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  1. 1
    دورية أكاديمية

    المساهمون: Terracciano, Rossana, Carcamo-Bahena, Yareli, Brian Butler, E., Demarchi, Danilo, Grattoni, Alessandro, Filgueira, Carly S.

    الوصف: Biofouling is the unwanted adsorption of cells, proteins, or intracellular and extracellular biomolecules that can spontaneously occur on the surface of metal nanocomplexes. It represents a major issue in bioinorganic chemistry because it leads to the creation of a protein corona, which can destabilize a colloidal solution and result in undesired macrophage-driven clearance, consequently causing failed delivery of a targeted drug cargo. Hyaluronic acid (HA) is a bioactive, natural mucopolysaccharide with excellent antifouling properties, arising from its hydrophilic and polyanionic characteristics in physiological environments which prevent opsonization. In this study, hyaluronate-thiol (HA-SH) (MW 10 kDa) was used to surface-passivate gold nanoparticles (GNPs) synthesized using a citrate reduction method. HA functionalized GNP complexes (HA-GNPs) were characterized using absorption spectroscopy, scanning electron microscopy, zeta potential, and dynamic light scattering. GNP cellular uptake and potential dose-dependent cytotoxic effects due to treatment were evaluated in vitro in HeLa cells using inductively coupled plasma—optical emission spectrometry (ICP-OES) and trypan blue and MTT assays. Further, we quantified the in vivo biodistribution of intratumorally injected HA functionalized GNPs in Lewis Lung carcinoma (LLC) solid tumors grown on the flank of C57BL/6 mice and compared localization and retention with nascent particles. Our results reveal that HA-GNPs show overall greater peritumoral distribution (** p < 0.005, 3 days post-intratumoral injection) than citrate-GNPs with reduced biodistribution in off-target organs. This property represents an advantageous step forward in localized delivery of metal nano-complexes to the infiltrative region of a tumor, which may improve the application of nanomedicine in the diagnosis and treatment of cancer.

    وصف الملف: ELETTRONICO

    العلاقة: info:eu-repo/semantics/altIdentifier/wos/WOS:000725800200001; volume:9; issue:11; firstpage:1561; numberofpages:19; journal:BIOMEDICINES; http://hdl.handle.net/11583/2935604Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85118335041; https://www.mdpi.com/2227-9059/9/11/1561Test

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    المصدر: Journal of Clinical Neuroscience. 85:115-121

    الوصف: Grade 3 gliomas are aggressive primary brain tumors. Promoter methylation of methyl guanine methyl transferase (MGMT) has been associated with a favorable prognosis in patients with glioblastoma, but the impact of MGMT promoter methylation in patients with grade 3 gliomas is less clear. The purpose of the present study was to evaluate the utilization of MGMT testing in patients with Grade 3 glioma, as well its prognostic and predictive value.The National Cancer Database (NCDB) was queried (2004-2016) for patients with newly diagnosed grade 3 glioma without 1p19q codeletion. Statistics included Kaplan-Meier overall survival (OS) analysis, along with Cox proportional hazards modeling.Of 20,488 total patients, 1,209 (5.0%) had MGMT testing. Of these patients, 561 (46.4%) were MGMT methylated (mMGMT), and 648 (53.6%) were MGMT unmethylated (uMGMT). mMGMT patients experienced greater median overall survival (OS) than both uMGMT patients as well as patients with no MGMT status reported (p 0.05 for both). mMGMT was associated with improved OS for patients receiving adjuvant chemoradiation or adjuvant radiation, but not for patients receiving adjuvant chemotherapy or no adjuvant treatment.This is the largest study to date describing the utilization of and outcomes for mMGMT patients with grade 3 glioma. The present results demonstrate that mMGMT is a prognostic factor and possibly a predictive biomarker, and is currently under-utilized within the US. MGMT methylation status could be used to risk-stratify and select patients for treatment intensification.The present study is the largest of its kind to examine the prognostic and predictive impact of MGMT methylation (mMGMT) amongst patients with Grade 3 Glioma. The results suggest that mMGMT is prognostic, as amongst all patients, mMGMT was associated with improved overall survival. These results also suggest that mMGMT is predictive, as patients treated with adjuvant chemoradiation or adjuvant radiation therapy did have improved overall survival with mMGMT, though there was no difference in overall survival observes amongst patients receiving adjuvant chemotherapy or those patients receiving no adjuvant treatment. The study also found that only 5% of patients nationwide with Grade 3 Glioma are tested for MGMT.

