the ethyl acetate soluble fraction of the endophytic fungus Phomopsis sp. (internal strain no. 7233). Their structures were determined by means of spectroscopic data including HREIMS, 1H NMR, 13C NMR, and 2D NMR (HMQC, HMBC, and NOESY). The absolute configurations of 1a, 4 and 5 were determined by circular dichroism and comparison of solution CD spectra with TDDFT‐calculated ones. Preliminary studies showed that cycloepoxylactone (1a) has good antibacterial, antifungal, and algicidal activity against Bacillus megaterium, Microbotryum violaceum, and Chlorella fusca, respectively, whereas cycloepoxytriol B (3) has good algicidal activity against Chlorella fusca.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Development of a CE‐MS2 method for the enantiomeric separation of L/D‐carnitine: Application to the analysis of infant formulas
Authors: Castro‐Puyana María , García‐Ruiz Carmen , Crego Antonio L. , Marina Maria Luisa
Published: January 2009

A new chiral analytical method based on CE‐MS is proposed for the identification and simultaneous quantification of D/L‐carnitine in infant formulas. Previous derivatization of carnitine with FMOC enabled the optimization of the chiral separation using CE with UV detection. An optimization of electrospray‐MS parameters using a partial filling of the non‐volatile chiral selector (succinyl‐γ‐CD) was performed. A selective fragmentation using MS2 experiments with an ion trap analyser was carried out to confirm the identity of D/L‐carnitine according to the current legislation. Satisfactory results were obtained in terms of linearity, precision, and accuracy. Interestingly, the CE‐MS2 method developed allowed a sensitivity enhancement with respect to UV detection of 100‐fold, obtaining an LOD of 100 ng/g for D‐carnitine. The determination of L‐carnitine and its enantiomeric purity in 14 infant formulas supplemented with carnitine was successfully achieved, sample preparation only requiring an ultrafiltration with centrifugal filter devices to retain the components with the highest molecular weights.
Generating high peak capacity 2‐D maps of complex proteomes using PMMA microchip electrophoresis
Authors: Osiri John K. , Shadpour Hamed , Park Sunjung , Snowden Brandy C. , Chen Zhi‐Yuan , Soper Steven A.
Published: January 2009

A high peak capacity 2‐D protein separation system combining SDS micro‐CGE (SDS μ‐CGE) with microchip MEKC (μ‐MEKC) using a PMMA microfluidic is reported. The utility of the 2‐D microchip was demonstrated by generating a 2‐D map from a complex biological sample containing a large number of constituent proteins using fetal calf serum (FCS) as the model system. The proteins were labeled with a thiol‐reactive AlexaFluor 633 fluorophore (excitation/emission: 633/652 nm) to allow for ultra‐sensitive on‐chip detection using LIF following the 2‐D separation. The high‐resolution separation of the proteins was accomplished based on their size in the SDS μ‐CGE dimension and their interaction with micelles in the μ‐MEKC dimension. A comprehensive 2‐D SDS μ‐CGE×μ‐MEKC separation of the FCS proteins was completed in less than <30 min using this 2‐D microchip format, which consisted of 60 mm and 50 mm effective separation lengths for the first and second separation dimensions, respectively. Results obtained from the microchip separation were compared with protein maps acquired using conventional 2‐D IEF and SDS‐PAGE of a similar FCS sample. The microchip 2‐D separation was found to be ∼60× faster and yielded an average peak capacity of 2600 (±149), nearly three times larger than that obtained using conventional IEF/SDS‐PAGE.
Cognitive‐behavioural therapy for individuals with bulimia nervosa and a co‐occurring substance use disorder
Authors: Sysko Robyn , Hildebrandt Tom
Published: January 2009

A significant percentage of individuals with bulimia nervosa (BN) also can be diagnosed with a co‐occurring substance use disorder (SUD). Although studies have addressed the frequency of overlap between the disorders, etiology and shared personality traits, limited research is available about the treatment of these comorbid patients. Adapting cognitive‐behaviour therapy (CBT) to serve as an integrated treatment for patients with both BN and a SUD is a viable option, as studies of CBT suggest that this form of treatment is efficacious for both disorders independently. The shared strategies in CBT for BN and SUDs facilitate the development of a combined treatment for individuals with both disorders with the addition of modules designed to address some common features of these disorders, such as motivation, difficulty with interpersonal relationships, reward sensitivity and impulsivity. Future research should begin to evaluate the efficacy of an integrated CBT in treating individuals with BN and a SUD. Copyright © 2009 John Wiley & Sons, Ltd and Eating Disorders Association.
Defective inhibition and inter‐regional phase synchronization in pianists with musician's dystonia: An EEG study
Authors: Herrojo Ruiz María , Senghaas Patricia , Grossbach Michael , Jabusch Hans‐Christian , Bangert Marc , Hummel Friedhelm , Gerloff Christian , Altenmüller Eckart
Published: January 2009

Recent neurophysiological studies have associated focal‐task specific dystonia (FTSD) with impaired inhibitory function. However, it remains unknown whether FTSD also affects the inhibition (INH) of long‐term overlearned motor programs. Consequently, we investigated in a Go/NoGo paradigm the neural correlates associated with the activation (ACT) and inhibition of long‐term overlearned motor memory traces in pianists with musician's dystonia (MD), a form of FTSD, during a relevant motor task under constraint timing conditions with multichannel EEG. In NoGo trials, the movement related cortical potentials showed a positive shift after the NoGo signal related to inhibition and was significantly smaller over sensorimotor areas in musicians with MD. Further, we observed an increase at 850–900 ms in the power of beta oscillations which was significantly weaker for the patient group. The role of the inter‐electrode phase coupling in the sensorimotor integration of inhibitory processes turned out to be the most relevant physiological marker: the global phase synchronization during INH exhibited an increase between 230 and 330 ms and 7–8 Hz, increase which was significantly smaller for pianists with MD. This effect was due to a weaker phase synchronization between the supplementary motor cortex and left premotor and sensorimotor electrodes in patients. Thus, our findings support the hypothesis of a deficient phase coupling between the neuronal assemblies required to inhibit motor memory traces in patients with MD. EMG recorded from the right flexor pollicis longus muscle confirmed that patients with MD had a disrupted INH in NoGo trials. Hum Brain Mapp 2009. © 2008 Wiley‐Liss, Inc.