Pure germinomas account for 40% of pineal tumors and are characterized by the lack of appreciable tumor markers, thus requiring a tumor biopsy for diagnosis. MicroRNAs (miRNA) have emerged as ...potential non-invasive biomarkers for germ cell tumors and may facilitate the non-invasive diagnosis of pure pineal germinomas.
A retrospective chart review was performed on all patients treated at the Children's Cancer Hospital Egypt diagnosed with a pineal region tumor between June 2013 and March 2021 for whom a research blood sample was available. Plasma samples were profiled for miRNA expression, and DESeq2 was used to compare between pure germinoma and other tumor types. Differentially expressed miRNAs were identified. The area under the curve of the receive;r operating characteristic curve was constructed to evaluate diagnostic performance.
Samples from 39 pediatric patients were available consisting of 12 pure germinomas and 27 pineal region tumors of other pathologies, including pineal origin tumors
= 17; pineoblastoma (
= 13) and pineal parenchymal tumors of intermediate differentiation (
= 4) and others
= 10; low-grade glioma (
= 6) and atypical teratoid rhabdoid tumor (
= 4). Using an adjusted
-value <0.05, three miRNAs showed differential expression (miR-143-3p, miR-320c, miR-320d; adjusted
= 0.0058,
= 0.0478, and
= 0.0366, respectively) and good discriminatory power between the two groups (AUC 90.7%,
< 0.001) with a sensitivity of 25% and a specificity of 100%.
Our results suggest that a three-plasma miRNA signature has the potential to non-invasively identify pineal body pure germinomas which may allow selected patients to avoid the potential surgical complications.
Abstract Introduction Optic pathway gliomas (OPG) are rare neoplasms in children with an unpredictable clinical course. There is significant controversy regarding the optimal management and outcome ...of these patients. Methods Charts of all patients with OPG diagnosed and treated at Children’s Cancer Hospital Egypt between August 2007 and December 2013 were retrospectively reviewed. Evaluation of the role of surgical, ophthalmological, endocrinological, neurological and treatment aspects of care were reviewed. Results 65 patients were included in this study, with a mean age of 5.3 years. OPG were chiasmatic (n=25), optic nerve (n=18), hypothalamic (n=7) and chiasmatic/ hypothalamic (n=7). Extensive involvement of the optic pathway was seen in an additional 8 patients. Twenty cases had NF1. Four cases underwent surgical debulking and 28 were biopsied (16 open, 11 stereotactic and one endoscopic). Nine of the 18 optic nerve tumors were managed by total excision. Twenty four patients did not undergo any surgical intervention. Forty five patients received chemotherapy. Histopathology revealed pilocytic (n=20), pilomyxoid (n=15), fibrillary astrocytoma (n=4), and grade I papillary-glioneuronal tumor (n=1). Non representative sample (n=1). The 4 years overall survival rate was 86.3% with mean follow-up period of 32.2 months. Conclusion The initial role of surgery in newly developed OPG is biopsy for tissue diagnosis and relief of the hydrocephalus if present, followed by chemotherapy. Chemotherapy decreases or stabilizes the tumor size in most of the cases, leading to preservation of both visual and endocrinal functions. The most significant prognostic factor confirmed in this study was the age of the patient.
Background
The survival of pineoblastoma patients is low, particularly in infants and those with metastatic disease. This study aimed to analyze the prognostic factors affecting the outcome of ...Pineoblastoma in different age groups.
Methods
A retrospective study included 33 patients. Twenty-two patients older than 3 years had upfront surgery, followed by induction CSI then 6 cycles of chemotherapy.
Eleven patients younger than 3 years underwent surgery, followed by induction chemotherapy then radiation therapy. Focal irradiation (54 Gy) was administrated in six patients, and CSI (23.4 Gy) with booster dose 30.6 Gy to the tumor bed in two patients followed by 4 cycles of chemotherapy.
