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#31968225   // Save this To Up

Expression of estrogen receptor α variants and c-Fos in rat mammary gland and tumors.

Breast cancer is currently the leading cause of cancer death among women worldwide. AP-1 (c-Fos/c-Jun) is associated with proliferation and survival, while cytoplasmic c-Fos activates phospholipid synthesis in cells induced to differentiate or grow. Estrogen receptor α 46 (ERα46) is a splice variant of full-length ERα66 and it is known that it has an inhibitory role in cancer cell growth. We investigated c-Fos localization, its relationship to AP-1, the non genomic pathway of phospho-Tyr537-ERα66, as well as ERα46 and ERα66 isoforms in rat mammary gland development and carcinogenic transformation, and in mammary tumors. Female rats were injected: a) saline solution (Control mammary gland, CMG) or b) N-Nitroso-N-methyl urea (NMU), and samples were taken at 60, 90, 120 and 150 days of life. In addition, we analyzed hormone-dependent (HD) and independent (HI) tumors in ovariectomized rats, and intact tumors (IT) in non-ovariectomized ones. Our results show that, in CMG, nuclear c-Fos and proliferation decreased with age, AP-1 content was low, and nuclear ERα46/ERα66 ratio was higher than 1. In NMU, nuclear c-Fos and proliferation increased with carcinogenic transformation, AP-1 content was high, and nuclear ERα46/ERα66 was below 1. As tumor grade increased, proliferation, nuclear c-Fos and AP-1 expression were negatively associated to nuclear ERα46/ERα66 in IT. In HD, nuclear ERα46/ERα66, nuclear c-Fos expression, AP-1 levels and proliferation were lower than in HI, whose growth is estrogen-independent. Phospho-Tyr537-ERα66 content and ERK1/2 activation were associated with AP-1 levels and cell proliferation. Collectively, our findings support the notion that variant detection and ERα46/ERα66 ratio could shed light on the role of ERα isoforms in mammary gland transformation and the behavior of ERα positive mammary tumors.

1814 related Products with: Expression of estrogen receptor α variants and c-Fos in rat mammary gland and tumors.

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#31968134   // Save this To Up

Oral bisphosphonate use and all-cause mortality in patients with moderate-severe (grade 3B-5D) chronic kidney disease: a population-based cohort study.

Oral Bisphosphonates (oBP) have been associated with reduced fractures and mortality. However, their risks and benefits are unclear in patients with moderate-severe CKD. This study examined the association between oBP and all-cause mortality in G3B-5D CKD. This is a population-based cohort study including all subjects with an eGFR<45/ml/min/1.73m aged 40+ years from the UK Clinical Practice Research Datalink (CPRD) and the Catalan Information System for Research in Primary Care (SIDIAP). Previous and current users of other anti-osteoporosis drugs were excluded. oBP use was modelled as a time-varying exposure to avoid immortal time bias. Treatment episodes in oBP users were created by concatenating prescriptions until patients switched or stopped therapy or were censored or died. A washout period of 180 days was added to (date of last prescription +180 days). Propensity scores (PS) were calculated using pre-specified predictors of mortality including age, gender, baseline eGFR, socio-economic status, co-morbidities, previous fracture, co-medications and number of hospital admissions in the previous year. Cox models were used for PS adjustment before and after PS trimming (the first and last quintiles). In the CPRD, of 19,351 oBP users and 210,954 non-oBP users, 5,234 (27%) and 85,105 (40%) deaths were recorded over 45,690 and 915,867 person-years of follow-up, respectively. oBP users had 8% lower mortality risk compared to non-oBP users (HR 0.92, 95% CI 0.89-0.95). Following PS trimming, this became non-significant (HR 0.98, 95% CI 0.94-1.04). In the SIDIAP, of 4,146 oBP users 86,127 non-oBP users, 1,330 (32%) and 36,513 (42%) died, respectively. oBP were not associated with mortality in PS adjustment and trimming (HR 1.04, 95% CI 0.99-1.1 and HR 0.95, 95% CI 0.89-1.01). In this observational, patient-based cohort study, oBP were not associated with increased mortality amongst patients with moderate-severe CKD. However, further studies are needed on other effects of oBP in CKD patients. This article is protected by copyright. All rights reserved.

2148 related Products with: Oral bisphosphonate use and all-cause mortality in patients with moderate-severe (grade 3B-5D) chronic kidney disease: a population-based cohort study.

