bluuebunny/crossref_metadata_2025_split huggingface dataset:
Favorable response to doxorubicin combination chemotherapy does not yield good clinical outcome in patients with metastatic breast cancer with triple-negative phenotype
Authors: Yi Seong Yoon , Ahn Jin Seok , Uhm Ji Eun , Lim Do Hyoung , Ji Sang Hoon , Jun Hyun Jung , Kim Kyoung Ha , Chang Myung Hee , Park Min Jae , Cho Eun Yoon , La Choi Yoon , Park Yeon Hee , Im Young-Hyuck 
Published: October 2010

Abstract

Background
We analyzed the responses to first line treatment and clinical outcomes of metastatic breast cancer patients treated with palliative doxorubicin/cyclophosphamide (AC) according to molecular cancer subtype.

Methods
A retrospective analysis was performed for 110 metastatic breast cancer patients selected on the basis of palliative AC treatment and the availability of immunohistochemical data for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER-2/neu) status.

Results
Of the 110 patients analyzed, 71 (64.5%) were hormone receptor positive (HR+), 14 (12.7%) were HER2+, and 25 (22.7%) were triple negative (TN). There were no differences in age, stage at diagnosis, total number of cycles of palliative chemotherapy, incidence of visceral metastasis, and metastatic sites with the exception of liver among breast cancer subtypes. The overall response rates to AC were 55.9% for the HR+ subgroup, 42.9% for the HER2+ subgroup, and 56.5% for the TN subgroup. The progression-free survival (PFS) in patients with HER2+ and TN were significantly shorter than in the HR+ (median PFS, 9.1 vs 8.1 vs 11.5 months, respectively; p = 0.0002). The overall survival (OS) was 25.4 months in the TN subgroup and 27.3 months in HER2+ subgroup. The median OS for these two groups was significantly shorter than for patients in the HR+ subgroup (median, 38.5 months; 95% CI, 30.1-46.9 months; p < 0.0001).

Conclusions
The response to palliative AC chemotherapy did not differ among breast cancer subtypes. Despite chemosensitivity for palliative AC, the TN subtype has a shorter overall survival than non-TN subtypes. Innovative treatment strategies should be developed to slow the course of disease.
Relating the shape of protein binding sites to binding affinity profiles: is there an association?
Authors: Simon Zoltán , Vigh-Smeller Margit , Peragovics Ágnes , Csukly Gábor , Zahoránszky-Kőhalmi Gergely , Rauscher Anna Á , Jelinek Balázs , Hári Péter , Bitter István , Málnási-Csizmadia András , Czobor Pál 
Published: October 2010

Abstract

Background
Various pattern-based methods exist that use in vitro or in silico affinity profiles for classification and functional examination of proteins. Nevertheless, the connection between the protein affinity profiles and the structural characteristics of the binding sites is still unclear. Our aim was to investigate the association between virtual drug screening results (calculated binding free energy values) and the geometry of protein binding sites. Molecular Affinity Fingerprints (MAFs) were determined for 154 proteins based on their molecular docking energy results for 1,255 FDA-approved drugs. Protein binding site geometries were characterized by 420 PocketPicker descriptors. The basic underlying component structure of MAFs and binding site geometries, respectively, were examined by principal component analysis; association between principal components extracted from these two sets of variables was then investigated by canonical correlation and redundancy analyses.

Results
PCA analysis of the MAF variables provided 30 factors which explained 71.4% of the total variance of the energy values while 13 factors were obtained from the PocketPicker descriptors which cumulatively explained 94.1% of the total variance. Canonical correlation analysis resulted in 3 statistically significant canonical factor pairs with correlation values of 0.87, 0.84 and 0.77, respectively. Redundancy analysis indicated that PocketPicker descriptor factors explain 6.9% of the variance of the MAF factor set while MAF factors explain 15.9% of the total variance of PocketPicker descriptor factors. Based on the salient structures of the factor pairs, we identified a clear-cut association between the shape and bulkiness of the drug molecules and the protein binding site descriptors.

