80 results on '"Bouvier R"'
Search Results
2. Targeting the Metabolic Paradigms in Cancer and Diabetes.
- Author
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Bosso, Mira, Haddad, Dania, Al Madhoun, Ashraf, and Al-Mulla, Fahd
- Subjects
TYPE 2 diabetes ,DIABETES ,LIPOIC acid ,OXIDATIVE phosphorylation ,INSULIN resistance - Abstract
Dysregulated metabolic dynamics are evident in both cancer and diabetes, with metabolic alterations representing a facet of the myriad changes observed in these conditions. This review delves into the commonalities in metabolism between cancer and type 2 diabetes (T2D), focusing specifically on the contrasting roles of oxidative phosphorylation (OXPHOS) and glycolysis as primary energy-generating pathways within cells. Building on earlier research, we explore how a shift towards one pathway over the other serves as a foundational aspect in the development of cancer and T2D. Unlike previous reviews, we posit that this shift may occur in seemingly opposing yet complementary directions, akin to the Yin and Yang concept. These metabolic fluctuations reveal an intricate network of underlying defective signaling pathways, orchestrating the pathogenesis and progression of each disease. The Warburg phenomenon, characterized by the prevalence of aerobic glycolysis over minimal to no OXPHOS, emerges as the predominant metabolic phenotype in cancer. Conversely, in T2D, the prevailing metabolic paradigm has traditionally been perceived in terms of discrete irregularities rather than an OXPHOS-to-glycolysis shift. Throughout T2D pathogenesis, OXPHOS remains consistently heightened due to chronic hyperglycemia or hyperinsulinemia. In advanced insulin resistance and T2D, the metabolic landscape becomes more complex, featuring differential tissue-specific alterations that affect OXPHOS. Recent findings suggest that addressing the metabolic imbalance in both cancer and diabetes could offer an effective treatment strategy. Numerous pharmaceutical and nutritional modalities exhibiting therapeutic effects in both conditions ultimately modulate the OXPHOS–glycolysis axis. Noteworthy nutritional adjuncts, such as alpha-lipoic acid, flavonoids, and glutamine, demonstrate the ability to reprogram metabolism, exerting anti-tumor and anti-diabetic effects. Similarly, pharmacological agents like metformin exhibit therapeutic efficacy in both T2D and cancer. This review discusses the molecular mechanisms underlying these metabolic shifts and explores promising therapeutic strategies aimed at reversing the metabolic imbalance in both disease scenarios. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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3. Investigation and comparison of laser and ultrasound effects on the temperature increasing of the solutions containing graphene oxide nanoparticles for thermal treatment of osteosarcoma cancer cells.
- Author
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Hosseini Motlagh, Najmeh Sadat, Sharifi, Elyas, Hghiralsadat, Bibi Fatemeh, Zarchi, Mohsen Sardari, Yaghoubi, Fatemeh, and Oroojalian, Fatemeh
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LASER ultrasonics ,PHOTOTHERMAL effect ,TEMPERATURE effect ,CANCER cells ,LASER beams ,CANCER treatment - Abstract
Objective(s): The waves of ultrasound and laser in the presence of nanoparticles are introduced as desirable candidates for the thermal treatment of cancer due to having fewer side effects, more speed, and superior treatment efficiency. Here, 2D Graphene oxide nanoparticle is used as a thermal nano-convertor for increasing the yield of thermal cancer therapy. Materials and Methods: The temperature of GO (in 0.2 and 0.4 mg/ml concentrations) and deionized water regarding heater, bath sonicate, probe sonicate (at a power range of 2-3.5 W), and laser properties at 808 nm with continuous wave (at a power of 0-2 W) in 10 min are investigated. Based on the experimental results, the effect of laser and ultrasound radiation on the temperature is simulated using a data mining approach. Results: Experimental and simulation results show that GO nanoparticle in this form is unsuitable for converting ultrasound waves into heat. But it is a strong absorber for electromagnetic waves at 808 nm and can raise the temperature to 85 °C. The results indicate that the laser + GO enhances the mortality percentage and treatment yield of MG63 cancerous cells by up to 85%. Also, GO uptake is analyzed by fluorescent microscopic images. Conclusion: This analysis confirmed that GO is important when laser radiation is used but not when Ultrasound is employed. Also, GO is an excellent photothermal nanoparticle for localized thermal therapy of osteosarcoma cancer cells by laser at 808 nm with low side effects. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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4. Correlation of serum prostate specific antigen and semi quantitative tissue RT-PCR from prostate cancer samples.
- Author
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Colombel, M, Marechal, J M, Gelet, A, Pangaud, C, Bouvier, R, Martin, X, Dubernard, J M, and Lasne, Y
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PROSTATE cancer ,CANCER - Abstract
Serum PSA level is associated with peri operative and pathological prognostic indicators. Although there is a statistically significant relationship between serum PSA level and tumour extent, in cases of the same tumour volume or grade, serum PSA levels range from less than 4 ng/ml to more than 10 ng/ml. Previous immuno histochemical studies from human prostate cancer samples have failed to explain the variability of PSA production. The objective of our study was to assess the relationship between the level of tissue PSA RNA from normal and prostate cancer biopsies and the level of PSA. [ABSTRACT FROM AUTHOR]
- Published
- 2000
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5. Mitochondrial respiratory complexes: Significance in human mitochondrial disorders and cancers.
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Vikramdeo, Kunwar Somesh, Sudan, Sarabjeet Kour, Singh, Ajay P., Singh, Seema, and Dasgupta, Santanu
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MITOCHONDRIAL pathology ,OXIDATIVE phosphorylation ,MITOCHONDRIA ,CELLULAR signal transduction ,ORGANELLES ,HOMEOSTASIS - Abstract
Mitochondria are pivotal organelles that govern cellular energy production through the oxidative phosphorylation system utilizing five respiratory complexes. In addition, mitochondria also contribute to various critical signaling pathways including apoptosis, damage‐associated molecular patterns, calcium homeostasis, lipid, and amino acid biosynthesis. Among these diverse functions, the energy generation program oversee by mitochondria represents an immaculate orchestration and functional coordination between the mitochondria and nuclear encoded molecules. Perturbation in this program through respiratory complexes' alteration results in the manifestation of various mitochondrial disorders and malignancy, which is alarmingly becoming evident in the recent literature. Considering the clinical relevance and importance of this emerging medical problem, this review sheds light on the timing and nature of molecular alterations in various respiratory complexes and their functional consequences observed in various mitochondrial disorders and human cancers. Finally, we discussed how this wealth of information could be exploited and tailored to develop respiratory complex targeted personalized therapeutics and biomarkers for better management of various incurable human mitochondrial disorders and cancers. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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6. Applications of Focused Ultrasound in the Treatment of Genitourinary Cancers.
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Panzone, John, Byler, Timothy, Bratslavsky, Gennady, and Goldberg, Hanan
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BLADDER tumors ,EVALUATION of medical care ,PENILE tumors ,GENITOURINARY organ tumors ,KIDNEY tumors ,TESTIS tumors ,ULTRASONIC therapy ,PROSTATE tumors - Abstract
Simple Summary: Cancer is a prevalent disease globally, and conventional treatment options have been associated with substantial morbidity for patients. The unique acoustic properties and biological effects of focused ultrasound have been investigated for use as an alternative treatment option for various forms of cancer with lower associated morbidity than standard treatments. The objective of our review was to assess the current state and various applications of focused ultrasound for the treatment of genitourinary cancers, including prostate, kidney, bladder, penile, and testicular malignancies. Current research demonstrates that focused ultrasound-based focal therapy shows promise for the treatment of localized prostate and kidney cancer, and the effect of ultrasound on cell membranes may increase the efficacy of chemotherapeutics and radiotherapy. Focused ultrasound-based treatment modalities should continue to be investigated as an alternative or complementary treatment option for cancer patients. Traditional cancer treatments have been associated with substantial morbidity for patients. Focused ultrasound offers a novel modality for the treatment of various forms of cancer which may offer effective oncological control and low morbidity. We performed a review of PubMed articles assessing the current applications of focused ultrasound in the treatment of genitourinary cancers, including prostate, kidney, bladder, penile, and testicular cancer. Current research indicates that high-intensity focused ultrasound (HIFU) focal therapy offers effective short-term oncologic control of localized prostate and kidney cancer with lower associated morbidity than radical surgery. In addition, studies in mice have demonstrated that focused ultrasound treatment increases the accuracy of chemotherapeutic drug delivery, the efficacy of drug uptake, and cytotoxic effects within targeted cancer cells. Ultrasound-based therapy shows promise for the treatment of genitourinary cancers. Further research should continue to investigate focused ultrasound as an alternative cancer treatment option or as a complement to increase the efficacy of conventional treatments such as chemotherapy and radiotherapy. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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7. Malignancies after pediatric solid organ transplantation.