Kidney disease spectrum ( Pancreatic disease spectr Kidney cancer survey tiss Kidney cancer survey tiss Kidney cancer tissue arra Ovary disease spectrum (o Advanced kidney cancer ti Lung disease spectrum tis Kidney cancer survey tiss Oral squamous cell cancer Breast disease spectrum t Small intestine disease s

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Immunohistochemical analysis of cancer-associated fibroblasts and podoplanin in head and neck cancer.

To immunohistochemically evaluate the association between the presence of cancer-associated fibroblasts (CAFs) and the tumour expression of podoplanin (PDPN) in head and neck squamous cell carcinoma (HNSCC) and their association with clinicopathological variables.

1893 related Products with: Immunohistochemical analysis of cancer-associated fibroblasts and podoplanin in head and neck cancer.

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Sequential intra-arterial infusion of 90Y-resin microspheres and mitomycin C in chemo refractory liver metastatic breast cancer patients: a single centre pilot study.

Background The aim of the study was to evaluate the safety and feasibility of intra-arterial mitomycin C (MMC) infusion after selective internal radiation therapy (SIRT) using Yttrium-90 (90Y) resin microspheres in liver metastatic breast cancer (LMBC) patients. Patients and methods The prospective pilot study included LMBC patients from 2012-2018. Patients first received infusion of 90Y resin microspheres, after 6-8 weeks response to treatment was assessed by MRI, 18F-FDG PET/CT and laboratory tests. After exclusion of progressive disease, MMC infusion was administrated 8 weeks later in different dose cohorts; A: 6 mg in 1 cycle, B: 12 mg in 2 cycles, C: 24 mg in 2 cycles and D: maximum of 72 mg in 6 cycles. In cohort D the response was evaluated after every 2 cycles and continued after exclusion of progressive disease. Adverse events (AE) were reported according to CTCAE version 5.0. Results Sixteen patients received 90Y treatment. Four patients were excluded for MMC infusion, because of extra hepatic disease progression (n = 3) and clinical and biochemical instability (n = 1). That resulted in the following number of patient per cohort; A: 2, B: 1, C: 3 and D: 6. In 4 of the 12 patients (all cohort D) the maximum dose of MMC was adjusted due biochemical toxicities (n = 2) and progressive disease (n = 2). One grade 3 AE occurred after 90Y treatment consisting of a gastrointestinal ulcer whereby prolonged hospitalization was needed. Conclusions Sequential treatment of intra-arterial infusion of MMC after 90Y SIRT was feasible in 75% of the patients when MMC was administrated in different escalating dose cohorts. However, caution is needed to prevent reflux after 90Y SIRT in LMBC patients.

1757 related Products with: Sequential intra-arterial infusion of 90Y-resin microspheres and mitomycin C in chemo refractory liver metastatic breast cancer patients: a single centre pilot study.

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#31967910   // Save this To Up

Alfuzosin hydrochloride-loaded low-density gastroretentive sponges: Development, characterization and gastroretentive monitoring in healthy volunteers via MRI.

The current work aimed to develop low-density gastroretentive sponges loaded with alfuzosin HCl (ALF) to sustain the rate of drug release, improve its oral bioavailability and deliver it to the main site of absorption. Sponges were developed, according to a 2 full factorial design, by compression of the lyophilized ALF-loaded hydroxypropylmethylcellulose (HPMC) or chitosan (CH) solutions. The influences of the polymer type, grade and concentration on the appearance, topography, porosity, density, ALF release, floating behavior, swelling, erosion, and mucoadhesive potential of the developed sponges were explored. Based on the desirability value, the best achieved system was selected. The gastroretentive potential of this system was evaluated in healthy male volunteers via MRI. Soft and flexible sponges were developed. They were characterized with interconnecting pores and channels and had excellent floating properties with respect to floating lag time and duration. Compared to HPMC-based sponges, CH-based ones exhibited higher porosity, larger pore diameters, lower bulk densities, higher drug release rates, larger swelling ratios, faster erosion rates and better mucoadhesive properties. MRI of magnetite-loaded best-achieved CH-based system (F8) ascertained the development of a promising gastroretentive system; exhibiting a gastric residence period of at least 5 h.

2158 related Products with: Alfuzosin hydrochloride-loaded low-density gastroretentive sponges: Development, characterization and gastroretentive monitoring in healthy volunteers via MRI.

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Hyperthermic intraperitoneal chemotherapy does not improve survival in advanced ovarian cancer.

