scholarly journals Using Elevated Cholesterol Synthesis as a Prognostic Marker in Wilms’ Tumor: A Bioinformatic Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Yuanbin He ◽  
Xu Cui ◽  
Yu Lin ◽  
Yunjin Wang ◽  
Dianming Wu ◽  
...  
Keyword(s):  
Cholesterol Synthesis ◽  
Nuclear Division ◽  
Wilms Tumor ◽  
Dietary Cholesterol ◽  
Cytolytic Activity ◽  
Dc Function ◽  
Dismal Prognosis ◽  
Increased Risk ◽  
Elevated Cholesterol ◽  
Prognosis Model

Background. Wilms tumor is the most common renal malignancy of children. Identifying factors that could predict the prognosis of patients with Wilms tumor is clinically meaningful. Many studies found tumors with elevated cholesterol synthesis that are featured with dismal prognosis. Even in some clinical trials, people with excessive dietary cholesterol intake and high plasma low-density lipoprotein levels are observed to have increased risk for cancer. However, the role of cholesterol biosynthesis in Wilms tumor has not yet been well clarified. Methods. RNA sequencing transcriptome data and all corresponding clinicopathological information used in our study were downloaded from the TARGET database. High-throughput sequencing (Fragments Per Kilobase of transcript per Million fragments mapped) data sets of 130 tumor samples and 6 normal samples were obtained for further analysis. Results. Wilms tumor samples with higher activity of cholesterol synthesis are characterized with worse overall survival ( P < 0.05 ). In addition, Wilms tumor samples with mitigated activity of cholesterol synthesis are featured with better dendritic cell (DC) function and cytolytic activity ( P < 0.05 ). Furthermore, we constructed a prognosis model based on differential expressed cholesterol synthesis-related genes (DECSG), which could predict the OS of patients with Wilms tumor accurately. KEGG and GO analysis of differential expressed genes between tumor samples with high and low cholesterol synthesis indicated that DECSGs are highly enriched in “mitosis nuclear division,” “nuclear division,” “chromosome segregation,” “cell cycle,” “Spliceosome,” and “RNA transport.” Conclusions. In conclusion, our study reported increased cholesterol synthesis in Wilms tumor predicts a worse prognosis and mitigated cytolytic activity, DC function, and MHC I signature in the tumor microenvironment. We also constructed a prognosis model for predicting the OS of patients with good accuracy, which is promising in clinical translation. Future studies should focus on the detailed mechanism that caused increasing cholesterol which promotes tumor progression and undermines patients’ survival.

scholarly journals Ten Reasons Why People With Down Syndrome are Protected From the Development of Most Solid Tumors -A Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Marta Pilar Osuna-Marco ◽  
Mónica López-Barahona ◽  
Blanca López-Ibor ◽  
Águeda Mercedes Tejera
Keyword(s):  
Down Syndrome ◽  
Solid Tumors ◽  
Tumor Suppressor Genes ◽  
Wilms Tumor ◽  
Extra Chromosome ◽  
Germ Cell Tumors ◽  
Chromosome 21 ◽  
Testicular Tumors ◽  
Unique Pattern ◽  
Increased Risk

People with Down syndrome have unique characteristics as a result of the presence of an extra chromosome 21. Regarding cancer, they present a unique pattern of tumors, which has not been fully explained to date. Globally, people with Down syndrome have a similar lifetime risk of developing cancer compared to the general population. However, they have a very increased risk of developing certain tumors (e.g., acute leukemia, germ cell tumors, testicular tumors and retinoblastoma) and, on the contrary, there are some other tumors which appear only exceptionally in this syndrome (e.g., breast cancer, prostate cancer, medulloblastoma, neuroblastoma and Wilms tumor). Various hypotheses have been developed to explain this situation. The genetic imbalance secondary to the presence of an extra chromosome 21 has molecular consequences at several levels, not only in chromosome 21 but also throughout the genome. In this review, we discuss the different proposed mechanisms that protect individuals with trisomy 21 from developing solid tumors: genetic dosage effect, tumor suppressor genes overexpression, disturbed metabolism, impaired neurogenesis and angiogenesis, increased apoptosis, immune system dysregulation, epigenetic aberrations and the effect of different microRNAs, among others. More research into the molecular pathways involved in this unique pattern of malignancies is still needed.