- Author
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Robinson, Cal, Chanchlani, Rahul, and Kitchlu, Abhijat
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TUMOR risk factors ,TIME ,PEDIATRICS ,RISK assessment ,SKIN tumors ,TUMORS in children ,LYMPHOPROLIFERATIVE disorders ,TRANSPLANTATION of organs, tissues, etc. ,DISEASE risk factors - Abstract
As life expectancy among pediatric solid organ transplant recipients (SOTRs) improves, the risk of comorbid conditions such as malignancy post-transplantation has also increased. SOTRs are at elevated risks of post-transplantation lymphoproliferative disorders (PTLDs), and skin and solid cancers. PTLDs typically occur early following transplantation, while skin and solid cancers frequently arise in young adulthood (25–40 years). By 30 years following transplantation, 26–41% of pediatric SOTRs have developed cancer. Different risk factors exist for PTLD, and skin and solid cancers, which are modified by cumulative immunosuppression, infections, transplanted organ, and the underlying disease process associated with initial organ failure (e.g., kidney failure). Optimal cancer treatment strategies depend on the specific cancer type, stage, and patient comorbidities. Immunosuppression reduction may be beneficial for certain cancers but must be considered against the risks of acute and chronic rejection and allograft loss. Lifestyle counseling regarding smoking avoidance and sun protection, as well as human papillomavirus vaccination, is an important aspect of cancer prevention. Currently, no cancer screening guidelines exist specifically for pediatric SOTRs. Adult population screening guidelines have not been validated in transplant populations. Therefore, an individualized approach should be taken to cancer screening for pediatric SOTRs, accounting for other cancer risk factors. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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8. THE FGF/FGFR SYSTEM IN THE PHYSIOPATHOLOGY OF THE PROSTATE GLAND.
- Author
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Giacomini, Arianna, Grillo, Elisabetta, Rezzola, Sara, Ribatti, Domenico, Rusnati, Marco, Ronca, Roberto, and Presta, Marco
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Fibroblast growth factors (FGFs) are a family of proteins possessing paracrine, autocrine, or endocrine functions in a variety of biological processes, including embryonic development, angiogenesis, tissue homeostasis, wound repair, and cancer. Canonical FGFs bind and activate tyrosine kinase FGF receptors (FGFRs), triggering intracellular signaling cascades that mediate their biological activity. Experimental evidence indicates that FGFs play a complex role in the physiopathology of the prostate gland that ranges from essential functions during embryonic development to modulation of neoplastic transformation. The use of ligand- and receptor-deleted mouse models has highlighted the requirement for FGF signaling in the normal development of the prostate gland. In adult prostate, the maintenance of a functional FGF/FGFR signaling axis is critical for organ homeostasis and function, as its disruption leads to prostate hyperplasia and may contribute to cancer progression and metastatic dissemination. Dissection of the molecular landscape modulated by the FGF family will facilitate ongoing translational efforts directed toward prostate cancer therapy. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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9. Cancer morbidity and mortality after pediatric solid organ transplantation—a nationwide register study.
- Author
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Endén, Kira, Tainio, Juuso, Nikkilä, Atte, Helanterä, Ilkka, Nordin, Arno, Pakarinen, Mikko P, Jalanko, Hannu, Jahnukainen, Kirsi, and Jahnukainen, Timo
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DISEASE risk factors ,MORTALITY risk factors ,COMPARATIVE studies ,CONFIDENCE intervals ,HEART transplantation ,KIDNEY transplantation ,LIVER transplantation ,RISK assessment ,TRANSPLANTATION of organs, tissues, etc. ,TUMORS ,DESCRIPTIVE statistics - Abstract
Background: The prevalence of malignancies after pediatric solid organ transplantation was evaluated in a nationwide study. Methods: All patients who had undergone kidney, liver, or heart transplantation during childhood between the years 1982 and 2015 in Finland were identified. The inclusion criteria were age under 16 years at transplantation and age over 18 years at the last follow-up day. A total of 233 (137 kidney, 53 liver, and 43 heart) transplant recipients were enrolled. Controls (n = 1157) matched by the year of birth, gender, and hometown were identified using the Population Register Center registry. The cancer diagnoses were searched using the Finnish Cancer Registry. Results: Altogether 26 individuals diagnosed with cancer were found, including 18 transplant recipients. Cancer was diagnosed at a median of 12.0 (IQR 7.8–17.8) years after the transplantation. The transplant recipients' risk for cancer was significantly higher when compared with the controls (HR 14.7; 95% CI 6.4–33.9). There was no difference for different graft types. Sixty-one percent of cancers among the transplant recipients were diagnosed at age older than 18 years. Conclusion: The risk for cancer is significantly higher among young adults having undergone solid organ transplantation during childhood in comparison with population controls. Careful follow-up and attention to prevent cancers throughout adulthood are warranted. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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10. MicroRNAs as Urinary Biomarker for Oncocytoma.
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von Brandenstein, Melanie, Schlosser, Monika, Herden, Jan, Heidenreich, Axel, Störkel, Stefan, and Fries, Jochen W. U.
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MICRORNA ,BIOLOGICAL tags ,BENIGN tumors ,CANCER ,IMMUNOHISTOCHEMISTRY - Abstract
The identification of benign renal oncocytoma, its differentiation from malignant renal tumors, and their eosinophilic variants are a continuous challenge, influencing preoperative planning and being an unnecessary stress factor for patients. Regressive changes enhance the diagnostic dilemma, making evaluations by frozen sections or by immunohistology (on biopsies) unreliable. MicroRNAs (miRs) have been proposed as novel biomarkers to differentiate renal tumor subtypes. However, their value as a diagnostic biomarker of oncocytoma in urines based on mechanisms known in oncocytomas has not been exploited. We used urines from patients with renal tumors (oncocytoma, renal cell carcinoma: clear cell, papillary, chromophobe) and with other urogenital lesions. miRs were extracted and detected via qRT-PCR, the respective tumors analyzed by immunohistology. We found isocitrate dehydrogenase 2 upregulated in oncocytoma and oncocytic chromophobe carcinoma, indicating an increased Krebs cycle metabolism. Since we had shown that all renal tumors are stimulated by endothelin-1, we analyzed miRs preidentified by microarray after endothelin-1 stimulation of renal epithelial cells. Four miRs are proposed as presurgical urinary biomarkers due to their known regulatory mechanism in oncocytoma: miR-498 (formation of the oncocytoma-specific slice-form of vimentin, Vim3), miR-183 (associated with increased CO
2 levels), miR-205, and miR-31 (signaling through downregulation of PKC epsilon, shown previously). [ABSTRACT FROM AUTHOR]- Published
- 2018
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11. A Comprehensive Review of Pediatric Tumors and Associated Cancer Predisposition Syndromes.
- Author
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Scollon, Sarah, Anglin, Amanda, Thomas, Martha, Turner, Joyce, and Wolfe Schneider, Kami
- Abstract
An understanding of the role of inherited cancer predisposition syndromes in pediatric tumor diagnoses continues to develop as more information is learned through the application of genomic technology. Identifying patients and their relatives at an increased risk for developing cancer is an important step in the care of this patient population. The purpose of this review is to highlight various tumor types that arise in the pediatric population and the cancer predisposition syndromes associated with those tumors. The review serves as a guide for recognizing genes and conditions to consider when a pediatric cancer referral presents to the genetics clinic. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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12. Activins in reproductive biology and beyond.
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Wijayarathna, R. and de Kretser, D. M.
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ACTIVIN ,HUMAN reproduction ,TRANSFORMING growth factors-beta ,GENITALIA development ,TREATMENT of female reproductive organ diseases ,DEVELOPMENTAL biology ,GENETIC overexpression ,OVARIAN physiology ,TESTIS physiology ,CARRIER proteins ,GLYCOPROTEINS ,OVARIAN tumors ,PEPTIDE hormones ,PREECLAMPSIA ,SYSTEMATIC reviews - Abstract
Background: Activins are members of the pleiotrophic family of the transforming growth factor-beta (TGF-β) superfamily of cytokines, initially isolated for their capacity to induce the release of FSH from pituitary extracts. Subsequent research has demonstrated that activins are involved in multiple biological functions including the control of inflammation, fibrosis, developmental biology and tumourigenesis. This review summarizes the current knowledge on the roles of activin in reproductive and developmental biology. It also discusses interesting advances in the field of modulating the bioactivity of activins as a therapeutic target, which would undoubtedly be beneficial for patients with reproductive pathology.Methods: A comprehensive literature search was carried out using PUBMED and Google Scholar databases to identify studies in the English language which have contributed to the advancement of the field of activin biology, since its initial isolation in 1987 until July 2015. 'Activin', 'testis', 'ovary', 'embryonic development' and 'therapeutic targets' were used as the keywords in combination with other search phrases relevant to the topic of activin biology.Results: Activins, which are dimers of inhibin β subunits, act via a classical TGF-β signalling pathway. The bioactivity of activin is regulated by two endogenous inhibitors, inhibin and follistatin. Activin is a major regulator of testicular and ovarian development. In the ovary, activin A promotes oocyte maturation and regulates granulosa cell steroidogenesis. It is also essential in endometrial repair following menstruation, decidualization and maintaining pregnancy. Dysregulation of the activin-follistatin-inhibin system leads to disorders of female reproduction and pregnancy, including polycystic ovary syndrome, ectopic pregnancy, miscarriage, fetal growth restriction, gestational diabetes, pre-eclampsia and pre-term birth. Moreover, a rise in serum activin A, accompanied by elevated FSH, is characteristic of female reproductive aging. In the male, activin A is an autocrine and paracrine modulator of germ cell development and Sertoli cell proliferation. Disruption of normal activin signalling is characteristic of many tumours affecting reproductive organs, including endometrial carcinoma, cervical cancer, testicular and ovarian cancer as well as prostate cancer. While activin A and B aid the progression of many tumours of the reproductive organs, activin C acts as a tumour suppressor. Activins are important in embryonic induction, morphogenesis of branched glandular organs, development of limbs and nervous system, craniofacial and dental development and morphogenesis of the Wolffian duct.Conclusions: The field of activin biology has advanced considerably since its initial discovery as an FSH stimulating agent. Now, activin is well known as a growth factor and cytokine that regulates many aspects of reproductive biology, developmental biology and also inflammation and immunological mechanisms. Current research provides evidence for novel roles of activins in maintaining the structure and function of reproductive and other organ systems. The fact that activin A is elevated both locally as well as systemically in major disorders of the reproductive system makes it an important biomarker. Given the established role of activin A as a pro-inflammatory and pro-fibrotic agent, studies of its involvement in disorders of reproduction resulting from these processes should be examined. Follistatin, as a key regulator of the biological actions of activin, should be evaluated as a therapeutic agent in conditions where activin A overexpression is established as a contributing factor. [ABSTRACT FROM AUTHOR]- Published
- 2016
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13. miR-30a-5p in the tumorigenesis of renal cell carcinoma: A tumor suppressive microRNA.
