Calculated versus Measured MVV—Surrogate Marker of Ventilatory Capacity in Pediatric CPET

Introduction. Patients with surgical menopause have a risk for osteopenic syndrome (OS). Menopausal hormone therapy (MHT) in combination with calcium and vitamin D promotes increase in bone mineral density (BMD). The expression level of vitamin D receptor in mononuclear fraction cells (MNFC) of blood can be considered as a predictive marker of effectiveness of OS therapy. Aim. To search a molecular predictive marker of the effectiveness of OS treatment. Materials and methods. The study included 100 women aged 4055 years with a duration of surgical menopause from 12 months to 6 years. The criterion for including patients in the study was the absence of contraindications to the use of MHT. The subject of the study was the determination of BMD by dual-energy X-ray absorptiometry, polymerase chain reaction diagnostics of the level of expression of vitamin D genes, estradiol and progesterone receptors, determination of 25-OH vitamin D in the blood. Results. Analysis of 12-month OS therapy effectiveness evaluated with a surrogate marker BMD. The increase in BMD up to 34% per year was treated as absence of negative dynamics, more than 4% per year as positive one. Significant effect of combination therapy compared with MHT on BMD in patients with surgical menopause with a low baseline level of BMD (due to hypovitaminosis D) is associated with the anti-inflammatory, bone-protective effect of vitamin D. In both groups of patients not responding; to the prescribed therapy we were able to conduct a comparative analysis of expression level of the target molecules in the MNFC before the start of treatment. The efficacy of MHT and combination therapy for BMD disorders is positively associated with the expression level of vitamin D receptors in MNFC before treatment. Therefore, the vitDR mRNA level is a potential predictive marker of the effectiveness of OS treatment. The expression levels of nuclear estradiol beta receptor and membrane receptor for progesterone in MNFC before treatment showed an upward trend in women responding to therapy. Conclusion. The expression level of the vitamin D receptor in MNFC of blood is significantly lower in the group of women with no/insufficient effect on 12-month combined therapy. This indicator can be considered as a predictive marker of the effectiveness of OS therapy.

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Paeonol Inhibits Prostate Cancer Cell Invasion and Epithelial-Mesenchymal Transformation by Inactivation of STAT3 Pathway

Current Topics in Nutraceutical Research ◽

10.37290/ctnr2641-452x.19:15-20 ◽

2020 ◽

Vol 19 (1) ◽

pp. 15-20

Author(s):

Junyi Xiang ◽

Feng Huang ◽

Renhua Huang ◽

Jingzhan Su ◽

Yulong Liu

Keyword(s):

Prostate Cancer ◽

Treatment Options ◽

Surrogate Marker ◽

Cytotoxic Agents ◽

Potential Candidate ◽

Dependent Manner ◽

Ablation Therapy ◽

Androgen Ablation ◽

Mesenchymal Transformation ◽

Dose Dependent

Prostate cancer is one of the leading causes of death in men all over the world. Treatment options such as androgen ablation therapy and cytotoxic agents have many undesirable side effects, narrow therapeutic windows, or other limitations. In this research, we have explored the effects of paeonol on prostate cancer and its mechanism of action. Our results have shown that paeonol reduced the viability of prostate cancer cells in a dose-dependent manner. The wound-healing assay, a surrogate marker of tumor metastasis, showed that the relative wound width of 10 µM group was less than that of 50 µM paeonol-treated cells. Besides, the results of the transwell assay also showed that the number of migrated cells was significantly lower after treatment with 50 µM paeonol compared to the 10 µM group. The Western blot results showed that paeonol treatment induced a decrease in the mesenchymal markers (vimentin and N-cadherin), while the epithelial marker (E-cadherin) increased in a dose-dependent manner suggesting that paeonol effectively inhibits the epithelial-mesenchymal transformation in PC3 cells. Furthermore, the expression of STAT3 and p-STAT3 was also decreased after paeonol treatment, which indicated that the STAT3 signaling pathway was inhibited by paeonol. To conclude, the results summarized in this paper suggest that paeonol could be a potential candidate in the treatment of prostate cancer.

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Serum KIAA1199 Is a Surrogate Marker for Epithelial-Mesenchymal Transition that Predicts the Postoperative Metastasis and Prognosis of Cholangiocarcinoma

SSRN Electronic Journal ◽

10.2139/ssrn.3409293 ◽

2019 ◽

Author(s):

Xiangyu Zhai ◽

Wei Wang ◽

Yunlong Ma ◽

Yijia Zeng ◽

Dandan Dou ◽

...

Keyword(s):

Epithelial Mesenchymal Transition ◽

Surrogate Marker ◽

Mesenchymal Transition

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Genetic susceptibilities and prediction modeling of carbamazepine and allopurinol-induced severe cutaneous adverse reactions in Vietnamese

Pharmacogenomics ◽

10.2217/pgs-2019-0146 ◽

2020 ◽

Author(s):

Dinh van Nguyen ◽

Hieu Chi Chu ◽

Christopher Vidal ◽

Richard B Fulton ◽

Nguyet Nhu Nguyen ◽

...