scholarly journals Impact of Surveillance Imaging Modality on Survival After Recurrence in Patients With Favorable-Histology Wilms Tumor: A Report From the Children’s Oncology Group

2018 ◽  
Vol 36 (34) ◽  
pp. 3396-3403 ◽  
Author(s):  
Elizabeth A. Mullen ◽  
Yueh-Yun Chi ◽  
Emily Hibbitts ◽  
James R. Anderson ◽  
Katarina J. Steacy ◽  
...  
Keyword(s):  
Wilms Tumor ◽  
Imaging Modality ◽  
Substantial Reduction ◽  
Abdominal Ultrasound ◽  
Favorable Histology ◽  
Routine Surveillance ◽  
Surveillance Imaging ◽  
Increased Risk ◽  
Surveillance Programs ◽  
Chest X Ray

Purpose The use of computed tomography (CT) for routine surveillance to detect recurrence in patients with Wilms tumor (WT) has increased in recent years. The utility of CT, despite increased risk and cost, to improve outcome for these patients is unknown. We conducted a retrospective analysis with patients enrolled in the fifth National Wilms Tumor Study (NWTS-5) to determine if surveillance with CT correlates with improved overall survival (OS) after recurrence compared with chest x-ray (CXR) and abdominal ultrasound (US). Patients and Methods Overall, 281 patients with recurrent unilateral favorable-histology WT were reviewed to assess how WT recurrence was detected: sign/symptoms (SS), surveillance imaging (SI) with CT scan, or SI with CXR/US. Results The estimated 5-year OS rate after relapse was 67% (95% CI, 61% to 72%). Twenty-five percent of recurrences were detected with SS; 48.5%, with CXR/US; and 26.5%, with CT. Patients with SS had a 5-year OS rate of 59% (95% CI, 46% to 72%) compared with 70% (95% CI, 63% to 77%; P = .23) for those detected by SI. Recurrences detected by CT had a shorter median time from diagnosis to recurrence (0.60 years) compared with SS (0.91 years) or CXR/US (0.86 years; P = .003). For recurrences detected by SI, more tumor foci at relapse ( P < .001) and size of the largest focus greater than 2 cm ( P = .02) were associated with inferior OS. However, there was no difference in OS after relapse when recurrence was detected by CT versus CXR/US (5-year OS rate, 65% v 73%; P = .20). Conclusion In patients with favorable-histology WT, elimination of CT scans from surveillance programs is unlikely to compromise survival but would result in substantial reduction in radiation exposure and health care costs.

scholarly journals Effects of dietary cholesterol and fat on serum non-cholesterol sterols according to different apolipoprotein E subgroups among healthy men

2008 ◽  
Vol 100 (2) ◽  
pp. 373-379 ◽  
Author(s):  
Markku J. Nissinen ◽  
Helena Gylling ◽  
Tatu A. Miettinen
Keyword(s):  
Cholesterol Synthesis ◽  
Cholesterol Metabolism ◽  
Dietary Cholesterol ◽  
Serum Levels ◽  
High Cholesterol ◽  
High Fat ◽  
Low Fat ◽  
Apo E ◽  
The Impact ◽  
Low Cholesterol