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YIFAN LI, YUCHI LI, DUQUN CHEN, LU JIN, ZHENGMING SU, JIAJU LIU, HONGFANG DUAN, XIAOQING LI, ZHENGYU QI, MIN SHI, LIANGCHAO NI, SHANGQI YANG, YAOTING GUI, XIANGMING MAO, YUN CHEN, and YONGQING LAI
- Subjects
RENAL cell carcinoma ,CANCER ,KIDNEY diseases ,MICRORNA ,CELL proliferation - Abstract
Renal cell carcinoma (RCC) is the most common type of malignant tumor of the adult kidney and has a poor prognosis. MicroRNAs (miRs) are important in a wide range of biological and pathological processes, including cell differentiation, migration, growth, proliferation, apoptosis and metabolism. The present study aimed to determine the role exerted by miR-30a-5p in the tumorigenesis of RCC. The expression levels of miR-30a-5p in RCC tissues and RCC-derived cells were demonstrated to be significantly downregulated by real-time quantitative polymerase chain reaction (RT-qPCR). Wound scratch assay, cell proliferation assay and flow cytometric analysis revealed that the abilities of migration and proliferation of the RCC-derived cells were suppressed, whereas cell apoptosis was promoted, when miR-30a-5p was overexpressed in these cells. N-acetylgalactos aminyltransferase 7 (GALNT7) was predicted to be one target gene of miR-30a-5p by bioinformatics analysis. Luciferase reporter assay, RT-qPCR and western blotting were performed to confirm that GALNT7 is the direct conserved target of miR-30a-5p. These results suggested that miR-30a-5p has a tumor-suppressive role in the tumorigenesis of RCC. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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14. Oncostatic-Cytoprotective Effect of Melatonin and Other Bioactive Molecules: A Common Target in Mitochondrial Respiration.
- Author
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Pacini, Nicola and Borziani, Fabio
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MELATONIN ,MOLECULES ,MITOCHONDRIA ,NEURODEGENERATION ,GLYCOLYSIS ,OXIDATIVE phosphorylation - Abstract
For several years, oncostatic and antiproliferative properties, as well as thoses of cell death induction through 5-methoxy-N-acetiltryptamine or melatonin treatment, have been known. Paradoxically, its remarkable scavenger, cytoprotective and anti-apoptotic characteristics in neurodegeneration models, such as Alzheimer's disease and Parkinson's disease are known too. Analogous results have been confirmed by a large literature to be associated to the use of many other bioactive molecules such as resveratrol, tocopherol derivatives or vitamin E and others. It is interesting to note that the two opposite situations, namely the neoplastic pathology and the neurodegeneration, are characterized by deep alterations of the metabolome, of mitochondrial function and of oxygen consumption, so that the oncostatic and cytoprotective action can find a potential rationalization because of the different metabolic and mitochondrial situations, and in the effect that these molecules exercise on the mitochondrial function. In this review we discuss historical and general aspects of melatonin, relations between cancers and the metabolome and between neurodegeneration and the metabolome, and the possible effects of melatonin and of other bioactive molecules on metabolic and mitochondrial dynamics. Finally, we suggest a common general mechanism as responsible for the oncostatic/cytoprotective effect of melatonin and of other molecules examined. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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15. MRI Methods for the Evaluation of High Intensity Focused Ultrasound Tumor Treatment: Current Status and Future Needs.
- Author
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Hectors, Stefanie J.C.G., Jacobs, Igor, Moonen, Chrit T.W., Strijkers, Gustav J., and Nicolay, Klaas
- Abstract
Thermal ablation with high intensity focused ultrasound (HIFU) is an emerging noninvasive technique for the treatment of solid tumors. HIFU treatment of malignant tumors requires accurate treatment planning, monitoring and evaluation, which can be facilitated by performing the procedure in an MR-guided HIFU system. The MR-based evaluation of HIFU treatment is most often restricted to contrast-enhanced T
1 -weighted imaging, while it has been shown that the non-perfused volume may not reflect the extent of nonviable tumor tissue after HIFU treatment. There are multiple studies in which more advanced MRI methods were assessed for their suitability for the evaluation of HIFU treatment. While several of these methods seem promising regarding their sensitivity to HIFU-induced tissue changes, there is still ample room for improvement of MRI protocols for HIFU treatment evaluation. In this review article, we describe the major acute and delayed effects of HIFU treatment. For each effect, the MRI methods that have been- or could be-used to detect the associated tissue changes are described. In addition, the potential value of multiparametric MRI for the evaluation of HIFU treatment is discussed. The review ends with a discussion on future directions for the MRI-based evaluation of HIFU treatment. [ABSTRACT FROM AUTHOR]- Published
- 2016
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16. Malignant neuroendocrine tumour of the appendix in childhood with loco-regional lymph node invasion.
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Lyons, Rebecca F., Irfan, Muhammad, Waldron, Ronan, Bambury, Niamh, Bennani, Fadel, Nemeth, Tamas, Khan, Waqar, and Barry, Kevin
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NEUROENDOCRINE tumors ,APPENDIX (Anatomy) ,CHILDHOOD cancer ,LYMPH nodes ,PATHOLOGY ,CANCER - Abstract
Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/ 1006600359152743 [ABSTRACT FROM AUTHOR]
- Published
- 2015
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17. Targeting Carbonic Anhydrase IX Activity and Expression.
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Mahon, Brian P., Pinard, Melissa A., and McKenna, Robert
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CARBONIC anhydrase ,CELL proliferation ,TUMOR growth ,RNA interference ,GENE expression ,ANTINEOPLASTIC agents - Abstract
Metastatic tumors are often hypoxic exhibiting a decrease in extracellular pH (~6.5) due to a metabolic transition described by the Warburg Effect. This shift in tumor cell metabolism alters the tumor milieu inducing tumor cell proliferation, angiogenesis, cell motility, invasiveness, and often resistance to common anti-cancer treatments; hence hindering treatment of aggressive cancers. As a result, tumors exhibiting this phenotype are directly associated with poor prognosis and decreased survival rates in cancer patients. A key component to this tumor microenvironment is carbonic anhydrase IX (CA IX). Knockdown of CA IX expression or inhibition of its activity has been shown to reduce primary tumor growth, tumor proliferation, and also decrease tumor resistance to conventional anti-cancer therapies. As such several approaches have been taken to target CA IX in tumors via small-molecule, anti-body, and RNAi delivery systems. Here we will review recent developments that have exploited these approaches and provide our thoughts for future directions of CA IX targeting for the treatment of cancer. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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18. 3D conformal MRI-guided transurethral ultrasound therapy: results of gel phantom experiments.
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N'Djin, W. A., Burtnyk, M., McCormick, S., Bronskill, M., and Chopra, R.
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PROSTATE cancer treatment ,TRANSURETHRAL prostatectomy ,DIAGNOSTIC ultrasonic imaging ,MEDICAL imaging systems ,THREE-dimensional imaging ,MAGNETIC resonance imaging ,MEDICAL thermometry - Abstract
MRI-guided transurethral ultrasound therapy shows promise for minimally invasive treatment of localized prostate cancer. Previous in-vivo studies demonstrated the feasibility of performing conservative treatments using real-time temperature feedback to control accurately the establishment of coagulative lesions within circumscribed prostate regions. This in-vitro study tested device configuration and control options for achieving full prostate treatments. A multi-channel MRI compatible ultrasound therapy system was evaluated in gel phantoms using 3 canine prostate models. Prostate profiles were 5mm-step-segmented from T2-weighted MR images performed during previous in-vivo experiments. During ultrasound exposures, each ultrasound element was controlled independently by the 3D controller. Decisions on acoustic power, frequency, and device rotation rate were made in real time based on MR thermometry feedback and prostate radii. Low and high power treatment approaches using maximum acoustic powers of 10 or 20 W.cm-2 were tested as well as single and dual-frequency strategies (4.05/13.10 MHz). The dual-frequency strategy used either the fundamental frequency or the 3rd harmonic component, depending on the prostate radius. The 20 W.cm-2 dual frequency approach was the most efficient configuration in achieving full prostate treatments. Treatment times were about half the duration of those performed with 10 W.cm-2 configurations. Full prostate coagulations were performed in 16.3 ± 6.1 min at a rate of 1.8 ± 0.2 cm3.min-1, and resulted in very little undertreated tissue (< 3%). Surrounding organs positioned beyond a safety distance of 1.4 ± 1.0 mm from prostate boundaries were not damaged, particularly rectal wall tissues. In this study, a 3D, MR-thermometry-guided transurethral ultrasound therapy was validated in vitro in a tissue-mimicking phantom for performing full prostate treatment. A dualfrequency configuration with 20 W.cm-2 ultrasound intensity exposure showed good results with direct application to full human prostate treatments. [ABSTRACT FROM AUTHOR]
- Published
- 2011
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19. Microbiota and mitobiota. Putting an equal sign between mitochondria and bacteria.