Results
Patient’s age showed a significant impact on the outcome (
P
value = 0.001 for EFS and 0.002 for OS). The metastases’ presence did not impact the outcome negatively. The survival of patients with metastatic disease did not differ between age groups. However, age had a significant impact on the outcome of M0 disease, with 3-year EFS and OS of 65.3% and 74%, respectively, in the older group compared to 0% for both rates in younger patients. CSI showed a positive impact on survival. For all cases, the 3-year OS and EFS were 46.7% and 44.4%, respectively.
Conclusions
A multimodality approach is needed to treat this aggressive disease. Inadequate dose intensity affected our patients’ outcome negatively. A more aggressive approach using high-dose chemotherapy or CSI may be required to improve infantile pineoblastoma’s dismal outcome. Focal radiotherapy is not an efficacious treatment in infants due to its high-metastatic potential. Molecular typing should be considered to label patients who need a more intensified approach.
Aggresomes are transient microtubule-dependent inclusion bodies that sequester misfolded proteins and are ultimately removed by autophagy. Here we report the generation of a choroid plexus carcinoma ...cell line; Children's Cancer Hospital Egypt (CCHE)-45, which is characterized by the constitutive formation of aggresomes. When examining the autophagy pathway as the main route for aggresomes clearance, CCHE-45 cells displayed increased autophagy flux mediated by MAP1LC3B. MAP1LC3A-Variant1 gene expression was silenced by promoter methylation. Restoring MAP1LC3A-Variant1 expression resulted in the formation of MAP1LC3A positive autophagosmes and the disruption of the aggresomes' vimentin cage independent of MAP1LC3B positive autophagosomes. Our data supports the notion that basal quality control autophagy and vimentin cage clearance in CCHE-45 are mediated by MAP1LC3A. Hence we propose that absence of MAP1LC3A disrupts the autophagic pathway and leads to the failure of aggresome vimentin cage degradation. Consequently, this could represent a targetable pathway in autophagy-dependent cancers.
Background: Panicum turgidum, desert grass, has not reported any detailed phytochemical or biological study as yet Objective: To establish P. turgidum secondary metabolite profile and to assess its ...antihepatotoxic effect Materials and Methods: Ultra-performance liquid chromatography (UPLC) coupled to quadrupole high-resolution time of flight mass spectrometry (qTOF-MS) was used for large-scale secondary metabolites profiling in P. turgidum extract, alongside assessing median lethal dose (LD50) and hepatoprotective effect against carbon tetrachloride (CCl 4 ) intoxication Results: A total of 39 metabolites were identified with flavonoids as the major class present as O/C-glycosides of luteolin, apigenin, isorhamnetin and naringenin, most of which are first time to be reported in Panicum sp. Antihepatotoxic effect of P. turgidum crude extract was revealed via improving several biochemical marker levels and mitigation against oxidative stress in the serum and liver tissues, compared with CCl4 intoxicated group and further confirmed by histopathological examination. Conclusion: This study reveals that P. turgidum, enriched in C-flavonoids, presents a novel source of safe antihepatotoxic agents and further demonstrates the efficacy of UPLC-MS metabolomics in the field of natural products drug discovery.
Abbreviations used: UPLC: Ultra-performance liquid chromatography (UPLC), LD50: median lethal dose, MDA: malondialdehyde, GSH: glutathione reductase, CAT: catalase, SOD: superoxide dismutase, ALT: alanine aminotransferase, AST: aspartate aminotransferase, ALP: alkaline phosphatase, TG: triglycerides.