The impact of apo E phenotypes on applicability of relative cholesterol synthesis (lathosterol:cholesterol) and absorption (ratios of cholestanol, campesterol and sitosterol to cholesterol) during diets of various cholesterol and fat content is unclear. We examined and compared with each other both relative and absolute synthesis and absorption among twenty-nine men, of whom eight, nine and twelve had apo E phenotypes 2 (2/2, 2/3, 2/4), 3 (3/3) and 4 (3/4, 4/4), respectively. Serum lipids, lipoproteins, sterols and cholesterol metabolism were examined on four subsequent diets: high-cholesterol high-fat (home diet; HD), low-cholesterol low-fat (LCLF), high-cholesterol low-fat (HCLF) and low-cholesterol high-fat (LCHF). LDL-cholesterol (LDL-C) level was about 40 % lower (P < 0·05) in apo E2 than apo E3 and E4 groups irrespective of dietary fat and cholesterol. Serum proportions of phytosterols were determined apo E-dependently on LCLF and HCLF, and those of lathosterol, cholestanol and campesterol were increased in apo E2 and E3 groups (P < 0·05 for each v. HD). Serum proportion of sitosterol reflected almost consistently apo E phenotype (r range+0·308 to+0·383; P range 0·214–0·011). Relative cholesterol synthesis and absorption reflected respective absolute values during each diet in the apo E4 group (r range+0·713 to+0·893; P < 0·05 for each), but only during HD (r+0·594; P = 0·015) in the apo E2+E3 group. The consumption of a high amount of fat did not interfere with cholesterol metabolism or serum levels of LDL-C differently in apo E phenotypes. Surrogate sterol markers of cholesterol metabolism reflected absolute ones (especially in the apo E4 group) and apo E phenotypes despite variable amounts of dietary cholesterol and fat.

Translocation Carcinomas of the Kidney After Chemotherapy in Childhood

2006 ◽  
Vol 24 (10) ◽  
pp. 1529-1534 ◽  
Author(s):  
Pedram Argani ◽  
Marick Laé ◽  
Edgar T. Ballard ◽  
Mahul Amin ◽  
Carlos Manivel ◽  
...  
Keyword(s):  
Lupus Erythematosus ◽  
Wilms Tumor ◽  
Conditioning Regimen ◽  
Young Patients ◽  
Molecular Data ◽  
Marrow Transplant ◽  
Cytotoxic Chemotherapy ◽  
Secondary Malignancy ◽  
Increased Risk ◽  
Hurler’S Syndrome

Purpose Children who survive cancer are at more than 19-fold increased risk of developing another malignancy. Renal cell carcinoma (RCC) occurring as a secondary malignancy is uncommon. Translocation RCC, bearing TFE3 or TFEB gene fusions, are recently recognized entities for which risk factors have not been identified. Patients and Methods We describe the clinical, pathologic, cytogenetic, and molecular data on six translocation RCCs that arose in five young patients who had received chemotherapy. Results The ages at time of diagnosis of the RCC ranged from 6 to 22 years. Histologically, these tumors showed typical features previously described for translocation RCCs. At the molecular level, three tumors contained the ASPL-TFE3 fusion, two contained Alpha-TFEB, and one contained PRCC-TFE3. The intervals between chemotherapy and the diagnosis of RCC ranged from 4 to 13 years. The indications for the antecedent chemotherapy were varied and included acute promyelocytic leukemia, acute myeloid leukemia with t(9;11), bilateral Wilms' tumor, systemic lupus erythematosus, and conditioning regimen of bone marrow transplant for Hurler's syndrome. Only the latter patient had also received radiation. Hence, among 39 genetically confirmed translocation RCCs in our personal experience, six (15%) have arisen in patients who had received cytotoxic chemotherapy. Conclusion Cytotoxic chemotherapy may predispose to the development of renal translocation carcinomas.

scholarly journals Impact of television on children and adolescents: A research review

2016 ◽  
pp. 917-929
Author(s):  
Ana Pesikan
Keyword(s):  
Children And Adolescents ◽  
Dietary Habits ◽  
Violent Behavior ◽  
Research Review ◽  
Negative Effects ◽  
Beneficial Effects ◽  
Positive Effects ◽  
Increased Risk ◽  
Elevated Cholesterol ◽  
The Impact

