bluuebunny/crossref_metadata_2025 huggingface dataset:
Geographic variation of racial/ethnic disparities in colorectal cancer testing among medicare enrollees
Authors: Semrad Thomas J. , Tancredi Daniel J. , Baldwin Laura‐Mae , Green Pamela , Fenton Joshua J.
Published: January 2011

BACKGROUND:

The Medicare population has documented racial/ethnic disparities in colorectal cancer (CRC) screening, but it is unknown whether these disparities differ across geographic regions.

METHODS:

Among Medicare enrollees within 8 US states, we ascertained up‐to‐date CRC screening on December 31, 2003 (fecal occult blood testing in the prior year or sigmoidoscopy or colonoscopy in the prior 5 years). Logistic regression models tested for regional variation in up‐to‐date status among white versus different nonwhite populations (blacks, Asian/Pacific Islanders [APIs], Hispanics). We estimated regression‐adjusted region‐specific prevalence of up‐to‐date status by race/ethnicity and compared adjusted white versus nonwhite up‐to‐date prevalence across regions by using generalized least squares regression.

RESULTS:

White versus nonwhite up‐to‐date status varied significantly across regions for blacks (P = .01) and APIs (P < .001) but not Hispanics (P = .62). Whereas the white versus black differences in proportion up‐to‐date were greatest in Atlanta (Georgia), rural Georgia, and the San Francisco Bay Area of California (range, 10%‐16% differences, blacks<whites); there were no significant white versus black differences in Connecticut, Seattle (Washington) or Iowa. Whereas APIs had significantly lower up‐to‐date prevalence than whites in Michigan and the California regions of San Francisco, Los Angeles, and San Jose (range, 4%‐15% differences, APIs<whites), APIs in Hawaii had higher up‐to‐date status than whites (52% vs 38% P < .001). White versus Hispanic differences were substantial but homogeneous across regions (range, 8%‐16% differences, Hispanics<whites). In contrast to nonwhites, there was little geographic variation in up‐to‐date status among whites.

CONCLUSIONS:

Significant geographic variation in up‐to‐date status among black and API Medicare enrollees is associated with heterogeneous racial/ethnic disparities for these groups across US regions. Cancer 2011. © 2011 American Cancer Society.
Outcomes of malignant tumors of the lacrimal apparatus
Authors: Skinner Heath D. , Garden Adam S. , Rosenthal David I. , Ang K. Kian , Morrison William H. , Esmaeli Bita , Pinnix Chelsea C. , Frank Steven J.
Published: January 2011

BACKGROUND:

Malignant epithelial neoplasms of the lacrimal apparatus are rare and are typically treated with surgery and occasionally adjuvant radiation therapy (RT). The purpose of this study was to assess treatment outcomes by type of surgery (orbital exenteration vs eye‐sparing surgery) and clarify the role of adjuvant RT for this rare disease.

METHODS:

Forty‐six patients with malignant epithelial neoplasms of the lacrimal apparatus were treated at a single institution from 1945 through 2008. Twenty‐seven patients (59%) were treated with orbital exenteration and 19 (41%) with eye‐sparing surgery; 64% of the orbital exenteration group and 83% of the eye‐sparing surgery group also received adjuvant RT (median dose, 60 grays). Median follow‐up time for all patients was 38 months (range, 3‐460 months).

RESULTS:

For the orbital exenteration and eye‐sparing surgery groups, the 5‐year overall survival (OS) rates were 59% and 62%, and the 5‐year disease‐free survival (DFS) rates were 49% and 39%, respectively (P = .56, P = .35). Tumor status (T1‐2 vs T3‐4) was associated with OS (P = .02), and tumor size (<3.5 vs >3.5 cm) with DFS (P = .015). Median time to locoregional recurrence was 85 months for orbital exenteration, and 123 months for eye‐sparing surgery. All patients who did not receive RT experienced local recurrence, and RT extended time to locoregional recurrence (median 460 vs 30 months, P = .009). Seven grade ≥3 complications were experienced after adjuvant RT.

CONCLUSIONS:

For appropriately selected patients, an eye‐sparing surgery for lacrimal apparatus tumors can achieve similar survival outcomes to those in patients treated with an orbital exenteration. Adjuvant RT should be considered for all patients presenting with these rare tumors. Cancer 2011. © 2011 American Cancer Society.
Correlation of LAPTM4B polymorphisms with cervical carcinoma
Authors: Meng Fanling , Song Hongtao , Luo Chang , Yin Mingzhu , Xu Ye , Liu Haixia , Zhou Rouli , Lou Ge
Published: January 2011

BACKGROUND:

Lysosome‐associated protein transmembrane 4 beta (LAPTM4B), a novel oncoprotein, is overexpressed in several carcinomas. Previous studies revealed that LAPTM4B polymorphisms contribute to the risk of certain types of cancers. The purpose of this study was to investigate the association between different LAPTM4B alleles and the risk of cervical carcinoma.

METHODS:

A case‐control analysis was performed in 317 patients with cervical cancer and 416 control subjects. Genomic DNA was extracted from peripheral blood lymphocytes in all participants. LAPTM4B genotypes were determined using polymerase chain reaction. Odds ratios and 95% confidence intervals (CIs) were computed using an unconditional logistic regression model.

RESULTS:

There was a significant difference (P<.001) in LAPTM4B*2 allele frequency between cervical cancer cases (35.8%) and controls (26.3%). There was also a significant difference in the overall genotypic distribution between patients and controls (P < .001). Using the LAPTM4B*1/1 genotype as a reference, we found that LAPTM4B allelic variation was associated with a significantly increased risk of cervical cancer, with adjusted odds ratios of 1.60 (95% CI, 1.15‐2.22) and 2.12 (95% CI, 1.20‐3.76) for the *1/2 and *2/2 genotype, respectively. Stratification analysis indicated that the association was more pronounced in younger subjects, smokers, premenopausal women, and women with more parities. Moreover, multiplicative joint effects were found between the *1/2 or *2/2 genotype and smoking.