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    المصدر: Journal of Clinical Neuroscience. 84:8-14

    الوصف: Primary spinal cord tumors are rare, particularly in the adult population, and national guidelines remain ambiguous with regard to management approaches. To address this knowledge gap, we evaluated management, outcomes, and prognostic factors of these neoplasms.The National Cancer Database was queried (2004-2016) for newly-diagnosed, histologically-confirmed WHO grades I-III astrocytomas and glioblastoma. Statistics included Kaplan-Meier overall survival (OS) analysis, along with Cox proportional hazards modeling.Of 1,033 subjects, 196 (19%) were pilocytic astrocytomas (PAs), 539 (52%) were grade II/III astrocytomas, and 298 (29%) were glioblastomas (GBMs). Respectively, 11%, 30%, and 27% did not undergo resection (biopsy only). RT was delivered to 27%, 54%, and 73%; chemotherapy was given to 5%, 21%, and 37%, respectively. The median OS was not reached for PAs, but was 101.2 months for grade II/III astrocytomas, and 23.9 months for GBMs (p 0.001). Neither chemotherapy nor RT (or dose thereof) was associated with increased OS for grade II/III astrocytomas (p 0.05 for all), though there was a trend toward improved OS with the use of chemotherapy for patients with GBM. Surgical resection was associated with improved OS for grade II/III astrocytomas and GBM (p 0.05). Independent prognostic factors for survival in this cohort included histologic classification and resection (compared to biopsy only) (p 0.05 for both).This study sheds light onto the management of these rare tumors; surgery was associated with OS benefit for patients with GBM and Grade II/III astrocytomas. Neither RT nor chemotherapy were associated with OS benefit. Although not implying causation, these data can be used to guide patient counseling and therapeutic approaches.

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    المصدر: Journal of Clinical Neuroscience. 76:154-160

    الوصف: Purpose Adult medulloblastoma is rare, and management is extrapolated from pediatric cases. This investigation evaluated the prognostic role of chemotherapy (and sequencing thereof), the degree of resection, and craniospinal irradiation (CSI) dose. Methods The National Cancer Database was queried for adult (age ≥18) medulloblastoma. Resection was coded as gross (GTR) or subtotal resection (STR) or biopsy only; concurrent chemoradiotherapy (CRT) was defined as receipt within 14 days of each other. Statistics included Kaplan-Meier overall survival (OS) analysis and Cox proportional hazards modeling. Results Of 1144 patients, 613 had coded surgical information; 242 (39%) did not undergo surgery, 277 (45%) underwent STR, and 94 (15%) had GTR. A total of 428 (37.4%) did not receive chemotherapy, 348 (30.4%) received sequential CRT, and 368 (32.2%) underwent concurrent CRT. Of the 711 patients with CSI dose information, 202 (28.4%) received 23–30 Gy CSI and 509 (71.6%) patients received 30–36 Gy. Median follow-up was 56.5 months. Extent of resection did not correlate with 10-year OS (74.2% biopsy only, 72.7% STR, 82.2% GTR, p > 0.05 all comparisons) or on Cox multivariate analysis. Chemotherapy was associated with higher OS (65.6% vs. 51.2%, p = 0.035) and a trend towards significance on multivariate assessment (p = 0.082). Sequencing of chemotherapy and CSI dose were not associated with OS (p > 0.05 for both). Conclusions Although causation cannot be implied, neither the extent of resection nor CSI dose associated with OS in adult medulloblastoma. Chemotherapy could have utility in higher-risk patients; concurrent administration may not be beneficial, especially given therapy-induced neuro-cognitive sequelae.

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    المصدر: Cancer Research. 80:P4-12

