scholarly journals Distribution of 5-Hydroxymethylcytosine in Different Human Tissues

2011 ◽  
Vol 2011 ◽  
pp. 1-5 ◽  
Author(s):  
Weiwei Li ◽  
Min Liu
Keyword(s):  
Colorectal Cancer ◽  
Human Tissues ◽  
Colorectal Tissue ◽  
First Time ◽  
Normal Colorectal Tissue ◽  
Different Tissues

5-hydroxymethylcytosine (5-hmC) is a modified form of cytosine recently found in mammalians and is believed, like 5-methylcytosine, to also play an important role in switching genes on and off. By utilizing a newly developed 5-hmC immunoassay, we determined the abundance of 5-hmC in human tissues and compared 5-hmC states in normal colorectal tissue and cancerous colorectal tissue. Significant differences of 5-hmC content in different tissues were observed. The percentage of 5-hmC measured is high in brain, liver, kidney and colorectal tissues (0.40–0.65%), while it is relatively low in lung (0.18%) and very low in heart, breast, and placenta (0.05-0.06%). Abundance of 5-hmC in the cancerous colorectal tissues was significantly reduced (0.02–0.06%) compared to that in normal colorectal tissues (0.46–0.57%). Our results showed for the first time that 5-hmC distribution is tissue dependent in human tissues and its abundance could be changed in the diseased states such as colorectal cancer.

scholarly journals Subcellular localization of HMGB1 in colorectal cancer impacts on tumor grade and survival prognosis

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Chao-Qun Wang ◽  
Bi-Fei Huang ◽  
Yan Wang ◽  
Chih-Hsin Tang ◽  
Hong-Chuan Jin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colorectal Adenoma ◽  
Prognostic Significance ◽  
Tumor Grade ◽  
Hmgb1 Protein ◽  
Survival Prognosis ◽  
Tissue Samples ◽  
Colorectal Tissue ◽  
Hmgb1 Expression ◽  
Normal Colorectal Tissue

Abstract The high-mobility group box-1 (HMGB1) protein is implicated in the development of various cancers and their proliferation. According to its function, HMGB1 shuttles between the cell nucleus and cytoplasm, assisting with nucleosome stabilization and gene transcription, or localizing in the cell membrane for outgrowth. The clinicopathologic and prognostic significance of these different subcellular locations and their correlation has been unclear in colorectal cancer (CRC). We found significantly higher rates of nuclear HMGB1 expression in CRC and colorectal adenoma tissue samples (84.0% and 92.6%, respectively) than in normal colorectal tissue (15.0%) and a significantly higher rate of positive cytoplasmic HMGB1 expression in CRC tissue (25.2%) compared with colorectal adenoma (11.8%) and normal colorectal tissue (0.0%). Positive cytoplasmic HMGB1 expression was associated with high-grade CRC, a poor prognosis, and was negatively correlated with strongly positive nuclear HMGB1 expression in CRC tissue specimens (r = – 0.377, P = 0.000). CRC patients with strongly positive nuclear HMGB1 expression had a better survival prognosis than other CRC patients. Preventing nuclear plasma translocation of HMGB1 may be a new strategy for CRC management.

Differentiation of Tumour from Normal Colorectal Tissue by SELDI-MS Protein Profiling

Endoscopy ◽  
2004 ◽  
Vol 36 (05) ◽  
Author(s):  
AM Lennon ◽  
D Stuart ◽  
AC Tan ◽  
E Fox ◽  
KS Sheahan ◽  
...  
Keyword(s):  
Protein Profiling ◽  
Colorectal Tissue ◽  
Normal Colorectal Tissue

Laminin 521 Modulates the Сytotoxic Effect of 5-Fluorouracil on Colorectal Cancer HT29 Cells

2019 ◽  
Vol 35 (6) ◽  
pp. 73-79
Author(s):  
A. Turchinovich ◽  
I.M. Tsypina ◽  
V.G. Zgoda ◽  
S.V. Nikulin ◽  
D.V. Maltseva
Keyword(s):  
Colorectal Cancer ◽  
Cytotoxic Effect ◽  
Mechanisms Of Action ◽  
Ht29 Cell ◽  
Β1 Integrin ◽  
Russian Science ◽  
Apoptotic Gene ◽  
Ht29 Cells ◽  
First Time ◽  
Ht29 Cell Line