Media has one of the most important and under-recognized influence on health, development and behavior of children and adolescents. Television is still the most popular form of media among children and adolescents. In the last 50 years, more than a thousand researches have been carried out in the world showing the great impact of television on children and adolescents. Television shapes the attitudes, beliefs and behaviors of children and adolescents and strongly influences their perception of reality. The high impact of television is neither recognized by children nor adults; they estimate that the media affect all others except themselves. Television can positively influence a child?s prosocial behavior and acquisition of certain types of knowledge. However, the positive effects have been much less common and usually obtained at a younger age (3-5 years). Most of the studies provide a persistent and robust findings indicating the correlation between exposure to television and a variety of health problems (such as obesity, low physical activity, elevated cholesterol, diabetes, high blood pressure, etc.) and an increased risk of certain types of behavior (like poor dietary habits, less sleep, smoking, violent behavior, alcoholism, drug addiction, etc.). The research results show that the potentials of television with beneficial effects on children have not been realized; the list of negative effects is much longer and much more diverse; and strategies to reduce the negative effects of television do not apply. The documented findings on the impact of television should elicit serious concern, not just from parents and educators but from many others such as physicians, public health advocates, entertainment industry, politicians, and government.

scholarly journals SUN-172 A False Positive Result in Newborn Screening for Congenital Adrenal Hyperplasia (CAH) in a Girl with Beckwith Wiedemann Syndrome

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Barbara Leitao Braga ◽  
Klevia N Feitosa ◽  
Thamiris Freitas Maia ◽  
Guiomar Madureira ◽  
Mirian Yumie Nishi ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Newborn Screening ◽  
False Positive ◽  
Wilms Tumor ◽  
Total Testosterone ◽  
Adrenal Hyperplasia ◽  
Chromosome 11P15 ◽  
Positive Diagnosis ◽  
False Positive Diagnosis ◽  
Increased Risk

Abstract Background: Congenital Adrenal Hyperplasia (CAH) comprises a spectrum of autosomal recessive diseases, resulting in enzymatic defects in the cortisol secretion. CAH newborn screening can avoid neonatal mortality in children with the salt-wasting form and prevent incorrect gender assignments in females. The occurrence of false-positive results creates diagnostic difficulties presenting therapeutic implications. Beckwith Wiedemann Syndrome (BWS) is a congenital disease characterized by somatic overgrowth, increased risk of neonatal hypoglycemia, and development of embryonic tumors. BWS is due to (epi)genetic changes involving growth-regulating genes with good genotype-phenotype correlation. The adrenal gland is frequently involved and may present diffuse cytomegaly of the adrenal cortex1. We reported a BWS newborn girl with a false-positive diagnosis of CAH in the screening. Case report: The patient was born at 39 weeks from an uneventful cesarean section, 5.6kg (&gt;p97) and 52cm (&gt;p97), referred to the Endocrinology service due to abnormal neonatal tests (neonatal 17-OHP: 96ng/mL) collected at 6 days old. At 14 days old, she was 6.3 kg (Z:+5.59), and 58cm (Z:+2.47), BMI: 18.7 kg/m2 (Z:+4.45), and with typical female external genitalia, ruling out the diagnosis of classic CAH. She presented some syndromic characteristics as macroglossia, ogival palate, orbital hypertelorism, hepatomegaly, and umbilical hernia. At 1 month and 14 days old, serum 17OHP was 7.4ng/mL, androstenedione: 6.1 ng/mL, total testosterone: 279ng/dL, 11-deoxycortisol: 2.11ng/mL, cortisol: 5.0ug/dL, and ACTH: 54pg/mL. At five months old she evolved with normalization of serum 17OHP, androstenedione and testosterone levels (1.36ng/mL, &lt;0.50ng/mL, and 37ng/dL, respectively), but still with high DHEAS levels: 2913ng/mL. At 11 months old, DHEAS also normalized, confirming that it was transient hyperactivity of the zona reticulata. A molecular test was performed in a blood sample by MLPA, showing a gain of methylation in the imprinting control region 1 (ICR1) of chromosome 11p15, which controls two imprinted genes, H19 and IGF-2, confirming the clinical diagnosis of BWS. The hypermethylation of ICR1 is largely related to the Wilms tumor. The patient was diagnosed with bilateral Wilms tumor at 11 months old and undergone chemotherapy without adequate response requiring left nephrectomy at 1 year and 5 days old. Conclusion: We presented the first description of false-positive diagnosis of CAH in the newborn screening of a girl with Beckwith Wiedemann syndrome, probably due to a transient overactivation of the zona reticulata. References: 1.Brioude F, Kalish JM, Mussa A, Foster AC, Bliek J, Ferrero GB, et al. Expert consensus document: clinical and molecular diagnosis, screening and management of Beckwith-Wiedemann syndrome: an international consensus statement. Nat Rev Endocrinol. 2018;14(4):229-49.