    الوصف: Background: Clinically occult primary breast cancer (COBC) with regional lymph nodes metastasis is a rare entity, with only 0.1% of breast cancer cases presenting in this fashion. The rarity of this entity precludes its study in a prospective manner. Cancer database registries offer a unique opportunity to study COBC and evaluate various management strategies and prognostic factors. Different treatment paradigms exist, including lymph node dissection, mastectomy, radiation alone, and chemotherapy. The purpose of this study is to determine the optimal treatment paradigm for patients with COBC. Methods: The National Cancer Database (NCDB) was queried for patients with clinically occult breast cancer (cT0) and positive lymph node metastasis (cN1-3). Multivariate Cox Proportional Hazard modeling was used to determine factors independently associated with overall survival (OS). Sensitivity analysis was utilized to determine the optimal number of lymph nodes to be removed and the benefit of primary breast surgery (PBS) for patients who also received radiation therapy. Results: A total of 2713 female patients were diagnosed with stage cT0N1-3M0 breast cancer from 2004 to 2015. 758 patients with missing data were excluded, and 1955 patients remained in the analysis. Results are shown in Table 1. Median follow-up was 48.1 months. Patients who were treated with chemotherapy, radiation therapy and/or had 4 or more lymph nodes removed had better OS (p Table 1: Multivariate Cox Proportional Hazard modeling results for COBC patientsVariablen (binary variables only)Hazard ratio95% CIp-valueAge-1.031.02-1.04 Discussion: Definitive treatment of COBC with chemotherapy and radiation therapy is associated with improved OS. No survival advantage can be discerned for mastectomy or breast conserving surgery (alone or in conjunction with radiotherapy). While the survival advantage for endocrine therapy was not significant, that is likely due to short follow-up intervals. Sensitivity analysis revealed an incremental benefit for removing up to 4 lymph nodes. More extensive axillary lymph node dissections with ≥10 lymph nodes removed did not significantly improve OS. Citation Format: Raed Zuhour, Waqar Haque, Jay Messer, Gary Lewis, Neil Chevli, Bin Teh, E. Brian Butler, Andrew Farach, Sandra Hatch. Clinically occult primary breast cancer with regional lymph nodes metastasis: Management and prognostic factors [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-12-11.

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    المصدر: Breast, Vol 49, Iss, Pp 8-16 (2020)
    The Breast : official journal of the European Society of Mastology

    الوصف: Purpose Metaplastic breast cancer (MBC) is a rare, aggressive variant of breast cancer that has been associated with poor clinical outcomes, as has triple-negative breast (TNBC) cancer. Limited studies compare the clinical characteristics and prognosis of MBC to TNBC. This study uses a large, contemporary US cancer database to compare clinical characteristics and survival outcomes for patients with MBC to those with TNBC. Methods The National Cancer Database was queried for women with cT1-4N1-3M0 MBC or TNBC diagnosed between 2004 and 2013 and treated with definitive surgery. Chi-squared analysis was performed to determine differences between the cohorts. Kaplan-Meier curves compared overall survival (OS), and Cox regression determined patient factors associated with OS. Results Altogether, 55,847 patients met the inclusion criteria; 50,705 (90.8%) had TNBC and 5,142 (9.2%) had MBC. Most patients had no comorbid conditions (82%), N0 disease (71%), poorly differentiated histology (77%), received chemotherapy (87%), and received radiation therapy (60%). Amongst all patients, patients with TNBC disease were observed to have greater OS than those with MBC (5-year OS 72.0% vs 55.8%, p
    Highlights • Metaplastic breast cancer is associated with poor clinical outcomes. • Metaplastic breast cancer associated with worse survival than patients with triple negative invasive ductal carcinoma. • Radiation therapy and chemotherapy associated with improved survival for patients with metaplastic breast cancer.

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    المصدر: Journal of Contemporary Brachytherapy, Vol 12, Iss 4, Pp 303-310 (2020)
    Journal of Contemporary Brachytherapy

    الوصف: Purpose There is no current randomized data comparing the efficacy of brachytherapy and enucleation for patients with larger sized tumors. The purpose of the present study was to use a large, contemporary database to determine current practice patterns and compare survival outcomes between different management options for patients with choroidal melanoma of various sizes. Material and methods The National Cancer Database was queried (2004-2014) for histologically-confirmed choroidal melanoma for patients treated with brachytherapy versus enucleation. Chi-square test was used to compare categorized demographic and clinical variables in both arms. Kaplan-Meier analysis evaluated overall survival (OS). Cox proportional hazards assessment determined variables associated with OS. Patients were divided into cohorts representing small, medium, and large tumors. Propensity scores matching (PSM) was utilized to compare more similar cohorts. Results A total of 7,096 patients met the selection criteria; 5,501 (78%) patients received brachytherapy and 1,595 (22%) patients were treated with enucleation. After PSM, 5-yr OS for small tumors was 87% vs. 64%, for medium tumors was 77% vs. 57%, and for large tumors was 68% vs. 46% for brachytherapy and enucleation, respectively (p < 0.001). Following PSM, multivariate Cox regression found older age (hazard ratio [HR] = 1.76, 95% confidence interval [CI] = 1.51-2.06), more comorbidities (HR = 1.46, 95% CI = 1.25-1.70), extraocular extension (EOE) (HR = 1.25, 95% CI = 1.06-1.48), ciliary body invasion (CBI) (HR = 1.20, 95% CI = 1.02-1.40), and larger size (HR = 1.52, 95% CI = 1.40-1.66) were negative prognosticators of survival. Brachytherapy was a positive prognosticator of survival (HR = 0.45, 95% CI = 0.40-0.51). Conclusions Patients selected for brachytherapy had improved survival compared to enucleation in all size cohorts. EOE and CBI are significantly higher in the enucleation cohort and are important negative prognosticators for survival selected against patients having brachytherapy. Brachytherapy is a reasonable treatment option for certain patients with large size tumors.