The cytotoxic effect of 5-fluorouracil (5FU) and regorafenib (RF)-drugs with different mechanisms of action used to treat colorectal cancer-on the HT29 cell line when cultured on plastic and laminin 521 (LM-521) has been studied. It was shown for the first time that LM-521 can increase the sensitivity of tumor cells to 5FU. Based on the analysis of the transcriptome and proteome, a possible mechanism of the observed effect of LM-521 on HT29 cell viability was proposed. The interaction of β1-containing integrins on the cell surface with LM-521 can activate the FAK/PI3K/Akt signaling pathways, promote phosphorylation of the YAP transcription coactivator and its binding to a complex with the 14-3-3σ protein. The formation of such complex leads to the YAP retention in the cytoplasm, prevents its transport to the nucleus and the activation of anti-apoptotic gene transcription. apoptosis, β1 integrin, colorectal cancer, laminin 521 (laminin-11), regorafenib, 5-fluorouracil, HT29, ITGB1, LAMA5, YAP, SFN, 14-3-3σ The study was funded by the Russian Science Foundation (Project 17-14-01338).

scholarly journals Bark traits, decomposition and flammability of Australian forest trees

2017 ◽  
Vol 65 (4) ◽  
pp. 327 ◽  
Author(s):  
Saskia Grootemaat ◽  
Ian J. Wright ◽  
Peter M. van Bodegom ◽  
Johannes H. C. Cornelissen ◽  
Veronica Shaw
Keyword(s):  
Forest Tree ◽  
Remarkable Feature ◽  
Interspecific Differences ◽  
Eucalypt Plantations ◽  
Physical Traits ◽  
Key Driver ◽  
Multiple Species ◽  
Species Specific ◽  
First Time ◽  
Different Tissues

Bark shedding is a remarkable feature of Australian trees, yet relatively little is known about interspecific differences in bark decomposability and flammability, or what chemical or physical traits drive variation in these properties. We measured the decomposition rate and flammability (ignitibility, sustainability and combustibility) of bark from 10 common forest tree species, and quantified correlations with potentially important traits. We compared our findings to those for leaf litter, asking whether the same traits drive flammability and decomposition in different tissues, and whether process rates are correlated across tissue types. Considerable variation in bark decomposability and flammability was found both within and across species. Bark decomposed more slowly than leaves, but in both tissues lignin concentration was a key driver. Bark took longer to ignite than leaves, and had longer mass-specific flame durations. Variation in flammability parameters was driven by different traits in the different tissues. Decomposability and flammability were each unrelated, when comparing between the different tissue types. For example, species with fast-decomposing leaves did not necessarily have fast-decomposing bark. For the first time, we show how patterns of variation in decomposability and flammability of bark diverge across multiple species. By taking species-specific bark traits into consideration there is potential to make better estimates of wildfire risks and carbon loss dynamics. This can lead to better informed management decisions for Australian forests, and eucalypt plantations, worldwide.

Pathogenesis of osteoarthritis

2013 ◽  
pp. 1165-1173
Author(s):  
Tonia L. Vincent ◽  
Linda Troeberg
Keyword(s):  
Therapeutic Strategies ◽  
Molecular Pathways ◽  
Disease Development ◽  
Rodent Models ◽  
Disease Pathogenesis ◽  
Recent Success ◽  
Epidemiological Risk ◽  
Experimental Approaches ◽  
First Time ◽  
Different Tissues

Understanding pathogenic mechanism in disease is critical for development of targeted therapeutic strategies. Although there are, at this time, only a handful of experimental approaches for treating osteoarthritis (OA), until 10 years ago this disease was almost universally considered an unmodifiable condition. Emerging data during this time, largely fuelled by studies in rodent models, has completely changed the paradigm of disease pathogenesis and has for the first time, generated novel, realistic targets for this highly prevalent and disabling condition. These targets include the aggrecanases, members of the ADAMTS family, and collagenases, which together are critical for the early breakdown of the extracellular matrix of cartilage. Some recent success has also been demonstrated by targeting bone in disease. Development of pain in OA is complex and likely arises from different tissues at different stages of disease. In the following section we describe the pathological features of OA, and discuss the evolution of theories of OA pathogenesis and factors that have limited mechanistic clarity in this disease. We summarize the molecular pathways that are now known to be active in disease, and consider how these identified molecular pathways could be linked to known epidemiological risk factors. We finish by discussing possible future therapeutic strategies that will emerge from these discoveries and the current limitations in implementing new therapies in OA.