Keyword(s):

Adverse Reactions ◽

Surrogate Marker ◽

Hypersensitivity Syndrome ◽

Stevens Johnson Syndrome ◽

Strongly Correlated ◽

Drug Induced ◽

Johnson Syndrome ◽

Severe Cutaneous Adverse Reactions ◽

Systemic Symptoms ◽

Cutaneous Adverse Reactions

Aims: To determine genetic susceptibility markers for carbamazepine (CBZ) and allopurinol-induced severe cutaneous adverse reactions (SCARs) in Vietnamese. Methods: A case control study was performed involving 122 patients with CBZ or allopurinol induced SCARs and 120 drug tolerant controls. Results: HLA-B*58:01 was strongly associated with allopurinol-induced SCARs and strongly correlated with SNP rs9263726. HLA-B*15:02 was associated with CBZ-induced Stevens–Johnson syndrome/toxic epidermal necrolysis but not with drug-induced hypersensitivity syndrome/drug rash with eosinophilia and systemic symptoms. No association was found between HLA-A*31:01 and CBZ-induced SCARs. HLA-B*58:01 and rs3909184 allele A with renal insufficiency were shown to increase the risk of allopurinol-induced SCARs. Conclusion: HLA-B*58:01 and HLA-B*15:02 confer susceptibility to allopurinol-induced SCARs and CBZ-induced SJS/TEN in Vietnamese. Single nucleotide polymorphism rs9263726 can be used as a surrogate marker in identifying HLA-B*58:01.

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The ENT emergency clinic: does senior input matter?

The Journal of Laryngology & Otology ◽

10.1017/s0022215112002538 ◽

2012 ◽

Vol 127 (1) ◽

pp. 15-19 ◽

Cited By ~ 5

Author(s):

A Mirza ◽

L McClelland ◽

M Daniel ◽

N Jones

Keyword(s):

Quality Of Care ◽

Discharge Rate ◽

Surrogate Marker ◽

Operating Theatre ◽

Number Of Children ◽

Discharge Rates ◽

Time Period ◽

Number Of Patients

AbstractBackground:Many ENT conditions can be treated in the emergency clinic on an ambulatory basis. Our clinic traditionally had been run by foundation year two and specialty trainee doctors (period one). However, with perceived increasing inexperience, a dedicated registrar was assigned to support the clinic (period two). This study compared admission and discharge rates for periods one and two to assess if greater registrar input affected discharge rate; an increase in discharge rate was used as a surrogate marker of efficiency.Method:Data was collected prospectively for patients seen in the ENT emergency clinic between 1 August 2009 and 31 July 2011. Time period one included data from patients seen between 1 August 2009 and 31 July 2010, and time period two included data collected between 1 August 2010 and 31 July 2011.Results:The introduction of greater registrar support increased the number of patients that were discharged, and led to a reduction in the number of children requiring the operating theatre.Conclusion:The findings, which were determined using clinic outcomes as markers of the quality of care, highlighted the benefits of increasing senior input within the ENT emergency clinic.

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Current Concepts of Pediatric Acute Kidney Injury—Are We Ready to Translate Them into Everyday Practice?

Journal of Clinical Medicine ◽

10.3390/jcm10143113 ◽

2021 ◽

Vol 10 (14) ◽

pp. 3113

Author(s):

Kinga Musiał

Keyword(s):

Acute Kidney Injury ◽

Surrogate Marker ◽

Kidney Injury ◽

Tubuloglomerular Feedback ◽

Everyday Practice ◽

Special Focus ◽

Functional Reserve ◽

Renal Functional Reserve ◽

Acute Kidney Disease ◽

Pediatric Acute Kidney Injury

Pediatric acute kidney injury (AKI) is a major cause of morbidity and mortality in children undergoing interventional procedures. The review summarizes current classifications of AKI and acute kidney disease (AKD), as well as systematizes the knowledge on pathophysiology of kidney injury, with a special focus on renal functional reserve and tubuloglomerular feedback. The aim of this review is also to show the state-of-the-art in methods assessing risk and prognosis by discussing the potential role of risk stratification strategies, taking into account both glomerular function and clinical settings conditioned by fluid overload, urine output, or drug nephrotoxicity. The last task is to suggest careful assessment of eGFR as a surrogate marker of renal functional reserve and implementation of point-of-care testing, available in the case of biomarkers like NGAL and [IGFBP-7] × [TIMP-2] product, into everyday practice in patients at risk of AKI due to planned invasive procedures or treatment.

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Exposure of the cytoplasm to low-dose X-rays modifies ataxia telangiectasia mutated-mediated DNA damage responses

Scientific Reports ◽

10.1038/s41598-021-92213-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Munetoshi Maeda ◽

Masanori Tomita ◽

Mika Maeda ◽

Hideki Matsumoto ◽

Noriko Usami ◽

...

Keyword(s):

Dna Damage ◽

Cell Death ◽

Ataxia Telangiectasia ◽

Kinase Inhibitor ◽

Surrogate Marker ◽

X Rays ◽

Ataxia Telangiectasia Mutated ◽

Whole Cell ◽

X Ray ◽

Dna Damage Responses

AbstractWe recently showed that when a low X-ray dose is used, cell death is enhanced in nucleus-irradiated compared with whole-cell-irradiated cells; however, the role of the cytoplasm remains unclear. Here, we show changes in the DNA damage responses with or without X-ray microbeam irradiation of the cytoplasm. Phosphorylated histone H2AX foci, a surrogate marker for DNA double-strand breaks, in V79 and WI-38 cells are not observed in nucleus irradiations at ≤ 2 Gy, whereas they are observed in whole-cell irradiations. Addition of an ataxia telangiectasia mutated (ATM) kinase inhibitor to whole-cell irradiations suppresses foci formation at ≤ 2 Gy. ABL1 and p73 expression is upregulated following nucleus irradiation, suggesting the induction of p73-dependent cell death. Furthermore, CDKN1A (p21) is upregulated following whole-cell irradiation, indicating the induction of cell cycle arrest. These data reveal that cytoplasmic radioresponses modify ATM-mediated DNA damage responses and determine the fate of cells irradiated at low doses.

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