- Author
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Zorov, D., Plotnikov, E., Silachev, D., Zorova, L., Pevzner, I., Zorov, S., Babenko, V., Jankauskas, S., Popkov, V., and Savina, P.
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BIOTIC communities ,MITOCHONDRIAL physiology ,BACTERIAL diseases ,HOMEOSTASIS ,GENOMICS ,COMPARATIVE studies - Abstract
The recent revival of old theories and setting them on modern scientific rails to a large extent are also relevant to mitochondrial science. Given the widespread belief that mitochondria are symbionts of ancient bacterial origin, the processes inherent to mitochondrial physiology can be revised based on their comparative analysis with possible involvement of bacteria. Such comparison combined with discussion of the role of microbiota in pathogenesis allows discussion of the role of 'mitobiota' (we introduce this term) as the combination of different phenotypic manifestations of mitochondria in the organism reflecting pathological changes in the mitochondrial genome. When putting an equal sign between mitochondria and bacteria, we find similarity between the mitochondrial and bacterial theories of cancer. The presence of the term 'bacterial infection' suggests 'mitochondrial infection', and mitochondrial (oxidative) theory of aging can in some way be transformed into a 'bacterial theory of aging'. The possible existence of such processes and the data confirming their presence are discussed in this review. If such a comparison has the right to exist, the homeostasis of 'mitobiota' is of not lesser physiological importance than homeostasis of microbiota, which has been so intensively discussed recently. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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20. Malignancies after pediatric kidney transplantation: more than PTLD?
- Author
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Mynarek, Martin, Hussein, Kais, Kreipe, Hans, and Maecker-Kolhoff, Britta
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BASAL cell carcinoma ,SQUAMOUS cell carcinoma ,TUMOR prevention ,TUMORS in children ,LUNG tumors ,STOMACH tumors ,LIVER tumors ,KIDNEY tumors ,EPSTEIN-Barr virus ,IMMUNIZATION ,IMMUNOSUPPRESSION ,IMMUNOSUPPRESSIVE agents ,KAPOSI'S sarcoma ,KIDNEY transplantation ,EARLY detection of cancer ,CHILDREN ,LYMPHOPROLIFERATIVE disorders ,PROGNOSIS ,CANCER risk factors ,DISEASE risk factors ,TUMOR risk factors - Abstract
Post-transplant lymphoproliferative disease (PTLD) is the most frequent malignant complication of transplantation in childhood. Even with modern post-transplant immunosuppressive strategies, 1-2 % of all kidney transplant recipients will develop PTLD within the first 5 years after transplantation, and the risk remains high even thereafter as long as immunosuppression is required. In addition to PTLD, adult kidney transplant recipients have an increased incidence of other immunosuppression-related malignancies, such as non-melanoma skin cancer or Kaposi's sarcoma. It is foreseeable that pediatric transplant recipients will face similar complications during their adult life. Not only immunosuppression but also other risk factors have been identified for some of these malignancies. Strategies addressing these risk factors during childhood may contribute to life-long cancer prevention. Furthermore, early recognition and regular screening may facilitate early diagnosis and treatment, thereby reducing transplant-related morbidity. In this review we focus on malignant complications after renal transplantation and discuss known risk factors. We also review current screening strategies for malignancies during post-transplant follow-up. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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21. Cancer Stem Cell Theory and the Warburg Effect, Two Sides of the Same Coin?
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Pacini, Nicola and Borziani, Fabio
- Subjects
HISTOPATHOLOGY ,TUMORS ,CANCER stem cells ,EPIGENETICS ,GENETIC mutation ,NEOPLASTIC cell transformation - Abstract
Over the last 100 years, many studies have been performed to determine the biochemical and histopathological phenomena that mark the origin of neoplasms. At the end of the last century, the leading paradigm, which is currently well rooted, considered the origin of neoplasms to be a set of genetic and/or epigenetic mutations, stochastic and independent in a single cell, or rather, a stochastic monoclonal pattern. However, in the last 20 years, two important areas of research have underlined numerous limitations and incongruities of this pattern, the hypothesis of the so-called cancer stem cell theory and a revaluation of several alterations in metabolic networks that are typical of the neoplastic cell, the so-called Warburg effect. Even if this specific "metabolic sign" has been known for more than 85 years, only in the last few years has it been given more attention; therefore, the so-called Warburg hypothesis has been used in multiple and independent surveys. Based on an accurate analysis of a series of considerations and of biophysical thermodynamic events in the literature, we will demonstrate a homogeneous pattern of the cancer stem cell theory, of the Warburg hypothesis and of the stochastic monoclonal pattern; this pattern could contribute considerably as the first basis of the development of a new uniform theory on the origin of neoplasms. Thus, a new possible epistemological paradigm is represented; this paradigm considers the Warburg effect as a specific "metabolic sign" reflecting the stem origin of the neoplastic cell, where, in this specific metabolic order, an essential reason for the genetic instability that is intrinsic to the neoplastic cell is defined. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
22. The Interplay of Hypoxia Signaling on Mitochondrial Dysfunction and Inflammation in Cardiovascular Diseases and Cancer: From Molecular Mechanisms to Therapeutic Approaches.
- Author
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Bouhamida, Esmaa, Morciano, Giampaolo, Perrone, Mariasole, Kahsay, Asrat E., Della Sala, Mario, Wieckowski, Mariusz R., Fiorica, Francesco, Pinton, Paolo, Giorgi, Carlotta, and Patergnani, Simone
- Subjects
CARDIOVASCULAR diseases ,THERAPEUTICS ,HYPOXIA-inducible factor 1 ,HYPOXEMIA ,REACTIVE oxygen species - Abstract
Simple Summary: The regulation of hypoxia has recently emerged as having a central impact in mitochondrial function and dysfunction in various diseases, including the major disorders threatening worldwide: cardiovascular diseases and cancer. Despite the studies in this matter, its effective role in protection and disease progression even though its direct molecular mechanism in both disorders is still to be elucidated. This review aims to cover the current knowledge about the effect of hypoxia on mitochondrial function and dysfunction, and inflammation, in cardiovascular diseases and cancer, and reports further therapeutic strategies based on the modulation of hypoxic pathways. Cardiovascular diseases (CVDs) and cancer continue to be the primary cause of mortality worldwide and their pathomechanisms are a complex and multifactorial process. Insufficient oxygen availability (hypoxia) plays critical roles in the pathogenesis of both CVDs and cancer diseases, and hypoxia-inducible factor 1 (HIF-1), the main sensor of hypoxia, acts as a central regulator of multiple target genes in the human body. Accumulating evidence demonstrates that mitochondria are the major target of hypoxic injury, the most common source of reactive oxygen species during hypoxia and key elements for inflammation regulation during the development of both CVDs and cancer. Taken together, observations propose that hypoxia, mitochondrial abnormality, oxidative stress, inflammation in CVDs, and cancer are closely linked. Based upon these facts, this review aims to deeply discuss these intimate relationships and to summarize current significant findings corroborating the molecular mechanisms and potential therapies involved in hypoxia and mitochondrial dysfunction in CVDs and cancer. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
23. MR-guided focused ultrasound surgery, present and future.
- Author
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Schlesinger, David, Benedict, Stanley, Diederich, Chris, Gedroyc, Wladyslaw, Klibanov, Alexander, and Larner, James
- Subjects
MAGNETIC resonance imaging ,ULTRASONIC imaging ,ONCOLOGY ,RADIOSURGERY ,UTERINE fibroids ,CLINICAL trials - Abstract
MR-guided focused ultrasound surgery (MRgFUS) is a quickly developing technology with potential applications across a spectrum of indications traditionally within the domain of radiation oncology. Especially for applications where focal treatment is the preferred technique (for example, radiosurgery), MRgFUS has the potential to be a disruptive technology that could shift traditional patterns of care. While currently cleared in the United States for the noninvasive treatment of uterine fibroids and bone metastases, a wide range of clinical trials are currently underway, and the number of publications describing advances in MRgFUS is increasing. However, for MRgFUS to make the transition from a research curiosity to a clinical standard of care, a variety of challenges, technical, financial, clinical, and practical, must be overcome. This installment of the Vision 20/20 series examines the current status of MRgFUS, focusing on the hurdles the technology faces before it can cross over from a research technique to a standard fixture in the clinic. It then reviews current and near-term technical developments which may overcome these hurdles and allow MRgFUS to break through into clinical practice. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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- View/download PDF
24. Breakpoint Analysis of Transcriptional and Genomic Profiles Uncovers Novel Gene Fusions Spanning Multiple Human Cancer Types.