CONCLUSIONS:

The findings of this study indicated that the LAPTM4B*2 allele might be a cervical cancer risk factor and may play an important role in genetic susceptibility to cervical cancer in the Chinese population. Cancer 2011. © 2011 American Cancer Society.
Survival after complete surgical resection of multiple metastases from renal cell carcinoma
Authors: Alt Angela L. , Boorjian Stephen A. , Lohse Christine M. , Costello Brian A. , Leibovich Bradley C. , Blute Michael L.
Published: January 2011

BACKGROUND:

Although a role for resection of solitary metastases from renal cell carcinoma (RCC) has been described, the utility of surgery in patients with multiple sites of disease has been less well defined. The authors report the survival of patients who underwent complete metastasectomy for multiple RCC metastases.

METHODS:

The authors identified 887 patients who underwent nephrectomy for RCC between 1976 and 2006 who developed multiple metastatic lesions. The impact of complete metastasectomy on survival was evaluated controlling for the timing, location, and number of metastases and for patient performance status.

RESULTS:

Of 887 patients, 125 (14%) underwent complete surgical resection of all metastases. Complete metastasectomy was associated with a significant prolongation of median cancer‐specific survival (CSS) (4.8 years vs 1.3 years; P < .001). Patients who had lung‐only metastases had a 5‐year CSS rate of 73.6% with complete resection versus 19% without complete resection (P < .001). A survival advantage from complete metastasectomy also was observed among patients with multiple, nonlung‐only metastases, who had a 5‐year CSS rate of 32.5% with complete resection versus 12.4% without complete resection (P < .001). Complete resection remained predictive of improved CSS for patients who had ≥3 metastatic lesions (P < .001) and for patients who had synchronous (P < .001) and asynchronous (P = .002) multiple metastases. Moreover, on multivariate analysis, the absence of complete metastasectomy was associated significantly with an increased risk of death from RCC (hazard ratio, 2.91; 95% confidence interval, 2.17‐3.90; P < .001).

CONCLUSIONS:

The current results indicated that complete resection of multiple RCC metastases may be associated with long‐term survival and should be considered when technically feasible in appropriate surgical candidates. Cancer 2011. © 2011 American Cancer Society.
miR‐340 inhibition of breast cancer cell migration and invasion through targeting of oncoprotein c‐Met
Authors: Wu Zheng‐sheng , Wu Qiang , Wang Chao‐qun , Wang Xiao‐nan , Huang Jing , Zhao Jing‐jing , Mao Shan‐shan , Zhang Gui‐hong , Xu Xiao‐chun , Zhang Nong
Published: January 2011

BACKGROUND:

Different microRNAs have been shown to have oncogenic and tumor‐suppressive functions in human cancers. Detection of their expression may lead to identifying novel markers for breast cancer.

METHODS:

The authors detected miR‐340 expression in 4 human breast cell lines and then focused on its role in regulation of tumor cell growth, migration, and invasion and target gene expression. They then analyzed miR‐340 expression in benign and cancerous breast tissue specimens.

RESULTS:

Endogenous miR‐340 expression was down‐regulated in the more aggressive breast cancer cell lines, which was confirmed in breast cancer tissue specimens by using quantitative real‐time polymerase chain reaction. Further studies showed that induction of miR‐340 expression was able to suppress tumor cell migration and invasion, whereas knockdown of miR‐340 expression induced breast cancer cell migration and invasion. At the gene level, the authors identified c‐Met as a direct miR‐340 target to mediate cell migration and invasion through regulation of MMP‐2 and MMP‐9 expression. Ex vivo, loss of miR‐340 expression was associated with lymph node metastasis, high tumor histological grade, clinical stage, and shorter overall survival of breast cancer as well as increased c‐Met expression in breast cancer tissue specimens.

CONCLUSIONS:

miR‐340 may play an important role in breast cancer progression, suggesting that miR‐340 should be further evaluated as a novel biomarker for breast cancer metastasis and prognosis, and potentially a therapeutic target. Cancer 2011. © 2011 American Cancer Society.
Cucurbitacin I inhibits tumorigenic ability and enhances radiochemosensitivity in nonsmall cell lung cancer‐derived CD133‐positive cells
Authors: Hsu Han‐Shui , Huang Pin‐I , Chang Yuh‐Lih , Tzao Ching , Chen Yi‐Wei , Shih Hsin‐Chin , Hung Shih‐Chieh , Chen Yu‐Chih , Tseng Ling‐Ming , Chiou Shih‐Hwa
Published: January 2011

BACKGROUND:

Signal transducer and activator of transcription 3 (STAT3) signaling reportedly promotes tumor malignancy and recurrence in nonsmall cell lung cancer (NSCLC). It was demonstrated previously that the STAT3 pathway maintains the tumorigenicity and therapeutic resistance of malignant tumors as well as cancer stem cells (CSCs). The objective of the current study was to investigate the effect of the strong STAT3 inhibitor, cucurbitacin I, in prominin‐1 (CD133)‐positive lung cancer cells.

METHODS:

CD133‐positive and CD133‐negative NSCLC‐derived cells were isolated from 7 patients with NSCLC. CD133‐positive NSCLC cells that were treated with or without cucurbitacin I were evaluated for their expression of phosphorylated STAT3 (p‐STAT3), tumorigenicity, stemness properties, and resistance to chemotherapeutic drugs and ionizing radiation.