Conclusions
This is the first study to investigate complex multivariate associations between affinity profiles and the geometric properties of protein binding sites. We found that, except for few specific cases, the shapes of the binding pockets have relatively low weights in the determination of the affinity profiles of proteins. Since the MAF profile is closely related to the target specificity of ligand binding sites we can conclude that the shape of the binding site is not a pivotal factor in selecting drug targets. Nonetheless, based on strong specific associations between certain MAF profiles and specific geometric descriptors we identified, the shapes of the binding sites do have a crucial role in virtual drug design for certain drug categories, including morphine derivatives, benzodiazepines, barbiturates and antihistamines.
The frequency of CD25+CD4+ and FOXP3+ regulatory T cells in ectopic endometrium and ectopic decidua
Authors: Basta Pawel , Majka Marcin , Jozwicki Wojciech , Lukaszewska Ewelina , Knafel Anna , Grabiec Marek , Stasienko Elzbieta , Wicherek Lukasz 
Published: October 2010

Abstract

Background
The presence of regulatory T (Treg) cells in human endometrium is crucial for maintaining immunological homeostasis within the uterus. For this study we decided to evaluate the subpopulations of Treg cells in conditions where a disturbance in the immunological equilibrium in ectopic endometrium and decidua has been observed, such as in cases of ovarian endometriosis (involving local immune cell suppression) and ectopic pregnancy (involving an increase in local immune system activity). We then compared these findings to what we observed in the normal eutopic endometrium of women during the secretory phase of the menstrual cycle (with immune cells under individual control).

Methods
The endometrium tissue samples evaluated in our study were obtained from 47 women during one of two kinds of laparoscopic procedures. 16 of the women underwent laparoscopies due to Fallopian tube pregnancies (EP), and 16 due to ovarian endometrioma, while 15 women made up a control group. The presence of regulatory T cells in these tissue samples was evaluated by FACS.

Results
In our study, the percentages of FOXP3+ cells within the subpopulation of CD4+ T lymphocytes found in the decidua of the patients treated for Fallopian tube pregnancies were statistically significantly lower than both those observed in the ovarian endometriosis tissue samples and those found in the secretory eutopic endometrium samples of the control group.

Conclusion
The disturbance in the immunological equilibrium observed in ectopic endometrium and decidua would seem to be related to the alteration in the Treg cell population that occurs in these ectopic tissues.
Increased matrix metalloproteinase activation in esophageal squamous cell carcinoma
Authors: Mukherjee Sumana , Roth Mark J , Dawsey Sanford M , Yan Wusheng , Rodriguez-Canales Jaime , Erickson Heidi S , Hu Nan , Goldstein Alisa M , Taylor Philip R , Richardson Annely M , Tangrea Michael A , Chuaqui Rodrigo F , Emmert-Buck Michael R 
Published: October 2010

Abstract

Background
Esophageal squamous cell carcinomas (ESCC) are usually asymptomatic and go undetected until they are incurable. Cytological screening is one strategy to detect ESCC at an early stage and has shown promise in previous studies, although improvement in sensitivity and specificity are needed. Proteases modulate cancer progression by facilitating tumor invasion and metastasis. In the current study, matrix metalloproteinases (MMPs) were studied in a search for new early detection markers for ESCC.

Methods
Protein expression levels of MMPs were measured using zymography in 24 cases of paired normal esophagus and ESCC, and in the tumor-associated stroma and tumor epithelium in one sample after laser capture microdissection (LCM). MMP-3 and MMP-10 transcripts in both the epithelium and stroma in five cases were further analyzed by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR).