Alterations of BRAF are the most common known genetic aberrations in pediatric gliomas. They frequently are found in pilocytic astrocytomas, where genomic duplications involving BRAF and the poorly ...characterized gene KIAA1549 create fusion proteins with constitutive B-Raf kinase activity. BRAF V600E point mutations are less common and generally occur in nonpilocytic tumors. The development of BRAF inhibitors as drugs has created an urgent need for robust clinical assays to identify activating lesions in BRAF. KIAA1549-BRAF fusion transcripts have been detected in frozen tissue, however, methods for FFPE tissue have not been reported. We developed a panel of FFPE-compatible quantitative RT-PCR assays for the most common KIAA1549-BRAF fusion transcripts. Application of these assays to a collection of 51 low-grade pediatric gliomas showed 97% sensitivity and 91% specificity compared with fluorescence in situ hybridization or array comparative genomic hybridization. In parallel, we assayed samples for the presence of the BRAF V600E mutation by PCR pyrosequencing. The data further support previous observations that these two alterations of the BRAF, KIAA1549 fusions and V600E point mutations, are associated primarily with pilocytic astrocytomas and nonpilocytic gliomas, respectively. These results show that fusion transcripts and mutations can be detected reliably in standard FFPE specimens and may be useful for incorporation into future studies of pediatric gliomas in basic science or clinical trials.
Background: Primary vaginal malignancies are rare in children. Their management has evolved during the last decades from radical surgery to neoadjuvant chemotherapy followed by local control with ...conservative surgery or radiotherapy. Aim: To describe the presentation, management, and outcome of pediatric vaginal malignancies. Methods: Retrospective review of the medical records of children with 1ry vaginal malignancies who had been treated at the Children’s Cancer Hospital Egypt (CCHE)-57357 from June 2007 till December 2018. Results: During the 11 years, 34 pediatric patients with 1ry vaginal malignancies were identified. The histopathology was rhabdomyosarcoma (RMS) in 19 (55.9%) patients, germ cell tumor (GCT) in 13 (38.2%), and clear cell adenocarcinoma (CCA) in two (5.9%). Vaginal bleeding was the presenting symptom in 65% of the patients. The 5-year overall survival and event-free survival rates were 73.7% and 77.8%, respectively, in RMS patients. In GCT patients, the 5-year overall survival and event-free survival rates were 84.6% and 61.5%, respectively. One of the two CCA patients died because of disease progression and the other was alive with progressive disease. Conclusions: Primary vaginal tumors are rare in children and generally have a good prognosis. Treatment with chemotherapy only or with either conservative surgery or radiotherapy may achieve an excellent outcome in pediatric primary vaginal RMS and GCT.
Mycetoma is a chronic infectious disease of the subcutaneous tissue with a high morbidity. This disease is most commonly seen in countries between 30°N and 15°S of the equator, but cases have also ...been seen in Europe and the USA. Due to the lack of proper prevalence data, currently the true burden of this disease is not known. Mycetoma can be caused by a large variety of microorganisms, both bacteria and fungi. Treatment of the disease depends on the etiology of the causative agent. Actinomycetoma is usually treated with antibiotics only and has a decent cure rate; eumycetoma is treated with a combination of antibiotics and surgery. Unfortunately, for eumycetoma, recurrent infections are common and amputations are still needed in a large proportion of the patients.
Allelopathy is considered as a physiological phenomenon with ecological implications that have stimulatory or inhibitory effects on organisms. The aim of the present study was focused on the effect ...of Ulva lactuca aqueous extract on growth and some physiological and metabolic aspects as well as gene expression of both Dunaliella salina and Chlorella salina. Linoleic acid ethyl ester; Propanoic acid, 3-(methylthio); Ethanol, 2-(9-octadecenyloxy)-, (Z); Oleic Acid; and 9-Octadecynoic acid, methyl ester were active phytochemical compounds detected from the gas chromatography-mass spectrometry (GC–MS) analysis for the donor species aqueous extract. Data revealed that U. lactuca contains appreciable amounts of Mg, K, Ca, Na and Fe. Results showed a dramatic effect of U. lactuca extracts on growth of both D. salina and C. salina, which significantly increased at low extract concentrations and vice versa. The activity of total antioxidants achieved a gradual increase by increasing the extract concentration. Furthermore, the two recipient algae attained the highest value of protein polymorphism under 10% extract concentration. Sequences of soluble inorganic pyrophosphatases (sPPases) gene showed that, allelochemicals of U. lactuca extract reflected the highest genetic variation in C. salina and D. salina while causing a significant variation in different biochemical parameters.
PDF