RESULTS:

Compared with parental or CD133‐negative NSCLC cells, CD133‐positive NSCLC cells had greater tumorigenicity, greater radioresistance, and higher expression of octamer‐binding transcription factor 4 (Oct‐4), Nanog homeobox, and sex‐determining region Y, box 2 (Sox2) at high p‐STAT3 levels. Cucurbitacin I treatment at 100 nM effectively abrogated STAT3 activation, tumorigenic capacity, sphere formation ability, radioresistance, and chemoresistance in CD133‐positive NSCLC cells. Microarray data suggested that cucurbitacin I inhibited the stemness gene signature of CD133‐positive NSCLC cells and facilitated the differentiation of CD133‐positive NSCLC cells into CD133‐negative NSCLC cells. It is noteworthy that 150 nM cucurbitacin I effectively blocked STAT3 signaling and downstream survival targets, such as B‐cell chronic lymphocytic leukemia/lymphoma 2 (Bcl‐2) and Bcl‐2‐like 1 (Bcl‐xL) expression and induced apoptosis in CD133‐positive NSCLC cells. Finally, xenotransplantation experiments revealed that cucurbitacin I plus radiotherapy or chemotherapeutic drugs significantly suppressed tumorigenesis and improved survival in NSCLC‐CD133‐positive‐transplanted, immunocompromised mice.

CONCLUSIONS:

Targeting STAT3 signaling in CD133‐positive NSCLC cells with cucurbitacin I suppressed CSC‐like properties and enhanced chemoradiotherapy response. The potential of cucurbitacin I should be verified further in future anti‐CSC therapy. Cancer 2011. © 2011 American Cancer Society.
Studying cancer in minorities
Authors: Olson Sara H. , Layne Tracy M. , Simon Jennifer A. , Ludwig Emmy , O'Reilly Eileen , Allen Peter J. , Kurtz Robert C.
Published: January 2011

BACKGROUND:

Inclusion of minorities is an important but challenging aspect of epidemiologic studies in the United States. One aspect of this challenge that has received little attention is the actual number of minorities with specific cancers. The authors aimed to understand how population characteristics affect the numbers of minority cancer cases in Surveillance, Epidemiology, and End Results (SEER) regions.

METHODS:

By using SEER data, the authors identified 6 cancers with higher incidence rates in racial and ethnic minorities and reviewed the annual number of cases of those cancers in SEER areas where there are large numbers of blacks, Hispanics, and Asians. The authors examined the age characteristics of the populations in SEER areas using data from the US Census.

RESULTS:

Although there are substantial numbers of cases for the most common cancers with higher incidence in blacks, their numbers are quite small for other cancers, <150 cases, and in many areas, <100 per year. Few registries have substantial numbers of Hispanics or Asians. As expected, the proportion of minority populations is lower in older age groups, whereas the proportion of non‐Hispanic whites is larger.

CONCLUSIONS:

Because of the sharp decline in minority populations associated with age and the high age‐specific incidence rates of most cancers, the actual number of minority cases is quite small for several cancers. Thus, the inclusion of minority groups in studies of any but the most common cancers presents a challenge. Cancer 2011. © 2011 American Cancer Society.
High‐intensity focused ultrasound (HIFU) is not indicated for treatment of primary bone sarcomas
Authors: Bielack Stefan S. , Marina Neyssa , Bernstein Mark
Published: January 2011

Surgery is the method of choice for local treatment of osteosarcoma. Experimental approaches should not be considered “safe” unless they are proven to produce equivalent local control rates.
Long‐term survival after radical prostatectomy versus external‐beam radiotherapy for patients with high‐risk prostate cancer
Authors: Boorjian Stephen A. , Karnes R. Jeffrey , Viterbo Rosalia , Rangel Laureano J. , Bergstralh Eric J. , Horwitz Eric M. , Blute Michael L. , Buyyounouski Mark K.
Published: January 2011

BACKGROUND:

The long‐term survival of patients with high‐risk prostate cancer was compared after radical prostatectomy (RRP) and after external beam radiation therapy (EBRT) with or without adjuvant androgen‐deprivation therapy (ADT).

METHODS:

In total, 1238 patients underwent RRP, and 609 patients received with EBRT (344 received EBRT plus ADT, and 265 received EBRT alone) between 1988 and 2004 who had a pretreatment prostate‐specific antigen (PSA) level ≥ 20 ng/mL, a biopsy Gleason score between 8 and 10, or clinical tumor classification ≥ T3. The median follow‐up was 10.2 years, 6.0 years, and 7.2 years after RRP, EBRT plus ADT, and EBRT alone, respectively. The impact of treatment modality on systemic progression, cancer‐specific survival, and overall survival was evaluated using multivariate Cox proportional hazard regression analysis and a competing risk‐regression model.

RESULTS:

The 10‐year cancer‐specific survival rate was 92%, 92%, and 88% after RRP, EBRT plus ADT, and EBRT alone, respectively (P = .06). After adjustment for case mix, no significant differences in the risks of systemic progression (hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.51‐1.18; P = .23) or prostate cancer death (HR, 1.14; 95% CI, 0.68‐1.91; P = .61) were observed between patients who received EBRT plus ADT and patients who underwent RRP. The risk of all‐cause mortality, however, was greater after EBRT plus ADT than after RRP (HR, 1.60; 95% CI, 1.25‐2.05; P = .0002).