Despite its widespread use, until recently, there was no randomized evidence for hyperthermic intraperitoneal chemotherapy (HIPEC) versus surgery without HIPEC for ovarian cancer. Recently, a Dutch study (OVHIPEC) reported benefits in both progression-free survival (PFS) and overall survival (OS) gained from the use of HIPEC at the time of interval debulking surgery (IDS) for stage III ovarian carcinoma, whereas a Korean randomized trial failed to show a benefit of HIPEC for patients with ovarian cancer undergoing primary debulking surgery or IDS. In colorectal cancer, 2 randomized trials failed to show an improvement in survival with HIPEC. In addition to these contradictory results, there are a number of aspects of the Dutch OVHIPEC trial in ovarian cancer that can be criticized. Some criticisms include a reduction of the number of patients needed to be randomized because of too slow accrual; much lower PFS and OS in both arms than expected according to the statistical plan; the small size of the study, with imbalances between the 2 arms (eg, more low-grade tumors in the HIPEC arm); the timing of randomization before the start of IDS; the lack of clear inclusion criteria for neoadjuvant chemotherapy; and the heterogeneity of the results, with the largest effect shown at the smaller centers. Furthermore, it is questionable whether the adverse events were reported completely. In conclusion, data about HIPEC for ovarian cancer in general are not convincing, and they do not change the standard of care, which remains for ovarian cancer surgery and intravenous chemotherapy.

2469 related Products with: Hyperthermic intraperitoneal chemotherapy does not improve survival in advanced ovarian cancer.

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Do all patients with recurrent ovarian cancer need systemic therapy?

The scientific organizing committee of the 12th International Symposium on Advanced Ovarian Cancer: Optimal Therapy. Update proposed the question regarding whether all patients with recurrent ovarian cancer (ROC) need systemic therapy. This article has addressed this question and focused on the clinical scenarios in which the benefits of systemic therapy in patients with ROC are limited, including the frail elderly and patients with multiple medical comorbidities, as well as a subset of patients with platinum-resistant ovarian cancer who have a particularly poor prognosis with a short survival. The challenges of identifying and selecting which patients are unlikely to benefit from systemic therapy were addressed. The benefit of systemic therapy also can be questioned in specific histological subtypes of ROC such as low-grade serous cancers as well as clear cell and mucinous cancers in view of low response rates. Finally, the contentious question regarding the timing of chemotherapy in asymptomatic patients with CA 125 disease progression after response to first-line chemotherapy was addressed and an argument made challenging the current treatment paradigm. Clearly, not all patients with ROC need or should be offered systemic therapy, and ultimately the recommendations need to be based on evidence and communicated in a clear and sensitive manner to patients and their families.

2300 related Products with: Do all patients with recurrent ovarian cancer need systemic therapy?

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Pharmacogenetics and pharmacokinetics modeling of unexpected and extremely severe toxicities after sorafenib intake.

A 53-year-old woman with papillary thyroid cancer treated with 800 mg sorafenib therapy rapidly experienced grade 3 toxicities. Dosing was reduced in a step-wise manner with several treatment discontinuations down to 200 mg every 2 days but severe toxicities continued. Plasma drug monitoring showed high exposure, even at low dose. Dosing was then further reduced at 200 mg every 3 days and tolerance was finally acceptable (i.e., grade 1 toxicity) with stable disease upon RECIST imaging. Pharmacogenetic investigations showed polymorphisms affecting both UGT1A9 (-rs3832043) and nuclear receptor PXR (-rs3814055-rs2472677 and -rs10934498), possibly resulting in downregulation of liver metabolizing enzymes of sorafenib (i.e., CYP and UGT). Patient's clearance (0.48 l/h) estimated by Bayesian approach was consistently lower than usually described. This is the first time that, in addition to mutations affecting , genetic polymorphisms of have possibly been associated with both plasma overexposure and severe toxicities upon sorafenib intake.

1789 related Products with: Pharmacogenetics and pharmacokinetics modeling of unexpected and extremely severe toxicities after sorafenib intake.

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#31967359   // Save this To Up

Deceased vs living donor grafts for pediatric simultaneous liver-kidney transplantation: A single-center experience.

In conditions of limited experience of pediatric simultaneous liver-kidney transplantation (SLKT) using grafts from living and deceased donors, there is a certain need to validate the approach.

1043 related Products with: Deceased vs living donor grafts for pediatric simultaneous liver-kidney transplantation: A single-center experience.

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#31967298   // Save this To Up

The prognostic value of lncRNA SNHG4 and its potential mechanism in liver cancer.

Emerging evidence shows that noncoding RNA functions as new gene regulators and prognostic markers in several cancers, including liver cancer. Here, we focused on the Small Nucleolar RNA Host Gene 4 (SNHG4) in liver cancer prognosis based on The Cancer Genome Atlas (TCGA) data.

1528 related Products with: The prognostic value of lncRNA SNHG4 and its potential mechanism in liver cancer.

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