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    المصدر: Clinical Genitourinary Cancer. 17:e1069-e1079

    الوصف: Muscle-invasive bladder cancer (MIBC) may be managed with radical cystectomy (RC) or chemoradiotherapy (CRT). Because patient selection for RC is important to avoid treatment-related mortality, this study addressed a knowledge gap by quantifying short-term mortality with both approaches, as well as predictors thereof.The National Cancer Database was queried (2004-2014) for clinically staged T2-4aN0M0 MIBC that received either CRT or RC. Statistics included cumulative incidence comparisons of 30- and 90-day mortality between patients treated with either CRT or RC and Cox regression to evaluate predictors thereof.Of 16,658 patients, 15,208 (91.3%) underwent RC and 1450 (8.7%) CRT. Crude rates of post-treatment mortality at 30 days were 2.7% versus 0.6% (P .001) and at 90 days were 7.5% versus 4.5% (P = .017) for patients treated with RC and CRT, respectively. When stratifying by age, worse 30- and 90-day mortality with RC was observed for patients aged ≥ 76 years.This study describes 30- and 90-day mortality following RC versus CRT. Both approaches yield statistically similar treatment-related mortality rates in patients ≤ 75 years of age; however, worse post-treatment mortality was observed with use of RC in patients ≥ 76 years of age. These results may be utilized to better inform shared decision-making between patients and providers when weighing both RC and CRT for MIBC.

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    المصدر: Cancer Communications, Vol 39, Iss 1, Pp 1-9 (2019)
    Cancer Communications

    الوصف: Background Invasive micropapillary carcinoma (IMPC) is an uncommon subtype of breast cancer. Previous studies of this subtype demonstrated a higher propensity for lymph node metastases as compared with invasive ductal carcinoma (IDC). The purpose of the present study was to determine the clinical characteristics, outcomes, and propensity for lymph node metastasis of patients with IMPC of the breast recorded in the National Cancer Database (NCDB). Methods Records of patients with IMPC diagnosed between 2004 and 2014 were retrieved from the NCDB. Log-rank test was performed to evaluate associations of clinical characteristics with overall survival (OS). Cox proportional hazards model was used to determine variables associated with OS. Results Overall, 2660 patients with IMPC met the selection criteria; the 5-year OS rate was 87.5% and 24.9% of patients had nodal involvement at presentation. Patients with ≥ 4 positive lymph nodes had shorter OS than node-negative patients, whereas patients with 1–3 positive nodes had similar OS to node-negative patients. Age

  10. 10

    المصدر: Biomedicines, Vol 9, Iss 1561, p 1561 (2021)
    Biomedicines
    Volume 9
    Issue 11

    الوصف: Biofouling is the unwanted adsorption of cells, proteins, or intracellular and extracellular biomolecules that can spontaneously occur on the surface of metal nanocomplexes. It represents a major issue in bioinorganic chemistry because it leads to the creation of a protein corona, which can destabilize a colloidal solution and result in undesired macrophage-driven clearance, consequently causing failed delivery of a targeted drug cargo. Hyaluronic acid (HA) is a bioactive, natural mucopolysaccharide with excellent antifouling properties, arising from its hydrophilic and polyanionic characteristics in physiological environments which prevent opsonization. In this study, hyaluronate-thiol (HA-SH) (MW 10 kDa) was used to surface-passivate gold nanoparticles (GNPs) synthesized using a citrate reduction method. HA functionalized GNP complexes (HA-GNPs) were characterized using absorption spectroscopy, scanning electron microscopy, zeta potential, and dynamic light scattering. GNP cellular uptake and potential dose-dependent cytotoxic effects due to treatment were evaluated in vitro in HeLa cells using inductively coupled plasma—optical emission spectrometry (ICP-OES) and trypan blue and MTT assays. Further, we quantified the in vivo biodistribution of intratumorally injected HA functionalized GNPs in Lewis Lung carcinoma (LLC) solid tumors grown on the flank of C57BL/6 mice and compared localization and retention with nascent particles. Our results reveal that HA-GNPs show overall greater peritumoral distribution (** p <
    0.005, 3 days post-intratumoral injection) than citrate-GNPs with reduced biodistribution in off-target organs. This property represents an advantageous step forward in localized delivery of metal nano-complexes to the infiltrative region of a tumor, which may improve the application of nanomedicine in the diagnosis and treatment of cancer.

    وصف الملف: application/pdf