CONCLUSIONS:

RRP alone and EBRT plus ADT provided similar long‐term cancer control for patients with high‐risk prostate cancer. The authors concluded that continued investigation into the differing impact of treatments on quality‐of‐life and noncancer mortality will be necessary to determine the optimal management approach for these patients. Cancer 2011. © 2011 American Cancer Society.
Assessing the clinical benefit of nuclear matrix protein 22 in the surveillance of patients with nonmuscle‐invasive bladder cancer and negative cytology
Authors: Shariat Shahrokh F. , Savage Caroline , Chromecki Thomas F. , Sun Maxine , Scherr Douglas S. , Lee Richard K. , Lughezzani Giovanni , Remzi Mesut , Marberger Michael J. , Karakiewicz Pierre I. , Vickers Andrew J.
Published: January 2011

BACKGROUND:

Several studies have demonstrated that abnormal levels of nuclear matrix protein 22 (NMP22) are associated with bladder cancer and have led to the approval of NMP22 as a urinary biomarker by the US Food and Drug Administration. Nonetheless, the clinical significance of NMP22 remains unclear. The objective of this study was to use decision analysis to determine whether NMP22 improves medical decision‐making.

METHODS:

The current study included 2222 patients who had a history of nonmuscle‐invasive bladder cancer and current negative cytology. The authors developed models to predict cancer recurrence or progression to muscle‐invasive disease using voided NMP22 levels, cystoscopy, age, and sex. Clinical net benefit was calculated by summing the benefits (true‐positives), subtracting the harms (false‐positives), and weighting these values by the threshold probability at which a patient or clinician would opt for cytoscopy.

RESULTS:

After cystoscopy, 581 patients (26%) had cancer identified. The NMP22 level was associated significantly with bladder cancer recurrence and progression (P < .001 for both). The use of NMP22 in a model with age and sex was associated with better patient outcomes than performing cystoscopy on everyone and produced threshold probabilities > 8% for recurrence and > 3% for progression. Only offering cystoscopy to those who had a risk > 15% reduced the number of cystoscopies by 229 while missing only 25 cancer recurrences per 1000 men with negative cytology. The current study was limited by its multicenter design.

CONCLUSIONS:

For clinicians who would perform a cystoscopy at a threshold of 5% for recurrence or 1% for progression, NMP22 did not aid clinical decision‐making. For less risk‐averse clinicians who would only perform a cystoscopy at a threshold probability >thinsp;8% for recurrence or > 3% for progression, NMP22 helped to indicate which patients required cystoscopy and which could be spared this procedure. Cancer 2011. © 2011 American Cancer Society.
Pulmonary Circulation in Extreme Environments
Authors: Prisk G. Kim
Published: January 2011

The pulmonary circulation is subject to direct challenge from both altered pressure and altered gravity. To efficiently exchange gas, the pulmonary capillaries must be extremely thin‐walled and directly exposed to the alveolar space. Thus, alterations in ambient pressure are directly transmitted to the capillaries with the potential to alter pulmonary blood flow. To produce ventilation, the mammalian lung must expand and contract, and so it is a highly compliant structure. Thus, because the capillaries are contained in the alveolar walls, alterations in the apparent gravitational force deform the lung and directly affect pulmonary blood flow both through lung deformation and through changes in the hydrostatic pressure distribution in the lung. High gravitational forces are encountered in the aviation environment, while gravity is absent in spaceflight. Diving subjects the lung to large increases in ambient pressure, while large reductions in pressure occur, often associated with alterations in oxygen level and airway pressure, in aviation. This article reviews the effects of alterations in both gravity and ambient pressure on the pulmonary circulation. © 2011 American Physiological Society.Compr Physiol1:319‐338, 2011.
Gas Exchange Under Altered Gravitational Stress
Authors: Prisk G. Kim
Published: January 2011

Efficient gas exchange in the lung depends on the matching of ventilation and perfusion. However, the human lung is a readily deformable structure and as a result gravitational stresses generate gradients in both ventilation and perfusion. Nevertheless, the lung is capable of withstanding considerable change in the applied gravitational load before pulmonary gas exchange becomes impaired. The postural changes that are part of the everyday existence for most bipedal species are well tolerated, as is the removal of gravity (weightlessness). Increases in the applied gravitational load result only in a large impairment in pulmonary gas exchange above approximately three times that on the ground, at which point the matching of ventilation to perfusion is so impaired that efficient gas exchange is no longer possible. Much of the tolerance of the lung to alterations in gravitation stress comes from the fact that ventilation and perfusion are inextricably coupled. Deformations in the lung that alter ventilation necessarily alter perfusion, thus maintaining a degree of matching and minimizing the disruption in ventilation to perfusion ratio and thus gas exchange. © 2011 American Physiological Society.Compr Physiol1:339‐355, 2011.
Distribution of Perfusion
Authors: Glenny Robb , Robertson H. Thomas
Published: January 2011

Local driving pressures and resistances within the pulmonary vascular tree determine the distribution of perfusion in the lung. Unlike other organs, these local determinants are significantly influenced by regional hydrostatic and alveolar pressures. Those effects on blood flow distribution are further magnified by the large vertical height of the human lung and the relatively low intravascular pressures in the pulmonary circulation. While the distribution of perfusion is largely due to passive determinants such as vascular geometry and hydrostatic pressures, active mechanisms such as vasoconstriction induced by local hypoxia can also redistribute blood flow. This chapter reviews the determinants of regional lung perfusion with a focus on vascular tree geometry, vertical gradients induced by gravity, the interactions between vascular and surrounding alveolar pressures, and hypoxic pulmonary vasoconstriction. While each of these determinants of perfusion distribution can be examined in isolation, the distribution of blood flow is dynamically determined and each component interacts with the others so that a change in one region of the lung influences the distribution of blood flow in other lung regions. © 2011 American Physiological Society.Compr Physiol1:245‐262, 2011.
Oncostatin M regulates neural precursor activity in the adult brain
Authors: Beatus Paul , Jhaveri Dhanisha J. , Walker Tara L. , Lucas Peter G. , Rietze Rodney L. , Cooper Helen M. , Morikawa Yoshihiro , Bartlett Perry F.
Published: January 2011