Results
Gelatin zymography showed bands corresponding in size to MMP-2, MMP-3, MMP-9, and MMP-10 enzymes in each of the 24 cancer cases. MMP levels tended to be higher in tumors than paired normal tissue; however, only the 45 kDa band that corresponds to the activated form of MMP-3 and MMP-10 was strongly expressed in all 24 tumors with little or no expression in the paired normal foci. LCM-based analysis showed the 45 kDA band to be present in both the stromal and epithelial components of the tumor microenvironment, and that MMP-3 and MMP-10 mRNA levels were higher in tumors than paired normal tissues for each compartment.

Conclusions
Increased levels of MMPs occur in ESCC suggesting their up-regulation is important in esophageal tumorigenesis. The up-regulated gene products have the potential to serve as early detection markers in the clinic.
Folk medicine used to heal malaria in Calabria (southern Italy)
Authors: Tagarelli Giuseppe , Tagarelli Antonio , Piro Anna 
Published: October 2010

AbstractIn Italy, malaria was an endemic disease that was eradicated by the mid-20th century. This paper evaluates the prophylactic and therapeutic remedies used by folk medicine to cure malaria in Calabria (southern Italy).The data has been collected by analysing works of physicians, ethnographers, folklorists and specialists of the study of Calabrian history between the end of the 19th century and the 20th century. The data collected have allowed us to describe the most common cures used by the Calabrian people to treat malaria and the most evident symptoms of this disease, such as intermittent fever, hepato-spleenomegaly, asthenia and dropsy. This approach uncovered a heterogeneous corpus of empirical, magical and religious remedies, which the authors have investigated as evidences of past "expert medicine" and to verify their real effectiveness in the treatment of malaria.
A novel mutation of the ACADM gene (c.145C>G) associated with the common c.985A>G mutation on the other ACADM allele causes mild MCAD deficiency: a case report
Authors: Dessein Anne-Frédérique , Fontaine Monique , Andresen Brage S , Gregersen Niels , Brivet Michèle , Rabier Daniel , Napuri-Gouel Silvia , Dobbelaere Dries , Mention-Mulliez Karine , Martin-Ponthieu Annie , Briand Gilbert , Millington David S , Vianey-Saban Christine , Wanders Ronald JA , Vamecq Joseph 
Published: October 2010

Abstract
A female patient, with normal familial history, developed at the age of 30 months an episode of diarrhoea, vomiting and lethargy which resolved spontaneously. At the age of 3 years, the patient re-iterated vomiting, was sub-febrile and hypoglycemic, fell into coma, developed seizures and sequels involving right hemi-body. Urinary excretion of hexanoylglycine and suberylglycine was low during this metabolic decompensation. A study of pre- and post-prandial blood glucose and ketones over a period of 24 hours showed a normal glycaemic cycle but a failure to form ketones after 12 hours fasting, suggesting a mitochondrial β-oxidation defect. Total blood carnitine was lowered with unesterified carnitine being half of the lowest control value. A diagnosis of mild MCAD deficiency (MCADD) was based on rates of 1-14C-octanoate and 9, 10-3H-myristate oxidation and of octanoyl-CoA dehydrogenase being reduced to 25% of control values. Other mitochondrial fatty acid oxidation proteins were functionally normal. De novo acylcarnitine synthesis in whole blood samples incubated with deuterated palmitate was also typical of MCADD. Genetic studies showed that the patient was compound heterozygous with a sequence variation in both of the two ACADM alleles; one had the common c.985A>G mutation and the other had a novel c.145C>G mutation. This is the first report for the ACADM gene c.145C>G mutation: it is located in exon 3 and causes a replacement of glutamine to glutamate at position 24 of the mature protein (Q24E). Associated with heterozygosity for c.985A>G mutation, this mutation is responsible for a mild MCADD phenotype along with a clinical story corroborating the emerging literature view that patients with genotypes representing mild MCADD (high residual enzyme activity and low urinary levels of glycine conjugates), similar to some of the mild MCADDs detected by MS/MS newborn screening, may be at risk for disease presentation.
Variations in the length of stay of intensive care unit nonsurvivors in three scandinavian countries
Authors: Strand Kristian , Walther Sten M , Reinikainen Matti , Ala-Kokko Tero , Nolin Thomas , Martner Jan , Mussalo Petteri , Søreide Eldar , Flaatten Hans K 
Published: October 2010