scholarly journals Analysis of the Carry-Over of Ochratoxin A from Feed to Milk, Blood, Urine, and Different Tissues of Dairy Cows Based on the Establishment of a Reliable LC-MS/MS Method

Molecules ◽  
2019 ◽  
Vol 24 (15) ◽  
pp. 2823 ◽  
Author(s):  
Zhiqi Zhang ◽  
Zhichen Fan ◽  
Dongxia Nie ◽  
Zhihui Zhao ◽  
Zheng Han
Keyword(s):  
Dairy Cows ◽  
Ochratoxin A ◽  
Limit Of Quantification ◽  
Fresh Milk ◽  
Liquid Chromatography Tandem Mass ◽  
Ochratoxin Α ◽  
Carry Over ◽  
First Time ◽  
Different Tissues

A rapid and reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for simultaneous determination of ochratoxin A (OTA) and its metabolite ochratoxin α (OTα), for the first time, in dairy cow plasma, milk, urine, heart, liver, spleen, lung, and kidney. The established method was extensively validated by determining the linearity (R2 ≥ 0.990), sensitivity (lower limit of quantification, 0.1–0.2 ng mL−1), recovery (75.3–114.1%), precision (RSD ≤ 13.6%), and stability (≥83.0%). Based on the methodological advances, the carry-over of OTA was subsequently studied after oral administration of 30 μg/kg body weight OTA to dairy cows. As revealed, OTA and OTα were detected in urine, with maximal concentrations of 1.8 ng mL−1 and 324.6 ng mL−1, respectively, but not in milk, plasma, or different tissues, verifying the protection effects of rumen flora against OTA exposure for dairy cows. Moreover, 100 fresh milk samples randomly collected from different supermarkets in Shanghai were also analyzed, and no positive samples were found, further proving the correctness of the in vivo biotransformation results. Thus, from the currently available data, regarding OTA contamination issues on dairy cows, no significant health risks were related to OTA exposure due to the consumption of these products.

scholarly journals Xanthohumol, a Prenylated Flavonoid from Hops, Induces DNA Damages in Colorectal Cancer Cells and Sensitizes SW480 Cells to the SN38 Chemotherapeutic Agent

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 932
Author(s):  
Alessandra Scagliarini ◽  
Aline Mathey ◽  
Virginie Aires ◽  
Dominique Delmas
Keyword(s):  
Colorectal Cancer ◽  
Dna Damage ◽  
Anticancer Agents ◽  
Ataxia Telangiectasia Mutated ◽  
Anticancer Compounds ◽  
Dna Damages ◽  
Systematic Screening ◽  
Colorectal Cancer Cells ◽  
Ic50 Values ◽  
First Time

In spite of chemotherapy and systematic screening for people at risk, the mortality rate of colorectal cancer (CRC) remains consistently high, with 600,000 deaths per year. This low success rate in the treatment of CRC results from many failures associated with high resistance and the risk of metastasis. Therefore, in response to these therapeutic failures, new strategies have been under development for several years aimed at increasing the effect of anticancer compounds and/or at reducing their secondary effects on normal cells, thus enabling the host to better withstand chemotherapy. This study highlights that xanthohumol (Xn) concentrations under the IC50 values were able to induce apoptosis and to enhance the DNA-damage response (DDR). We demonstrate for the first time that Xn exerts its anticancer activity in models of colon cancer through activation of the ataxia telangiectasia mutated (ATM) pathway. Subsequently, the ability of Xn to restore DNA damage in CRC cells can sensitize them to anticancer agents such as SN38 (7-ethyl-10-hydroxycamptothecin) used in chemotherapy.

scholarly journals Reflections on communication of disease prognosis and life expectancy by patients with colorectal cancer undergoing palliative care: a qualitative study