The regulation of neural precursor cell (NPC) activity is the major determinant of the rate of neuronal production in neurogenic regions of the adult brain. Here, we show that Oncostatin M (Osm) and its receptor, OsmRβ, are both expressed in the subventricular zone (SVZ) and that in contradistinction to leukemia inhibitory factor and ciliary neutrophic factor, Osm directly inhibits the proliferation of adult NPCs as measured by a decreased level of neurosphere formation in vitro. Similarly, intraventricular infusion of Osm dramatically decreases the pool of NPCs in both the SVZ and the hippocampus. In keeping with the inhibitory action of Osm, we reveal that mice lacking OsmRβ have substantially more NPCs in the SVZ, the hippocampus and the olfactory bulb, demonstrating that endogenous Osm signaling is important for NPC homeostasis. Finally, we show that Osm can also inhibit clonal growth of glioblastoma‐derived neurospheres, further supporting the close link between NPCs and tumor stem cells. © 2010 Wiley Periodicals, Inc. Develop Neurobiol 71: 619–633, 2011
Behavioral genetics in larval zebrafish: Learning from the young
Authors: Wolman Marc , Granato Michael
Published: January 2011

Deciphering the genetic code that determines how the vertebrate nervous system assembles into neural circuits that ultimately control behavior is a fascinating and challenging question in modern neurobiology. Because of the complexity of this problem, successful strategies require a simple yet focused experimental approach without limiting the scope of the discovery. Unbiased, large‐scale forward genetic screens in invertebrate organisms have yielded great insight into the genetic regulation of neural circuit assembly and function. For many reasons, this highly successful approach has been difficult to recapitulate in the behavioral neuroscience field's classic vertebrate model organisms—rodents. Here, we discuss how larval zebrafish provide a promising model system to which we can apply the design of invertebrate behavior‐based screens to reveal the genetic mechanisms critical for neural circuit assembly and function in vertebrates. © 2011 Wiley Periodicals, Inc. Develop Neurobiol 72: 366–372, 2012
Identification of adult mineralized tissue zebrafish mutants
Authors: Andreeva Viktoria , Connolly Michelle H. , Stewart‐Swift Caitlin , Fraher Daniel , Burt Jeffrey , Cardarelli Justin , Yelick Pamela C.
Published: January 2011

Zebrafish craniofacial, skeletal, and tooth development closely resembles that of higher vertebrates. Our goal is to identify viable adult zebrafish mutants that can be used as models for human mineralized craniofacial, dental, and skeletal system disorders. We used a large‐scale forward‐genetic chemical N‐ethyl‐nitroso‐urea mutagenesis screen to identify 17 early lethal homozygous recessive mutants with defects in craniofacial cartilage elements, and 7 adult homozygous recessive mutants with mineralized tissue phenotypes including craniofacial shape defects, fused sutures, dysmorphic or missing skeletal elements, scoliosis, and neural arch defects. One mutant displayed both an early lethal homozygous phenotype and an adult heterozygous phenotype. These results extend the utility of the zebrafish model beyond the embryo to study human bone and cartilage disorders. genesis 49:360–366, 2011. © 2011 Wiley‐Liss, Inc.
Crystal Structure, Spectroscopy and Crystal Field Analysis of Substituted 1,10‐Phenanthroline–Europium Complexes
Authors: Pan Zaifa , Jia Guohua , Duan Chang‐Kui , Wong Wai‐Yeung , Wong Wing‐Tak , Tanner Peter A.
Published: January 2011

Crystal structures and vibrational and electronic spectroscopic data are reported for europium(III) complexes with 5(or 4)‐R‐1,10‐phenanthroline (phen) ligands (R = chloro, methyl, nitro, amino). All complexes comprise a 10‐coordinate Eu3+ ion with three chelating nitrato anions and two bidentate phen ligands. The crystal structures are of three distinct types with space groups C2/c, P21/n and P. The room‐temperature emission spectra are dominated by the forced electric dipole 5D0 → 7F2 emission of Eu3+. The excitation spectra show that the triplet donor state of the nitro‐substituted complex has a lower energy than the other complexes and the lower luminescence quantum efficiency of this complex is rationalized. The emission spectra recorded at 10 K have been compared with those of the corresponding Eu3+‐doped yttrium complexes using different excitation lines as a criterion of sample purity. The spectrum of the unsubstituted phen complex is more clearly resolved than those of the other complexes and this has been attributed to disorder resulting in inhomogeneous broadening. A detailed crystal field analysis is given for the phen complex from the fitting of 24 crystal field energy levels. A comparison with other complexes has been made through derived second‐rank crystal field strengths. No simple relationships have been derived from comparisons of energy levels, spectral line positions, or second‐rank crystal field strengths with crystallographic data or Taft constants.
Vanadium(IV) and ‐(V) Complexes of Reduced Schiff Bases Derived from Aromatic o‐Hydroxyaldehydes and Tyrosine Derivatives
Authors: Correia Isabel , Marcão Susana , Koci Kamila , Tomaz Isabel , Adão Pedro , Kiss Tamás , Jakusch Tamás , Avecilla Fernando , Costa Pessoa João
Published: January 2011