- Author
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Giacomini, Craig P., Sun, Steven, Varma, Sushama, Shain, A. Hunter, Giacomini, Marilyn M., Balagtas, Jay, Sweeney, Robert T., Lai, Everett, Vecchio, Catherine A. Del, Forster, Andrew D., Clarke, Nicole, Montgomery, Kelli D., Zhu, Shirley, Wong, Albert J., van de Rijn, Matt, West, Robert B., and Pollack, Jonathan R.
- Subjects
GENE fusion ,GENOMICS ,CANCER ,LEUKEMIA ,GLUTAMIC acid - Abstract
Gene fusions, like BCR/ABL1 in chronic myelogenous leukemia, have long been recognized in hematologic and mesenchymal malignancies. The recent finding of gene fusions in prostate and lung cancers has motivated the search for pathogenic gene fusions in other malignancies. Here, we developed a "breakpoint analysis" pipeline to discover candidate gene fusions by tell-tale transcript level or genomic DNA copy number transitions occurring within genes. Mining data from 974 diverse cancer samples, we identified 198 candidate fusions involving annotated cancer genes. From these, we validated and further characterized novel gene fusions involving ROS1 tyrosine kinase in angiosarcoma (CEP85L/ROS1), SLC1A2 glutamate transporter in colon cancer (APIP/SLC1A2), RAF1 kinase in pancreatic cancer (ATG7/RAF1) and anaplastic astrocytoma (BCL6/RAF1), EWSR1 in melanoma (EWSR1/CREM), CDK6 kinase in T-cell acute lymphoblastic leukemia (FAM133B/ CDK6), and CLTC in breast cancer (CLTC/VMP1). Notably, while these fusions involved known cancer genes, all occurred with novel fusion partners and in previously unreported cancer types. Moreover, several constituted druggable targets (including kinases), with therapeutic implications for their respective malignancies. Lastly, breakpoint analysis identified new cell line models for known rearrangements, including EGFRvIII and FIP1L1/PDGFRA. Taken together, we provide a robust approach for gene fusion discovery, and our results highlight a more widespread role of fusion genes in cancer pathogenesis. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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- View/download PDF
25. Posterior urethral complications of the treatment of prostate cancer.
- Author
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Mundy, Anthony R. and Andrich, Daniela E.
- Subjects
PROSTATE cancer treatment ,THERAPEUTIC complications ,RADIOTHERAPY complications ,URETHRA diseases ,ENDOSCOPY - Abstract
What's known on the subject? and What does the study add? Urethral strictures, bladder neck and posterior urethral contractures, and urorectal fistulation are three well-recognised complications of the treatment of prostate cancer, whether by surgery or non-surgical treatment. Because these are relatively rare problems the treatment is uncertain. There is a heavy reliance on endoscopic or instrumental management of urethral strictures and of bladder neck and posterior urethral contractures, and there is little discrimination in any of these conditions between those that are the result of surgery and those that are the result of radiotherapy and other treatment methods using external energy sources. This review aims to clarify out current understanding of these three clinical problems and draws attention to the role of reconstructive surgery, particularly when dealing with bladder neck contractures, prostatic urethral stenoses and urorectal fistula. This also shows that the nature of the problem, the recovery time after treatment and the degree of functional recovery is radically different in the surgical as against the non-surgical group, to a degree that the authors believe is not sufficiently stressed when patients are counselled and consented before their primary treatment. To review the less common and not widely discussed, but much more serious complications of prostate cancer treatment of: urethral stricture, bladder neck contracture and urorectal fistula., The treatment options for patients with organ-confirmed prostate cancer include: radical prostatectomy (RP), brachytherapy (BT), external beam radiotherapy (EBRT), high-intensity focussed ultrasound (HIFU) and cryotherapy; with each method or combination of methods having associated complications., Complications resulting from RP are relatively easy to manage, with rapid recovery and return to normal activities, and usually a return to normal bodily functions., However, after non-surgical treatments, i.e. BT, EBRT, HIFU and cryotherapy, these same problems are more difficult to treat with a much slower return to a much lower level of function., When counselling patients about the primary treatment of prostate cancer they should be advised that although the same type of complication may occur after surgical or non-surgical treatment, the scope and scale of that complication, the ease with which it is treated and the degree of restoration of normality after treatment, is altogether in favour of surgery in those for whom surgery is appropriate and who are fit for surgery. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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26. Immunhistochemical Expression of Galectin-3 in Cancer: A Review of the Literature.
- Author
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Çay, Tuğçe
- Subjects
GALECTINS ,GALACTOSIDASES ,LECTINS ,EMBRYOLOGY ,GROWTH ,CELL adhesion ,CELL proliferation ,CELL differentiation - Abstract
Copyright of Turkish Journal of Pathology is the property of Turkish Journal of Pathology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
- Published
- 2012
- Full Text
- View/download PDF
27. The sensitivity of fluorescent-light cystoscopy for the detection of carcinoma in situ (CIS) of the bladder: a meta-analysis with comments on gold standard.
- Author
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Isfoss, Björn L.
- Subjects
CANCER ,CYSTOSCOPY ,IN situ hybridization ,META-analysis ,URINARY organs - Abstract
What's known on the subject? and What does the study add? Fluorescent-light cystoscopy has a high sensitivity, relative to that of white light cystoscopy, for carcinoma in situ of the bladder. However, this systematic review reveals that the absolute sensitivity is unknown due to the absence of proper gold standard which is microscopic examination of whole bladders. [ABSTRACT FROM AUTHOR]
- Published
- 2011
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- View/download PDF
28. Mitochondrial Metabolism Inhibitors for Cancer Therapy.
- Author
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Ramsay, Emma, Hogg, Philip, and Dilda, Pierre
- Subjects
MITOCHONDRIA ,CANCER treatment ,METABOLISM ,CANCER cells ,PHOSPHORYLATION ,GLUCOKINASE ,ENZYME inhibitors ,GLYCOLYSIS ,ADENINE nucleotides - Abstract
Cancer cells catabolise nutrients in a different way than healthy cells. Healthy cells mainly rely on oxidative phosphorylation, while cancer cells employ aerobic glycolysis. Glucose is the main nutrient catabolised by healthy cells, while cancer cells often depend on catabolism of both glucose and glutamine. A key organelle involved in this altered metabolism is mitochondria. Mitochondria coordinate the catabolism of glucose and glutamine across the cancer cell. Targeting mitochondrial metabolism in cancer cells has potential for the treatment of this disease. Perhaps the most promising target is the hexokinase-voltage dependent anion channel-adenine nucleotide translocase complex that spans the outer- and inner-mitochondrial membranes. This complex links glycolysis, oxidative phosphorylation and mitochondrial-mediated apoptosis in cancer cells. This review discusses cancer cell mitochondrial metabolism and the small molecule inhibitors of this metabolism that are in pre-clinical or clinical development. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
29. Bone morphogenetic protein signalling activity distinguishes histological subsets of paediatric germ cell tumours.
- Author
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Fustino, N., Rakheja, D., Ateek, C. S., Neumann, J. C., and Amatruda, J. F.
- Published
- 2011
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30. Renal glomerular alterations in patients with cancer: a clinical and immunohistochemical autopsy study.
- Author
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Faria, Tamara Veiga, Baptista, Maria Alice Ferreira, Burdmann, Emmanuel A., and Cury, Patrícia M.
- Subjects
GLOMERULONEPHRITIS ,KIDNEY diseases ,AUTOPSY ,CANCER ,IMMUNOHISTOCHEMISTRY ,TUMOR markers - Abstract
Background: Membranous glomerulonephritis (MGN) can be found in patients with cancer as a paraneoplastic syndrome or it could be manifested clinically before tumor detection. The aim of this study was to evaluate the frequency and type of renal histopathological alterations in patients with malignancy that died without cancer treatment and were submitted to necropsy. Methods: Patient's demographical and clinical data collection and laboratory tests (serum creatinine and urine sample) were evaluated. Results: Kidney fragments from 21 patients were obtained and studied by light microscopy after habitual staining. Immunohistochemistry studies were performed with monoclonal immunoglobulin and tumor markers. Patients' mean age was 71 years and 62% were male. The most frequent tumor was gastric cancer (five cases), followed by colon and oral cavity (three cases each). In 67% of the cases, malignancy was the main cause of death. Serum creatinine was increased in 10 cases, proteinuria in 15, and hematuria was present in 8 cases. The most usual glomerular lesion found was thickening of basement membrane (BM) of the capillary loops. There were two cases of IgA nephropathy, three cases of focal segmental glomerulosclerosis, and one case of MGN. Only in the patient with MGN and metastatic melanoma specific tumor markers were identified in the kidney. Conclusions: We observed a wide range of glomerular pathological changes and abnormal urinary sediments in almost all patients, but we found tumor marker deposits only in the patient with MGN. [ABSTRACT FROM AUTHOR]
- Published
- 2010
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31. High-intensity focused ultrasound: where are we and where to from here?
- Published
- 2010
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32. Mitochondria and Energetic Depression in Cell Pathophysiology.
- Author
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Seppet, Enn, Gruno, Marju, Peetsalu, Ants, Gizatullina, Zemfira, Nguyen, Huu Phuc, Vielhaber, Stefan, Wussling, Manfred H. P., Trumbeckaite, Sonata, Arandarcikaite, Odeta, Jerzembeck, Doreen, Sonnabend, Maria, Jegorov, Katharina, Zierz, Stephan, Striggow, Frank, and Gellerich, Frank N.