Abstract
Introduction
The length of stay (LOS) in intensive care unit (ICU) nonsurvivors is not often reported, but represents an important indicator of the use of resources. LOS in ICU nonsurvivors may also be a marker of cultural and organizational differences between units. In this study based on the national intensive care registries in Finland, Sweden, and Norway, we aimed to report intensive care mortality and to document resource use as measured by LOS in ICU nonsurvivors.

Methods
Registry data from 53,305 ICU patients in 2006 were merged into a single database. ICU nonsurvivors were analyzed with regard to LOS within subgroups by univariate and multivariate analysis (Cox proportional hazards regression).

Results
Vital status at ICU discharge was available for 52,255 patients. Overall ICU mortality was 9.1%. Median LOS of the nonsurvivors was 1.3 days in Finland and Sweden, and 1.9 days in Norway. The shortest LOS of the nonsurvivors was found in patients older than 80 years, emergency medical admissions, and the patients with the highest severity of illness. Multivariate analysis confirmed the longer LOS in Norway when corrected for age group, admission category, sex, and type of hospital. LOS in nonsurvivors was found to be inversely related to the severity of illness, as measured by APACHE II and SAPS II.

Conclusions
Despite cultural, religious, and educational similarities, significant variations occur in the LOS of ICU nonsurvivors among Finland, Norway, and Sweden. Overall, ICU mortality is low in the Scandinavian countries.
Randomized Phase III Study of Panitumumab With Fluorouracil, Leucovorin, and Irinotecan (FOLFIRI) Compared With FOLFIRI Alone As Second-Line Treatment in Patients With Metastatic Colorectal Cancer
Authors: Peeters Marc , Price Timothy Jay , Cervantes Andrés , Sobrero Alberto F. , Ducreux Michel , Hotko Yevhen , André Thierry , Chan Emily , Lordick Florian , Punt Cornelis J.A. , Strickland Andrew H. , Wilson Gregory , Ciuleanu Tudor-Eliade , Roman Laslo , Van Cutsem Eric , Tzekova Valentina , Collins Simon , Oliner Kelly S. , Rong Alan , Gansert Jennifer 
Published: October 2010

Purpose Panitumumab is a fully human anti–epidermal growth factor receptor (EGFR) monoclonal antibody that improves progression-free survival (PFS) in chemotherapy-refractory metastatic colorectal cancer (mCRC). This trial evaluated the efficacy and safety of panitumumab plus fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone after failure of initial treatment for mCRC by tumor KRAS status. Patients and Methods Patients with mCRC, one prior chemotherapy regimen for mCRC, Eastern Cooperative Oncology Group performance status 0 to 2, and available tumor tissue for biomarker testing were randomly assigned 1:1 to panitumumab 6.0 mg/kg plus FOLFIRI versus FOLFIRI every 2 weeks. The coprimary end points of PFS and overall survival (OS) were independently tested and prospectively analyzed by KRAS status. Results From June 2006 to March 2008, 1,186 patients were randomly assigned 1:1 and received treatment. KRAS status was available for 91% of patients: 597 (55%) with wild-type (WT) KRAS tumors, and 486 (45%) with mutant (MT) KRAS tumors. In the WT KRAS subpopulation, when panitumumab was added to chemotherapy, a significant improvement in PFS was observed (hazard ratio [HR] = 0.73; 95% CI, 0.59 to 0.90; P = .004); median PFS was 5.9 months for panitumumab-FOLFIRI versus 3.9 months for FOLFIRI. A nonsignificant trend toward increased OS was observed; median OS was 14.5 months versus 12.5 months, respectively (HR = 0.85, 95% CI, 0.70 to 1.04; P = .12); response rate was improved to 35% versus 10% with the addition of panitumumab. In patients with MT KRAS, there was no difference in efficacy. Adverse event rates were generally comparable across arms with the exception of known toxicities associated with anti-EGFR therapy. Conclusion Panitumumab plus FOLFIRI significantly improved PFS and is well-tolerated as second-line treatment in patients with WT KRAS mCRC.
Phase II Selection Design Trial of Concurrent Chemotherapy and Cetuximab Versus Chemotherapy Followed by Cetuximab in Advanced-Stage Non–Small-Cell Lung Cancer: Southwest Oncology Group Study S0342
Authors: Herbst Roy S. , Kelly Karen , Chansky Kari , Mack Philip C. , Franklin Wilbur A. , Hirsch Fred R. , Atkins James N. , Dakhil Shaker R. , Albain Kathy S. , Kim Edward S. , Redman Mary , Crowley John J. , Gandara David R. 
Published: October 2010