The reduced Schiff bases of salicylaldehyde and pyridoxal (and o‐vaniline) with L‐tyrosine (Tyr) and D,L‐o‐tyrosine (o‐Tyr), designated as sal‐Tyr (1), sal‐o‐Tyr (2), pyr‐Tyr (3), pyr‐o‐Tyr (4), and o‐van‐L‐Tyr (5), as well as the oxidovanadium(IV) complex VO(sal‐o‐Tyr) (6) have been prepared. The compounds have been characterized in the solid state and in solution. The structure of 3 has been determined by X‐ray diffraction. Complexation of these ligands with vanadium in aqueous solution has been studied by pH potentiometry, UV/Vis, and circular dichroism (for the L‐Tyr derivatives), as well as by EPR for the VIVO systems and 51V NMR for the VVO2 systems. Stoichiometries and complex formation constants have been determined by pH potentiometry (25 °C, I = 0.2 M KCl) 1:1 complexes are formed in most systems with variable protonation states VOLH2 (only with 3 and 4), VOLH, VOL, and VOLH–1. Dinuclear species (VOL)2H and (VOL)2 were identified only in the case of 3. Spectroscopic data provided information about the most probable binding modes for each stoichiometry. The VIVO complexes formed with the o‐Tyr‐derived ligands are more stable than those with L‐Tyr, the more adequate coordination position of the phenolate in the o‐Tyr ligands shows a more significant stabilizing effect compared with 3 and 4.
Stereoselective Total Synthesis of (+)‐Nephrosteranic Acid and (+)‐Roccellaric Acid through Asymmetric Dihydroxylation and Johnson–Claisen Rearrangement
Authors: Fernandes Rodney A. , Chowdhury Asim K.
Published: January 2011

An efficient stereoselective total synthesis of (+)‐nephrosteranic acid and (+)‐roccellaric acid is presented. The synthetic strategy features the regioselective asymmetric dihydroxylation of the γ,δ‐olefinic bond of a α,β,γ,δ‐unsaturated ester and the Johnson–Claisen rearrangement as the key steps. The synthesis is achieved in 10 steps and 6.8 % (nephrosteranic acid) and 7.6 % (roccellaric acid) overall yield.
Depression and its correlates in older adults in Ukraine
Authors: Tintle Nathan , Bacon Branden , Kostyuchenko Stanislav , Gutkovich Zinoviy , Bromet Evelyn J.
Published: January 2011

Objective

Little is known about the epidemiology of late life depression in Eastern Europe. This study examined the 12‐month prevalence and correlates of DSM‐IV major depressive episode (MDE) in adults age 50 years and over in Ukraine. The correlates included demographic factors, mental health and alcohol history, physical conditions, and impairments in functioning.

Methods

A cross‐sectional survey was conducted in Ukraine using the Composite International Diagnostic Interview (CIDI‐3.0) as part of the World Health Organization–World Mental Health Survey Initiative. The sample included 1843 respondents age 50–91. Unadjusted and adjusted odds ratios were used to examine associations of the risk factors with 12‐month MDE in men and women separately.

Results

The 12‐month prevalence of MDE was 14.4% in women and 7.1% in men. In both sexes, history of MDE before age 50 and poor self‐assessed mental/physical health were significantly associated with MDE. Additionally, in men, living alone, 5+ physician visits, and role impairment, but not alcoholism, were associated with depression; in women, poverty, history of anxiety disorder, medical conditions, and cognitive and self‐care impairment were significant.

Conclusions

The 12‐month prevalence of late life MDE was substantially higher in Ukraine than in Western Europe and other developed countries. The risk factors, however, were similar to those found outside Ukraine. Depression is a recurrent condition, and history of depression was the strongest risk factor. Overall, the results show that older people in Ukraine constitute a high‐risk group for MDE and would therefore benefit from targeted interventions by primary care physicians. Copyright © 2011 John Wiley & Sons, Ltd.
99mTC‐octreotide scintigraphy and somatostatin receptor subtype expression in juvenile nasopharyngeal angiofibromas
Authors: Kukwa Wojciech , Andrysiak Renata , Kukwa Andrzej , Hubalewska‐Dydejczyk Alicja , Gronkiewicz Zuzanna , Wojtowicz Piotr , Krolicki Leszek , Wierzchowski Wojciech , Grochowski Tomasz , Czarnecka Anna M.
Published: January 2011

Background

The main goal of the study was the analysis of somatostatin receptor (SSTR) expression on juvenile nasopharyngeal angiofibroma (JNA) cells and a subsequent analysis of the utility of SST analog‐based scintigraphy in JNA diagnostics.

Methods

Nine JNA cases were analyzed. All tissue samples were analyzed for the expression of SSTRs. In 2 cases, scintigraphy was performed after the intravenous (IV) administration of an SST analog. MRI of the craniofacial region was subsequently performed.

Results

The SST analogues were accumulated in areas matching pathologic tissue in the nasopharynx. Immunohistochemical evaluation of the tissue samples proved the overexpression of SSTRs.

Conclusions

SSTRs are overexpressed on JNA cells. The SST analog99mTC‐octreotide is effectively bound to JNA cells. SST analogues might be used in the diagnostics and treatment of primary, recurrent, or residual JNA. © 2011 Wiley Periodicals, Inc. Head Neck, 2011
Hepatic Stellate Cells Regulate Immune Response by Way of Induction of Myeloid Suppressor Cells in Mice Δσ
Authors: Chou Hong-Shiue , Hsieh Ching-Chuan , Yang Horng-Ren , Wang Lianfu , Arakawa Yusuke , Brown Kathleen , Wu Qingyu , Lin Feng , Peters Marion , Fung John J. , Lu Lina , Qian Shiguang
Published: January 2011

Although organ transplants have been applied for decades, outcomes of somatic cell transplants remain disappointing, presumably due to lack of appropriate supporting stromal cells. Thus, cotransplantation with liver stromal cells, hepatic stellate cells (HSC), achieves long-term survival of islet allografts in mice by way of induction of effector T cell apoptosis and generation of regulatory T (Treg) cells. In this study we provide evidence both

in vitro

and

in vivo

that HSC can promote generation of myeloid-derived suppressor cells (MDSC). HSC-induced MDSC demonstrate potent immune inhibitory activity. Induction of MDSC is dependent on an intact interferon gamma signaling pathway in HSC and is mediated by soluble factors, suggesting that the specific tissue stromal cells, such as HSC, play a crucial role in regulating immune response by way of inflammation-induced generation of MDSC. Large amounts of MDSC can be propagated

in vitro

from bone marrow-derived myeloid precursor cells under the influence of HSC.