- Subjects
MITOCHONDRIA ,CELL death ,NEURODEGENERATION ,PATHOLOGICAL physiology ,MITOCHONDRIAL pathology ,CELL proliferation ,CARCINOGENESIS ,HYPOXEMIA ,PHOSPHORYLATION - Abstract
Mitochondrial dysfunction is a hallmark of almost all diseases. Acquired or inherited mutations of the mitochondrial genome DNA may give rise to mitochondrial diseases. Another class of disorders, in which mitochondrial impairments are initiated by extramitochondrial factors, includes neurodegenerative diseases and syndromes resulting from typical pathological processes, such as hypoxia/ischemia, inflammation, intoxications, and carcinogenesis. Both classes of diseases lead to cellular energetic depression (CED), which is characterized by decreased cytosolic phosphorylation potential that suppresses the cell's ability to do work and control the intracellular Ca
2+ homeostasis and its redox state. If progressing, CED leads to cell death, whose type is linked to the functional status of the mitochondria. In the case of limited deterioration, when some amounts of ATP can still be generated due to oxidative phosphorylation (OXPHOS), mitochondria launch the apoptotic cell death program by release of cytochrome c. Following pronounced CED, cytoplasmic ATP levels fall below the thresholds required for processing the ATP-dependent apoptotic cascade and the cell dies from necrosis. Both types of death can be grouped together as a mitochondrial cell death (MCD). However, there exist multiple adaptive reactions aimed at protecting cells against CED. In this context, a metabolic shift characterized by suppression of OXPHOS combined with activation of aerobic glycolysis as the main pathway for ATP synthesis (Warburg effect) is of central importance. Whereas this type of adaptation is sufficiently effective to avoid CED and to control the cellular redox state, thereby ensuring the cell survival, it also favors the avoidance of apoptotic cell death. This scenario may underlie uncontrolled cellular proliferation and growth, eventually resulting in carcinogenesis. [ABSTRACT FROM AUTHOR]- Published
- 2009
- Full Text
- View/download PDF
33. Mitochondria as targets for chemotherapy.
- Author
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Gogvadze, Vladimir, Orrenius, Sten, and Zhivotovsky, Boris
- Abstract
Mitochondrial malfunctioning is implicated in the pathogenesis of a variety of disorders, including cancer and multiple neurodegenerative diseases, such as Parkinson’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis, and Huntington’s disease. Disturbance of mitochondrial vital functions, e.g., production of ATP, calcium buffering capacity, and generation of reactive oxygen species, can be potentially involved in disease pathogenesis. Neurological disorders caused by mitochondrial deterioration are often associated with cell loss within specific brain regions. In contrast, mitochondrial alterations in tumor cells and the “Warburg effect” might lead to cell survival and resistance of tumor cells to chemotherapy. This review is devoted to the role of mitochondria in neurodegeneration and tumor formation, and describes how targeting of mitochondria can be beneficial in the therapy of these diseases, which affect a large human population. [ABSTRACT FROM AUTHOR]
- Published
- 2009
- Full Text
- View/download PDF
34. Mitochondrial DNA Instability and Metabolic Shift in Human Cancers.
- Author
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Hsin-Chen Lee and Yau-Huei Wei
- Subjects
MITOCHONDRIAL DNA abnormalities ,CANCER ,GLUCOSE ,GLYCOLYSIS ,TUMORS ,SPECTRUM analysis ,GENETIC mutation ,ONCOGENES ,CYTOCHROME oxidase ,CARCINOGENESIS ,METASTASIS ,BIOCHEMISTRY - Abstract
A shift in glucose metabolism from oxidative phosphorylation to glycolysis is one of the biochemical hallmarks of tumor cells. Mitochondrial defects have been proposed to play an important role in the initiation and/or progression of various types of cancer. In the past decade, a wide spectrum of mutations and depletion of mtDNA have been identified in human cancers. Moreover, it has been demonstrated that activation of oncogenes or mutation of tumor suppressor genes, such as p53, can lead to the upregulation of glycolytic enzymes or inhibition of the biogenesis or assembly of respiratory enzyme complexes such as cytochrome c oxidase. These findings may explain, at least in part, the well documented phenomena of elevated glucose uptake and mitochondrial defects in cancers. In this article, we review the somatic mtDNA alterations with clinicopathological correlations in human cancers, and their potential roles in tumorigenesis, cancer progression, and metastasis. The signaling pathways involved in the shift from aerobic metabolism to glycolysis in human cancers are also discussed. [ABSTRACT FROM AUTHOR]
- Published
- 2009
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- View/download PDF
35. The ubiquitin system, disease, and drug discovery.
- Author
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Petroski, Matthew D.
- Subjects
UBIQUITIN ,DISEASES ,DRUG development ,PROTEASE inhibitors ,CANCER ,VIRUS diseases ,NEURODEGENERATION - Abstract
The ubiquitin system of protein modification has emerged as a crucial mechanism involved in the regulation of a wide array of cellular processes. As our knowledge of the pathways in this system has grown, so have the ties between the protein ubiquitin and human disease. The power of the ubiquitin system for therapeutic benefit blossomed with the approval of the proteasome inhibitor Velcade in 2003 by the FDA. Current drug discovery activities in the ubiquitin system seek to (i) expand the development of new proteasome inhibitors with distinct mechanisms of action and improved bioavailability, and (ii) validate new targets. This review summarizes our current understanding of the role of the ubiquitin system in various human diseases ranging from cancer, viral infection and neurodegenerative disorders to muscle wasting, diabetes and inflammation. I provide an introduction to the ubiquitin system, highlight some emerging relationships between the ubiquitin system and disease, and discuss current and future efforts to harness aspects of this potentially powerful system for improving human health. [ABSTRACT FROM AUTHOR]
- Published
- 2008
- Full Text
- View/download PDF
36. Molecular mechanisms underlying the MiT translocation subgroup of renal cell carcinomas.
- Author
-
Medendorp, K., van Groningen, J. J. M., Schepens, M., Vreede, L., Thijssen, J., Schoenmakers, E. F. P. M., van den Hurk, W. H., Geurts van Kessel, A., and Kuiper, R. P.
- Subjects
RENAL cell carcinoma ,KIDNEY tubules ,TUMORS ,CHROMOSOMES ,CANCER - Abstract
Renal cell carcinomas (RCCs) represent a heterogeneous group of neoplasms, which differ in histological, pathologic and clinical characteristics. The tumors originate from different locations within the nephron and are accompanied by different recurrent (cyto)genetic anomalies. Recently, a novel subgroup of RCCs has been defined, i.e., the MiT translocation subgroup of RCCs. These tumors originate from the proximal tubule of the nephron, exhibit pleomorphic histological features including clear cell morphologies and papillary structures, and are found predominantly in children and young adults. In addition, these tumors are characterized by the occurrence of recurrent chromosomal translocations, which result in disruption and fusion of either the TFE3 or TFEB genes, both members of the MiT family of basic helix-loop-helix/leucine-zipper transcription factor genes. Hence the name MiT translocation subgroup of RCCs. In this review several features of this RCC subgroup will be discussed, including the molecular mechanisms that may underlie their development. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]
- Published
- 2007
- Full Text
- View/download PDF
37. HIF-1 mediates the Warburg effect in clear cell renal carcinoma.
- Subjects
PHYSIOLOGY ,PROTEINS ,CANCER ,GLUCOSE - Abstract
Abstract  Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that functions as a master regulator of oxygen homeostasis in all metazoan species. O2-dependent hydroxylation of two proline residues in the HIF-1α subunit is necessary for the binding of the von HippelâLindau (VHL) protein, which is a component of a ubiquitin protein ligase that ubiquitinates HIF-1α, leading to its degradation by the proteasome. In the majority of cases of the clear cell type of renal carcinoma, both VHL genes are inactivated by mutation or epigenetic silencing, leading to dysregulated HIF-1 transcriptional activity. VHL loss-of-function leads, under aerobic conditions, to a HIF-1-dependent reprogramming of glucose and energy metabolism that includes increased glucose uptake, glycolysis, and lactate production accompanied by a reciprocal decrease in respiration. These findings delineate for the first time the molecular mechanisms underlying the Warburg effect in a human cancer. [ABSTRACT FROM AUTHOR]
- Published
- 2007
- Full Text
- View/download PDF
38. The Stem Cell Identity of Testicular Cancer.
- Author
-
Clark, Amander T.