BMJ Open ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. e023463 ◽  
Author(s):  
Gudrun Rohde ◽  
Ulrika Söderhamn ◽  
Ingvild Vistad
Keyword(s):  
Colorectal Cancer ◽  
Palliative Care ◽  
Life Expectancy ◽  
Palliative Treatment ◽  
Palliative Chemotherapy ◽  
Qualitative Content Analysis ◽  
Disease Status ◽  
Disease Trajectory ◽  
First Time ◽  
Line Chemotherapy

ObjectivesPatients with colorectal cancer undergoing palliative treatment receive extensive treatment-related information throughout their disease trajectory. We aimed to explore the experiences of patients with incurable colorectal cancer while in palliative care and their reflections on the information provided by physicians and nurses. Our main focus was the patients’ thoughts about how information about disease status and life expectancy was communicated, from the first time that they were informed about the incurable nature of their disease through to postsurgery palliative treatment.SettingsPatients with colorectal cancer receiving palliative chemotherapy.Research designWe used a qualitative approach, and the data were analysed by qualitative content analysis.Participants20 patients (34–75 years of age) were included in the study; 12 received first-line chemotherapy and 8 received second-line chemotherapy. Eleven patients were treated by oncologists, and nine were treated by junior physicians.ResultsData-driven empirical analysis identified three themes: (1) inadequate information during the initial phase of the disease trajectory; (2) hope and information further into the disease trajectory and (3) personal, professional and organisational factors that influenced information and communication throughout the disease trajectory.ConclusionThe participants’ experience of being told for the first time that they had an incurable disease was perceived as inadequate, while postsurgery palliative chemotherapy, physicians and nurses offered hope. The participants preferred customised information about their treatment and likely future prospects and physicians and nurses who took a holistic and compassionate approach focusing on their lifeworld. To be a sensitive, holistic and compassionate physician or nurse requires knowledge and confidence. To achieve this requires training and guidance at universities and in hospitals.

Cost implications of reactive versus prospective testing for dihydropyrimidine dehydrogenase (DPD) deficiency in patients with colorectal cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3627-3627
Author(s):  
Gul Ahmed ◽  
Jo O' Keeffe ◽  
Denise O Mullane ◽  
Alison Bransfield ◽  
Andrew Kenny ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Disease ◽  
Standard Dose ◽  
Dihydropyrimidine Dehydrogenase ◽  
Severe Toxicity ◽  
First Line ◽  
Time Period ◽  
Cost Implications ◽  
The Cost ◽  
First Time

3627 Background: DPD is an enzyme encoded by the DPYD gene involved in the metabolism of the chemotherapy drug 5-fluorouracil (5FU) and the oral 5FU prodrug capecitabine. Patients (pts) with DPYD mutations are at risk of severe toxicities from standard dose 5FU, although they may safely receive lower dose therapy with careful monitoring and dose escalation. Methods: In this retrospective study we identified all pts starting 5FU-based chemotherapy for colorectal cancer (CRC) at our institution between Jan 1 2010 and Dec 31 2012. During this time DPD testing was usually performed in a reactive manner, typically for pts experiencing severe toxicities. We reviewed the charts of pts who tested positive for DPYD mutations and assessed the financial implications of their hospitalizations with toxicity. These costs were compared to the costs which would have incurred if all pts starting such therapy had been proactively tested. Results: A total of 134 pts started first-line 5FU-based chemotherapy for CRC over the study period, 66 in the adjuvant setting and 68 for metastatic disease. 31 pts had DPYD mutation testing performed. 6 tests (19% of those tested, 4.5% of the total population) revealed heterozygote DPYD mutations. 5 pts had already experienced severe treatment-related toxicity resulting in cessation of therapy, while one was tested prospectively and received chemotherapy with dose reduction ab initio. The total cost related to hospitalization with toxicity for these 5 pts was €155,083. At €177 per test, the cost to prospectively test all pts starting first-line 5FU-based therapy over the time period would have been €23,718 representing a saving of €131,365 through avoiding these admissions alone. 4 pts who tested positive for DPYD mutations were receiving adjuvant therapy and none restarted therapy following severe toxicity early in their therapy. 2 pts subsequently relapsed with metastatic disease. Conclusions: Prospective testing for DPYD mutations in pts with CRC starting 5FU-based therapy for the first time represents a considerable cost-saving opportunity, in addition to potentially avoiding prolonged hospitalization and morbidity for a sizeable minority of pts.

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