Conclusion:

Cotransplantation with

in vitro

generated MDSC can effectively protect islet allografts from host immune attack. Local delivery of potent immune suppressor cells for cell transplants holds great clinical application potential. (Hepatology 2011;)
Progression risk of columnar cell lesions of the breast diagnosed in core needle biopsies
Authors: Verschuur‐Maes Anoek H.J. , Witkamp Arjen J. , de Bruin Peter C. , van der Wall Elsken , van Diest Paul J.
Published: January 2011

Columnar cell lesions (CCLs) of the breast are recognized as putative precursor lesions of invasive carcinoma, but their management remains controversial. We therefore conducted a retrospective study on 311 CCLs, diagnosed in 4,164 14‐gauge core needle biopsies (CNB): 221 CCLs without atypia (CCL), 69 with atypia (CCL‐A), and 21 atypical ductal hyperplasias originating in CCL (ADH‐CCL). Two groups were identified: “immediate treatment” group undergoing excision within four months after the CNB diagnosis of CCL (N = 52) and the “wait‐and‐see” group followed up to 8 years (median 3.5 years, N = 259). In 7 of 31 women (22.5%, 1 CCL, 4 CCL‐A, 2 ADH‐CCL) who underwent immediate surgical excision and were initially biopsied for microcalcifications, ductal carcinoma in situ (DCIS) was present and in 2/31 women (6.5%, 1 CCL, 1 CCL‐A) invasive carcinoma. In 2/21 excisions (9.5%, 1 CCL, 1 CCL‐A) initially biopsied for a density, DCIS was present and invasive carcinoma in 5/21 excisions (23.8%, 2 CCL, 3 CCL‐A). In the wait‐and‐see group, 9/259 women (3.5%) developed invasive carcinoma, 6 ipsi, and 3 contralaterally. Progression risks of CCL‐A and ADH‐CCL were 18% and 22%,versus 2% for CCL without atypia (p < 0.001). In conclusion, CCL‐A or ADH‐CCL in a CNB were associated with a high risk of DCIS/invasive carcinoma in immediate surgical excision biopsies. The 8‐years progression risks for CCL‐A and ADH‐CCL were around 20%. This illustrates that an atypical CCL in a CNB may signal the presence of concurrent lesions or development of advanced lesions in future and may justify (“mini”) surgical excision.
Head neck squamous cell carcinoma c‐Met+ cells display cancer stem cell properties and are responsible for cisplatin‐resistance and metastasis
Authors: Sun Shuyang , Wang Zuolin
Published: January 2011

c‐Met, the tyrosine kinase receptor for hepatocyte growth factor, is overexpressed in a variety of tumors in which it plays a central role in malignant transformation. Although c‐Met has also been determined to be a critical signaling molecule in normal stem cell function, the potential role of c‐Met as a single marker for cancer stem cells (CSCs) has not been previously examined. In our study, we reported that human head neck squamous cell carcinoma (HNSCC) cells expressing c‐Met were capable of self‐renewal and of generating tumors that recapitulate the heterogeneity of the parental tumors, and isolation of HNSCC cells using a second marker CD44 could further enhance upon the in‐vivo tumorigenicity. We also reported that c‐Met+ HNSCC cells could readily make spherical colonies in nonadherent culture conditions, in contrast, c‐Met− population did not; these spherical colonies could be passaged multiple times without loss of colony‐forming capability. Furthermore, we showed that c‐Met+ HNSCC cells have increased expression of self‐renewal pathways are spared by cisplatin treatment and are responsible for mediating metastasis. These results indicated that c‐Met could serve as a novel marker for CSCs at least in HNSCC, and the highly chemoresistant and metastatic capabilities of c‐Met+ HNSCC population make them an important cell type to better define and understand their function.
Vegetables and fruits consumption and risk of esophageal and gastric cancer subtypes in the Netherlands Cohort Study
Authors: Steevens Jessie , Schouten Leo J. , Goldbohm R. Alexandra , van den Brandt Piet A.
Published: January 2011

Prospective epidemiologic data on vegetables and fruits consumption and risk of subtypes of esophageal and gastric cancer are sparse. We studied the association between vegetables and fruits consumption and risk of esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), gastric cardia adenocarcinoma (GCA) and gastric noncardia adenocarcinoma (GNCA) in the Netherlands Cohort Study. In 1986, 120,852 Dutch men and women aged 55–69 filled out a questionnaire on diet and other cancer risk factors. After 16.3 years of follow‐up, 101 ESCC, 144 EAC, 156 GCA, 460 GNCA cases and 4,035 subcohort members were available for case–cohort analysis using Cox proportional hazards models. Multivariable adjusted incidence rate ratios (RRs) were generally below unity. Total vegetable consumption was nonsignificantly inversely associated with EAC and ESCC risk, but not with GCA and GNCA risk. Significant inverse associations were observed for raw vegetables and EAC risk [RR per 25 g/day: 0.81, 95% confidence interval (CI) 0.68–0.98], and Brassica vegetables and GCA risk (RR per 25 g/day: 0.72, 95% CI 0.54–0.95). Total fruit consumption was associated with a nonsignificantly decreased EAC risk. Citrus fruits were inversely associated with EAC and GCA risk (RRs for highestvs.lowest intake: 0.55, 95% CI 0.31–0.98 and 0.38, 95% CI 0.21–0.69, respectively). Specifically for current smokers, vegetables and possibly also fruits intake was inversely associated with ESCC and EAC risk. Consumption of (specific groups of) vegetables and fruits may protect against subtypes of esophageal and gastric cancer.
Elevated risk of colorectal adenoma with Helicobacter pylori‐related chronic gastritis: A population‐based case‐control study
Authors: Inoue Izumi , Mukoubayashi Chizu , Yoshimura Noriko , Niwa Tohru , Deguchi Hisanobu , Watanabe Mika , Enomoto Shotaro , Maekita Takao , Ueda Kazuki , Iguchi Mikitaka , Yanaoka Kimihiko , Tamai Hideyuki , Arii Kenji , Oka Masashi , Fujishiro Mitsuhiro , Takeshita Tatsuya , Iwane Masataka , Mohara Osamu , Ichinose Masao
Published: January 2011