Dietary Cholesterol Inhibits Whole-Body but Not Cerebrum Cholesterol Synthesis In Young Pigs

1994 ◽  
Vol 124 (5) ◽  
pp. 717-725 ◽  
Author(s):  
Shide Zhang ◽  
William W. Wong ◽  
David L. Hachey ◽  
Wilson G. Pond ◽  
Peter D. Klein
Keyword(s):  
Cholesterol Synthesis ◽  
Dietary Cholesterol ◽  
Whole Body ◽  
Young Pigs

Increased cholesterol synthesis via squalene monooxygenase to predict lethal prostate cancer.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 77-77 ◽  
Author(s):  
Konrad Hermann Stopsack ◽  
Travis Gerke ◽  
James Robert Cerhan ◽  
Lorelei A. Mucci ◽  
Jennifer R. Rider
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Cholesterol Synthesis ◽  
Watchful Waiting ◽  
Prostate Tissue ◽  
Health Study ◽  
Squalene Monooxygenase ◽  
Increased Risk ◽  
The Mean ◽  
Benign Prostate

77 Background: Prostate cancer cells rely on cholesterol for proliferation and androgen production. We recently demonstrated that increased expression of the second key enzyme of cholesterol synthesis, squalene monooxygenase (SQLE), is associated with higher prostate cancer-specific mortality (PCSM). We here validate findings in two additional prospective studies and investigate putative mechanisms. Methods: We analyzed the prospective prostatectomy cohorts within the Health Professionals Follow-up Study (HPFS) and the Physicians’ Health Study (PHS) as well as initially expectantly managed patients in the Swedish Watchful Waiting Study (SWWS). 258 lethal cancer cases and 469 patients who survived > 8 years without metastases were included. SQLE mRNA was measured in tumor specimens at diagnosis of all patients and in benign prostate tissue of 197 patients. Markers of tumor angiogenesis were assessed via immunohistochemistry in 169 HPFS patients. We estimated multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) using logistic regression. Results: Higher SQLE expression was confirmed to be predictive of higher PCSM in the validation prostatectomy cohort PHS. Combining the two prostatectomy cohorts, men with high SQLE expression ( > 1 standard deviation above the mean) were 6.7 times (95% CI, 2.9 to 15.8; p < 0.001) more likely to die from their cancer compared to men with the mean level of SQLE expression. A 10% higher ratio of SQLE mRNA expression in tumor vs. benign prostate tissue of the same patient was predictive of 42% higher PCSM (95% CI, 15% to 74%). Higher SQLE expression was strongly associated with increased angiogenesis markers (all p ≤ 0.001). This increased risk associated with high SQLE expression was not modified by statin use (p ≥ 0.52). In initially untreated patients in SWWS, a more modest association of tumor SQLE expression with PCSM was observed (p = 0.047). Conclusions: SQLE, the second rate-limiting enzyme of cholesterol synthesis, is associated with prostate cancer progression. Its expression at cancer diagnosis is predictive of lethal disease both after curative-intent prostatectomy and in a watchful waiting setting, possibly by facilitating micrometastatic disease.

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