- Subjects
TESTICULAR cancer ,EMBRYONIC stem cells ,GERM cells ,TUMORS ,STEM cells - Abstract
Testicular germ cell tumors account for 1% of all cancers, and are the most common malignancies to affect males between the ages of 15 and 34. Understanding the pathogenesis of testis cancer has been challenging because the molecular and cellular events that result in the formation of germ cell tumors are hypothesized to occur during human fetal development. In this review, the molecular pathways involved in human testis cancer will be presented based on our research in human embryonic stem cells (hESCs), and also research using animal models. Testis germ cell tumors are unique in that the normal germ cell from which the tumor is derived has distinct stem cell characteristics that are shared with pluripotent hESCs. In particular, normal fetal germ cells express the core pluripotent transcription factors NANOG, SOX2 and OCT4. In contrast to hESCs:, the germ line is not pluripotent. As a result, germ cell tumorigenesis may arise from loss of germ line-specific inhibitors which in normal germ cells prevent overt pluripotency and self-renewal and when absent in abnormal germ cells, result in the conversion to germ line cancer stem cells. At the conclusion of this review, a model for the molecular events involved in germ cell tumor forrnation and the relationship between germ cell tumorigenesis and stem cell biology will be presented. [ABSTRACT FROM AUTHOR]
- Published
- 2007
- Full Text
- View/download PDF
39. The clinical applications of high intensity focused ultrasound in the prostate.
- Author
-
Illing, Rowland and Chapman, Alexander
- Subjects
MEDICAL imaging systems ,PROSTATE cancer treatment ,CANCER treatment ,MEDICAL equipment ,DIAGNOSTIC imaging - Abstract
Purpose: To review the current status of high intensity focused ultrasound (HIFU) therapy in the prostate, in particular the treatment of prostate cancer. Materials and methods: Two trans-rectal devices are currently in clinical use; the SonablateR500 and AblathermR. These devices are compared and similarities and differences highlighted. Results: Outcomes from the primary treatment of prostate cancer, and HIFU as a salvage therapy are discussed. The rate of adverse events are described after each of these, and the role and safety of other therapies after primary HIFU failure are outlined. Factors which may influence outcome such as use of neo-adjuvant androgen suppression are discussed. Conclusions: Trans-rectal HIFU for prostate cancer is a promising technique with medium-term oncological results broadly comparable to standard therapies. It is the only form of therapy which is non-invasive and does not utilise ionising radiation. This is an exiciting field undergoing rapid developments, both in the technology and the way in which prostate cancer as a disease is managed. [ABSTRACT FROM AUTHOR]
- Published
- 2007
- Full Text
- View/download PDF
40. High intensity focused ultrasound: Physical principles and devices.
- Author
-
ter Haar, >Gail and Coussios, Constantin
- Subjects
MEDICAL imaging systems ,MEDICAL equipment ,DIAGNOSTIC ultrasonic imaging ,TUMORS ,ENDOCRINE glands - Abstract
High intensity focused ultrasound (HIFU) is gaining rapid clinical acceptance as a treatment modality enabling non-invasive tissue heating and ablation for numerous applications. HIFU treatments are usually carried out in a single session, often as a day case procedure, with the patient either fully conscious, lightly sedated or under light general anaesthesia. A major advantage of HIFU over other thermal ablation techniques is that there is no necessity for the transcutaneous insertion of probes into the target tissue. The high powered focused beams employed are generated from sources placed either outside the body (for treatment of tumours of the liver, kidney, breast, uterus, pancreas and bone) or in the rectum (for treatment of the prostate), and are designed to enable rapid heating of a target tissue volume, while leaving tissue in the ultrasound propagation path relatively unaffected. Given the wide-ranging applicability of HIFU, numerous extra-corporeal, transrectal and interstitial devices have been designed to optimise application-specific treatment delivery. Their principle of operation is described here, alongside an overview of the physical mechanisms governing HIFU propagation and HIFU-induced heating. Present methods of characterising HIFU fields and of quantifying HIFU exposure and its associated effects are also addressed. [ABSTRACT FROM AUTHOR]
- Published
- 2007
- Full Text
- View/download PDF
41. PRCC-TFE3 Renal cell carcinoma in a boy with a history of contralateral mesoblastic nephroma.
- Author
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Onder, Ali, Teomete, Uygar, Argani, Pedram, Toledano, Stuart, Zilleruelo, Gaston, and Rodriguez, Maria
- Subjects
RENAL cell carcinoma ,CANCER ,RENAL cancer ,X chromosome ,SEX chromosomes ,NEPHROBLASTOMA - Abstract
The genetics of renal tumors in children is widely recognized. However, most of the studies published to date emphasize the association between Wilms tumor and the WT-1 gene. Recently, a unique translocation between the X chromosome and chromosome 1 or t(X;1) has been described in several reports of renal cell carcinomas (RCCs) diagnosed in children and adolescents that results in PRCC-TFE3 gene fusion. We report here a 9-year old African-American boy with a history of a right congenital mesoblastic nephroma treated with nephrectomy and followed by annual checkups. After 9 years, he was diagnosed with a mass at the hilum of the left kidney during the work-up of new-onset hypertension. A limited biopsy revealed densely hyalinized connective tissue that was initially interpreted to be a hyalinized contralateral mesoblastic nephroma. The child received chemotherapy, but the mass continued to grow. He underwent a left nephrectomy, and the pathology was diagnostic for a clear cell RCC. Chromosomal analysis disclosed a t(X;1)(p11.2;q21) translocation, which is known to result in a PRCC-TFE3 gene fusion. The tumor showed nuclear labeling for TFE3 protein by immunohistochemistry, supporting the above diagnosis. He has been on hemodialysis, is tumor free, and has not been receiving chemotherapy for 24 months. This is the first report of a RCC as a second malignant neoplasm in a child treated for a congenital mesoblastic nephroma. [ABSTRACT FROM AUTHOR]
- Published
- 2006
- Full Text
- View/download PDF
42. The cellular functions of clathrin.
- Author
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Royle, S. J.
- Subjects
ENDOCYTOSIS ,MITOSIS ,BIOLOGICAL membranes ,ABSORPTION (Physiology) ,CELL cycle - Abstract
Membranes and proteins are moved around the cell in small vesicles. A protein coat aids the budding of such vesicles from donor membranes. The major type of coat used by the cell is composed of clathrin, a three-legged protein that can form lattice-like coats on membranes destined for trafficking. In this review, I outline what we know about clathrin and discuss some recent advances in understanding the basic biology of this fascinating molecule, which include building a molecular model of a clathrin lattice and discovery of a new function for clathrin that occurs during mitosis. [ABSTRACT FROM AUTHOR]
- Published
- 2006
- Full Text
- View/download PDF
43. Organisation des soins de proximité dans un réseau de cancérologie. Le projet lorrain ONCOLOR.
- Author
-
Carayon, I., Krakowski, I., Klein, I., and Sommelet, D.
- Subjects
CANCER research ,MEDICAL research ,MEDICAL personnel ,MEDICAL care - Abstract
Copyright of Oncologie (Tech Science Press) is the property of Tech Science Press and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
- Published
- 2006
- Full Text
- View/download PDF
44. Thermal ablation and high-temperature thermal therapy: Overview of technology and clinical implementation.
- Author
-
Diederich, Chris J.
- Subjects
CANCER thermotherapy ,PHYSIOLOGICAL effects of temperature ,CANCER treatment ,TUMORS ,THERMAL conductivity ,FEVER ,DISEASES - Abstract
High-temperature hyperthermia or thermal therapy is being applied for destruction of cancerous tissue, eradication or reduction of benign tumours and targeted tissue modification and remodelling. Many of these high-temperature technologies provide a minimally-invasive alternative with lower morbidities compared to the traditional surgical procedures. The effects of high-temperature thermal exposure on tissues, examples of heating technology and procedures of clinical practice related to high-temperature thermal therapy are reviewed. This brief review encompasses interstitial, endocavity, intraluminal and external applications of RF, microwave, ultrasound, laser and thermal conduction energy sources. The technology is prevalent and in various levels of advancement, with the move toward more spatially-accurate and controllable heating systems combined with image-guidance and treatment verification warranted, especially for the treatment of cancer. [ABSTRACT FROM AUTHOR]
- Published
- 2005
- Full Text
- View/download PDF
45. Genetic basis of human testicular germ cell cancer: insights from the fruitfly and mouse.
- Author
-
Browne, Catherine M., Hime, Gary R., Koopman, Peter, and Loveland, Kate L.
- Subjects
GERM cells ,CANCER ,ETIOLOGY of diseases ,GENETICS ,GENETIC mutation ,FLIES ,MICE - Abstract
The prevalence of tumours of the germ line is increasing in the male population. This complex disease has a complex aetiology. We examine the contribution of genetic mutations to the development of germ line tumours in this review. In particular, we concentrate on fly and mouse experimental systems in order to demonstrate that mutations in some conserved genes cause pathologies typical of certain human germ cell tumours, whereas other mutations elicit phenotypes that are unique to the experimental model. Despite these experimental systems being imperfect, we show that they are useful models of human testicular germ cell tumourigenesis. [ABSTRACT FROM AUTHOR]
- Published
- 2005
- Full Text
- View/download PDF
46. Synergistic inhibitory effect of high-intensity focused ultrasound combined with chemotherapy on Dunning adenocarcinoma.