This study investigated correlations between Helicobacter pylori infection or chronic atrophic gastritis (CAG) and risk of colorectal adenoma in a population‐based case‐control study. Subjects comprised asymptomatic, middle‐aged, male Japanese factory workers who participated in an annual health check‐up program, including cancer screening with colonoscopy. We selected 239 colorectal adenoma cases based on histological evaluation and 239 age‐matched adenoma‐free controls, and evaluated colorectal adenoma risk according to stage of H. pylori‐related chronic gastritis as determined by serum tests for H. pylori antibody titer and pepsinogen. Subjects with colorectal adenoma were more likely to be smokers and have hypercholesterolemia. H. pylori infection was a risk factor for adenoma as a whole (crude odds ratio [OR]: 2.26, 95% confidence interval [CI]: 1.44–3.55). Analysis of distal adenoma cases showed that adenoma risk was significantly increased in the presence of H. pylori infection, but there was no further increase in risk with CAG. In contrast, proximal adenoma risk increased stepwise with the presence and progression of H. pylori‐related chronic gastritis and showed a maximal and significant increase with CAG (crude OR: 4.51, 95% CI: 1.43–14.2). Subjects with more extensive and severe gastritis showed still higher risk not only for proximal but also for distal adenoma. H. pylori‐related chronic gastritis is likely to be involved in the development of colorectal neoplasms, and its progression appears to increase the risk, particularly for proximal adenomas. Knowing the H. pylori‐related chronic gastritis stage will probably be useful for evaluation of risk for colorectal neoplasia.
Inhibition of ovarian cancer by RGD‐P125A‐endostatin‐Fc fusion proteins
Authors: Jing Yawu , Lu Huarui , Wu Kailang , Subramanian Indira V. , Ramakrishnan S.
Published: January 2011

Previous studies have shown that a single point mutation in endostatin at position 125 (P125A) can improve the biological activity of endostatin. Addition of an integrin‐targeting moiety, R‐G‐D, resulted in better localization to tumor vasculature and improved the antiangiogenic activity of endostatin. Because endostatin has relatively shorter serum half‐life, frequent dosing was required for inhibiting tumor growth. In our study, we have genetically fused RGD‐P125A‐endostatin to Fc of IgG4 isotype and evaluated its antiangiogenic and antitumor effects in athymic mice. Two genetic constructs were made, RGD‐P125A‐endostatin‐Fc (RE‐Fc) and P125A‐endostatin‐RGD‐Fc (ER‐Fc). Both constructs were cloned and expressed in mammalian cells. Purified fusion proteins inhibited endothelial cell migration and proliferation better than yeast‐derived P125A‐endostatin. Both RE‐Fc and ER‐Fc inhibited ovarian cancer growth and were found to be as effective as Bevacizumab treatment. Fusion protein showed marked increased half‐life. Combination treatment with Bevacizumab and ER‐Fc showed additive inhibition of ovarian cancer growth. These studies demonstrate that genetic fusion with human IgG4‐Fc increases the half‐life of P125A‐endostatin and can be used along with Bevacizumab to improve antiangiogenic and antitumor activities.
Characterization of cytolytic neutrophil activation in vitro by amorphous hydrated calcium phosphate as a model of biomaterial inflammation
Authors: Edwards Felicity C. , Taheri Amir , Dann Sophie C. , Dye Julian F.
Published: January 2011

Calcium ions are utilized in biomolecular biomaterial design for osteomimetic scaffolds and as divalent cross‐linking agents, typically for gelation of alginates, stabilisation of protein structure (e.g., fibrinogen) and enzyme activation (e.g., thrombin). Biological interactions with defined calcium phosphates (e.g., hydroxyapatite) are exploited for osteogenesis, although crystalline calcium phosphates (e.g., calcium pyrophosphate) stimulate inflammation. We found that the calcium concentration used in the manufacture of prototype dermal scaffolds made from fibrin/alginate composite was related to the inflammatory infiltration during in vivo integration. In investigating a cause for this inflammatory response, we have identified and characterized a cytolytic inflammatory effect of amorphous calcium phosphate (CaP) formed in physiological solutions, relevant to biomaterial biocompatibility. Isolated human neutrophils (Nφ) were incubated in phosphate‐buffered saline with CaCl2 ranging 2.5–20 mM total calcium. Nφ activation was assessed by morphology and integrin‐β2 (CD18a) expression. Mediator release (Nφ‐elastase, IL‐8, and TNFα) was measured from both Nφ and whole blood cultures plus CaCl2. CaP exposure increased CD18a expression over 1 h (maximal at 10 mM calcium/ phosphate) with concurrent phagocytosis, cytolysis, and Nφ‐elastase release. CaCl2 induced expression of IL‐8 and TNFα in whole blood cultures. These results suggest that CaP formed from the resorption of calcium‐containing biomaterials could induce inflammation and accelerate biomaterial degradation, driving further CaP release. This demonstrates a novel mechanism for biomaterial‐induced inflammation. The in vitro system described could aid preclinical evaluation of novel biomaterial inflammatory potential. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2011.