Purpose Randomized clinical trials failed to show a survival benefit for epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors plus concurrent chemotherapy in patients with metastatic non–small-cell lung cancer (NSCLC), with preclinical data suggesting potential negative interactions. In contrast, pilot trials of the EGFR-targeted antibody, cetuximab, plus chemotherapy suggested enhanced antitumor activity. This randomized phase II trial was designed to select a cetuximab plus chemotherapy regimen for phase III evaluation. Patients and Methods Treatment-naive patients with advanced-stage NSCLC were randomly assigned to receive paclitaxel (225 mg/m2) and carboplatin (area under the curve, 6) every 3 weeks plus concurrent cetuximab (400 mg/m2 loading dose followed by 250 mg/m2 weekly) for four cycles followed by maintenance cetuximab or sequential paclitaxel-carboplatin for four cycles followed by cetuximab. Results Of 242 patients enrolled, 224 were eligible and assessable for response (106 and 118 patients in the concurrent and sequential arms, respectively). With a median follow-up time of 32 months, the median overall survival was 10.9 months (95% CI, 9.2 to 13.0 months) for patients receiving concurrent therapy and 10.7 months (95% CI, 8.5 to 12.8 months) for patients receiving sequential therapy (P = .57); 1-year survival rates were 45% (95% CI, 36% to 54%) and 44% (95% CI, 35% to 53%), respectively. Response rates and progression-free survival times were similar in both arms, as was grade 3 rash, whereas sensory neuropathy was higher in the concurrent arm (15% v 5% in the sequential arm; P = .036). Conclusion Although both regimens met the efficacy criterion for continued evaluation, the concurrent regimen of paclitaxel/carboplatin plus cetuximab was chosen.
Immunologic Escape After Prolonged Progression-Free Survival With Epidermal Growth Factor Receptor Variant III Peptide Vaccination in Patients With Newly Diagnosed Glioblastoma
Authors: Sampson John H. , Heimberger Amy B. , Archer Gary E. , Aldape Kenneth D. , Friedman Allan H. , Friedman Henry S. , Gilbert Mark R. , Herndon James E. , McLendon Roger E. , Mitchell Duane A. , Reardon David A. , Sawaya Raymond , Schmittling Robert J. , Shi Weiming , Vredenburgh James J. , Bigner Darell D. 
Published: October 2010