- Author
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Paparel, Philippe, Curiel, Laura, Chesnais, Sabrina, Ecochard, Rene, Chapelon, Jean-Yves, and Gelet, Albert
- Subjects
DRUG synergism ,DRUG therapy ,ADENOCARCINOMA ,CANCER ,THERAPEUTICS ,PHARMACOLOGY - Abstract
To evaluate the therapeutic effect of high-intensity focused ultrasound (HIFU) combined with chemotherapy (paclitaxel+ estramustine) on AT2 Dunning adenocarcinoma, as no satisfactory treatment for localized prostate cancer is available for patients with a poor prognosis, e.g. stage T3, a high Gleason score, or a prostate-specific antigen level of>15 ng/mL.Forty-one Dunning AT2 tumour-bearing Copenhagen rats were divided into four groups, i.e. control, chemotherapy, HIFU, and chemotherapy+ HIFU (the last three treated for 1 week). The growth in tumour volume was recorded for 3 weeks, the point at which tumour volume was considered to have doubled (doubling time). The growth curves of each group were plotted and evaluated statistically.At 30 days of follow-up the distributions of tumour volume with treatment group were significantly different (P < 0.001); volumes were significantly greater in the control than in the chemotherapy-only or in the HIFU-only group (bothP = 0.006). The greatest difference was between the chemotherapy+ HIFU and the control group. The tumour doubling times were 13.2 days for HIFU-only, 31.2 days for chemotherapy+ HIFU and 7.7 days for the controls.These results suggest that this combined therapy could be useful for treating patients with high-risk prostate cancer. [ABSTRACT FROM AUTHOR]
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- 2005
- Full Text
- View/download PDF
47. 3D proton MR spectroscopic imaging of prostate cancer using a standard spine coil at 1.5 T in clinical routine: a feasibility study.
- Author
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Lichy, Matthias, Pintaske, Jörg, Kottke, Raimund, Machann, Jürgen, Anastasiadis, Aristotelis, Roell, Stefan, Hennenlotter, Jörg, Diergarten, Till, Schick, Fritz, Stenzl, Arnulf, Claussen, Claus, Schlemmer, Heinz-Peter, Lichy, Matthias P, Pintaske, Jörg, Machann, Jürgen, Hennenlotter, Jörg, and Claussen, Claus D
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MAGNETIC resonance imaging ,MAGNETIC resonance ,SPECTRUM analysis ,IMAGING of cancer ,MAGNETIC resonance imaging of cancer ,CANCER spectroscopic imaging ,NUCLEAR magnetic resonance spectroscopy ,PILOT projects ,PROSTATE tumors ,RETROSPECTIVE studies ,DIAGNOSIS - Abstract
The objective of this study was to demonstrate the feasibility of 3D proton MR spectroscopic imaging (MRSI) of the prostate using a standard spine instead of a dedicated endorectal coil at 1.5 T. Twenty-eight patients (25 with biopsy proven prostate cancers and three patients with a benign prostate hyperplasia) were examined. MRI and MRSI were conducted with commercial array surface coils at 1.5 T. Ratios of choline (Cho), creatine (Cr) and citrate (Ci) were calculated for tumour, central and peripheral zone retrospectively, based on axial T2 weighed MR images and histology reports. Prostate cancer was characterized by significantly elevated (Cho+Cr)/Ci ratio compared with non-tumourous prostate tissue. The quality of all proton MR spectra was considered to be good or acceptable in 17/28 patients (61%) and poor in 11/28 (39%) examinations. In 20/25 patients with proven malignancy (80%), MRSI was considered to be helpful for the detection of prostate cancer. In 4/25 patients with proven malignancy (16%) who underwent seed implantation, radiotherapy or hormone deprivation before MR examination spectroscopy was of poor and non-diagnostic quality. MRSI of the prostate is feasible within clinical routine using the spine array surface coil at 1.5 T. It can consequently be applied to patients even with contraindications for endorectal coils. However, spectral quality and signal-to-noise ratio is clearly inferior to 3D MRSI examinations with endorectal coils. [ABSTRACT FROM AUTHOR]
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- 2005
- Full Text
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48. A new role for the von Hippel-Lindau tumor suppressor protein: stimulation of mitochondrial oxidative phosphorylation complex biogenesis.
- Author
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Eric Hervouet, Jocelyne Demont, Petr Pecina, Alena Vojtskov, Josef Houstek, Hlne Simonnet, and Catherine Godinot
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CELLS ,CANCER ,CELLULAR pathology ,VIRAL genetics - Abstract
Although mitochondrial deficiency in cancer has been described by Warburg, many years ago, the mechanisms underlying this impairment remain essentially unknown. Many types of cancer cells are concerned and, in particular, clear cell renal carcinoma (CCRC). In this cancer, the tumor suppressor gene, VHL (von Hippel-Lindau factor) is invalidated. Previous studies have shown that the transfection of the VHL gene in VHL-deficient cells originating from CCRCs could suppress their ability to form tumors when they were injected into nude mice. However, various additional genetic alterations are observed in such cancer cells. In order to investigate whether VHL invalidation was related to the mitochondrial impairment, we have studied the effects of wild-type VHL transfection into VHL-deficient 786-0 or RCC10 cells on their oxidative phosphorylation (OXPHOS) subunit contents and functions. We show that the presence of wild-type VHL protein (pVHL) increased mitochondrial DNA and respiratory chain protein contents and permitted the cells to rely on their mitochondrial ATP production to grow in the absence of glucose. In parallel to mtDNA increase, the presence of pVHL up regulated the mitochondrial transcription factor A, as shown by western blot analysis. In conclusion, in CCRCs, pVHL deficiency is one of the factors responsible for down-regulation of the biogenesis of OXPHOS complexes. [ABSTRACT FROM AUTHOR]
- Published
- 2005
49. Simple models improve the discrimination of prostate cancers from the peripheral gland by T1-weighted dynamic MRI.
- Author
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Kiessling, Fabian, Lichy, Matthias, Grobholz, Rainer, Heilmann, Melanie, Farhan, Nabeel, Michel, Maurice, Trojan, Lutz, Ederle, Joerg, Abel, Ulrich, Kauczor, Hans-Ulrich, Semmler, Wolfhard, Delorme, Stefan, and Michel, Maurice Stephan
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PROSTATE cancer ,MAGNETIC resonance imaging ,TUMORS ,ONCOLOGY ,CANCER diagnosis ,ANTIGENS ,BIOLOGICAL models ,CANCER ,COMPARATIVE studies ,DIAGNOSTIC imaging ,DYES & dyeing ,DIGITAL image processing ,RESEARCH methodology ,MEDICAL cooperation ,MICROCIRCULATION ,PHARMACOKINETICS ,PROSTATE ,PROSTATE tumors ,PROSTATECTOMY ,RESEARCH ,EVALUATION research ,CONTRAST media ,RECEIVER operating characteristic curves ,DIAGNOSIS - Abstract
Evaluation of the accuracy of descriptive and physiological parameters calculated from signal intensity-time curves using T1-weighted dynamic contrast enhanced MRI (DCE MRI) to differentiate prostate cancers from the peripheral gland. Twenty-seven patients with prostate cancers were examined with DCE MRI prior radical prostatectomy. Regions of interest were defined in tumors and non-affected areas in the peripheral zone. Dynamic data were parameterized in amplitude and exchange rate constant (kep) using a two-compartment model. Additionally, relative slope during 26, 39, 52 and 65 s, areas under the curve (AUC) and time to start of signal intensity increase (tlag) were determined. Vessel density (VD) of excised prostates was quantified in tumor areas using a CD34 stain. The parameter slope52 showed 20% higher values (P<0.001) in tumors than in the peripheral gland and compared with the other parameters the largest area under the ROC curve (0.81). The minimum total error rate was attained at a cut-point of 0.021, yielding a sample value of sensitivity and specificity of 70% and 88%, respectively, and a bias-corrected sum of sensitivity and specificity of 1.54. In addition, amplitude (P<0.001), kep (P=0.03) and AUC (P<0.001) were significantly higher in tumors. tlag did not discriminate carcinomas from glandular tissue. VD was higher in tumors than in the non-affected peripheral prostate (P=0.05). However, none of the dynamic parameters in carcinomas showed a significant correlation with VD or Gleason score. Although pharmacokinetic modeling in DCE MRI showed potential to discriminate prostate cancers from peripheral prostate tissue, descriptive parameters of the early signal enhancement after contrast media injection reached higher sensitivity and specificity. [ABSTRACT FROM AUTHOR]
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- 2004
- Full Text
- View/download PDF
50. Cost-analysis of staging methods for lymph nodes in patients with prostate cancer: MRI with a lymph node-specific contrast agent compared to pelvic lymph node dissection or CT.
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Hövels, Anke M., Heesakkers, Roel A. M., Adang, Eddy M., Jager, Gerrit J., Barentsz, Jelle O., and Hövels, Anke M
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PROSTATE cancer ,LYMPH nodes ,LYMPHATICS ,CANCER - Abstract
The aim of this study was to compare the costs of three strategies in patients with prostate cancer in a specific setting: firstly, a strategy including MR lymphography (MRL) in which pelvic lymph node dissection (PLND) is foregone in case of a negative result. The second strategy involves computed tomography (CT) followed by a biopsy or PLND. The third strategy consists of PLND without imaging beforehand. A decision analytic model was constructed. This model represented the diagnostic process for patients with prostate cancer and intermediate or high risk for nodal metastases, comparing the costs of the three strategies. Cost analysis was done from the health care perspective. The model indicated that the expected costs for the MRL strategy were 2,527 euro. The expected costs for the strategy using CT were 3,837 euro and for PLND 3,994 euro. These results show that potential savings performing MRL instead of CT were 1,310 euro and 1,467 euro for PLND. Sensitivity analyses show that variation in costs of PLND was most influential on the costs of all strategies. However, the overall savings pattern did not alter. Average costs of MRL staging in our institution are less than for CT and PLND in staging lymph nodes of patients with prostate cancer and who are intermediate or high risk for nodal metastases. [ABSTRACT FROM AUTHOR]
- Published
- 2004
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