Purpose Immunologic targeting of tumor-specific gene mutations may allow precise eradication of neoplastic cells without toxicity. Epidermal growth factor receptor variant III (EGFRvIII) is a constitutively activated and immunogenic mutation not expressed in normal tissues but widely expressed in glioblastoma multiforme (GBM) and other neoplasms. Patients and Methods A phase II, multicenter trial was undertaken to assess the immunogenicity of an EGFRvIII-targeted peptide vaccine and to estimate the progression-free survival (PFS) and overall survival (OS) of vaccinated patients with newly diagnosed EGFRvIII-expressing GBM with minimal residual disease. Intradermal vaccinations were given until toxicity or tumor progression was observed. Sample size was calculated to differentiate between PFS rates of 20% and 40% 6 months after vaccination. Results There were no symptomatic autoimmune reactions. The 6-month PFS rate after vaccination was 67% (95% CI, 40% to 83%) and after diagnosis was 94% (95% CI, 67% to 99%; n = 18). The median OS was 26.0 months (95% CI, 21.0 to 47.7 months). After adjustment for age and Karnofsky performance status, the OS of vaccinated patients was greater than that observed in a control group matched for eligibility criteria, prognostic factors, and temozolomide treatment (hazard ratio, 5.3; P = .0013; n = 17). The development of specific antibody (P = .025) or delayed-type hypersensitivity (P = .03) responses to EGFRvIII had a significant effect on OS. At recurrence, 82% (95% CI, 48% to 97%) of patients had lost EGFRvIII expression (P < .001). Conclusion EGFRvIII-targeted vaccination in patients with GBM warrants investigation in a phase III, randomized trial.
Atomic Radii for Depicting Atoms in a Molecule II: The Effective Atomic Radius and van der Waals Radius from 1H to 54Xe
Authors: Tatewaki Hiroshi , Hatano Yasuyo , Naka Takatoshi , Noro Takeshi , Yamamoto Shigeyoshi 
Published: October 2010

Abstract
We consider the effective atomic radius (rear), defined as the distance from the nucleus at which the magnitude of the electric field is that in He at one half of the equilibrium bond length of He2, for atoms from H to Xe. The value of rear accurately reflects the electronic configuration; for example, the effective radius shortens smoothly from B 2s22p1 to Ne 2s22p6, in contrast to the van der Waals radius (rvdW) which behaves irregularly with atomic number from B to Ne. The valence radii (rval) are also defined and discussed. Values of rear and rval are used to depict the electron charge distribution of the homonuclear diatomic molecules of groups 15, 18, and transition-metal atoms, and provide insight into the characteristics of these molecules.
Bright White Upconversion Luminescence in β-NaGd0.794Yb0.20Ho0.001Tm0.005F4 Nanoparticles
Authors: De Gejihu , Yu Menggenqilavuqi , Bao Siqin 
Published: October 2010

Abstract
β-NaGd0.794Yb0.20Ho0.001Tm0.005F4 nanoparticles were synthesized through a simple hydrothermal method. The nanoparticles crystallized well and exhibited nearly hexagonal morphology and ellipsoidal spheres, as characterized by X-ray powder diffraction and transmission electron microscopy. The β-NaGd0.794Yb0.20Ho0.001Tm0.005F4 nanoparticles have an average size of about 23 nm. Room-temperature bright white upconversion luminescence in β-NaGd0.794Yb0.20Ho0.001Tm0.005F4 nanoparticles was obtained under single-wavelength diode laser excitation of 980 nm.
Synthesis and Optoelectronic Properties of Completely Carbazole-substituted Double-decker-shaped Silsesquioxane
Authors: Kohri Michinari , Matsui Jun , Watanabe Akira , Miyashita Tokuji 
Published: October 2010

Abstract
An organic–inorganic hybrid amorphous molecular material; carbazole-substituted double-decker-shaped silsesquioxane (DDSQ-4Cz) was synthesized, and an organic light-emitting diode was fabricated using the spin-coated DDSQ-4Cz film as a hole transport layer.
Solution-phase Assembly of a Rhodium Complex via Specific Hydrogen Bonding between Barbituric Acid and Triaminopyrimidine Moieties
Authors: Kondo Masataka , Kochi Takuya , Sato Mitsuo , Kitajima Aki , Kakiuchi Fumitoshi 
Published: October 2010

Abstract
Solution-phase assembly of a Rh complex using specific hydrogen bonding between BA and TAP moieties was achieved by tuning the substituent on TAP to control the solubility of the assembly.