scholarly journals Clinical and molecular characteristics of WNT medulloblastomas

2019 ◽  
Vol 18 (4) ◽  
pp. 11-18
Author(s):  
L. I. Papusha ◽  
L. A. Yasko ◽  
A. P. Ektova ◽  
K. A. Voronin ◽  
A. A. Merishavyan ◽  
...  
Keyword(s):  
Gene Mutations ◽  
Favorable Outcome ◽  
Molecular Characteristics ◽  
Total Resection ◽  
Pediatric Hematology ◽  
National Medical ◽  
Molecular Group ◽  
International Data ◽  
Disease Free

WNTMBaccounts for about 10% of all medulloblastomas and have a favorable outcome in patients under 16 years according international data. We analyzed clinical and molecular characteristics of 20 patients with WNTMBpatients. The study was approved by the Independent Ethics Committee of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. The molecular group verification was performed by Nanostring gene expression profiling. The detection of CTNNB1 and TP53 gene mutations was carried out with Sanger sequencing. WNT Medulloblastoma are mainly classic (18/20 patients), non-metastatic (19/20 patients). Gross total resection was performed in 18 patients. Somatic CTNNB1 mutations were found in 17 patients, somatic TP53 were identified in 2 patients. 19/20 assessable patients are disease-free with a median follow-up of 23 months. One patient died from the progression of the disease. WNT MB patients have an overall favorable outcome, even for metastatic and TP53 positive tumors. The reduction in the intensity of therapy is indicated forWNTMB in case of reliable identification ofWNTMB.

scholarly journals Choroid plexus carcinoma in children

2021 ◽  
Vol 20 (1) ◽  
pp. 66-74
Author(s):  
A. F. Valiakhmetova ◽  
L. I. Papusha ◽  
A. V. Sanakoeva ◽  
L. V. Shishkina ◽  
O. I. Budanov ◽  
...  
Keyword(s):  
Choroid Plexus ◽  
Ethics Committee ◽  
Partial Resection ◽  
Event Free Survival ◽  
Total Resection ◽  
Free Survival ◽  
Pediatric Hematology ◽  
National Medical ◽  
Choroid Plexus Carcinomas ◽  
Optimal Treatment Strategy

Choroid plexus carcinomas (CPCs) are rare pediatric tumors with a generally poor prognosis. Currently there is no definite optimal treatment strategy for this neoplasm. This study is supported by the Independent Ethics Committee and approved by the Academic Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. This study included patients with a verified diagnosis of CPC at the age 0 to 18 years in the period from 01.01.2009 to 31.12.2019. A total of 32 patients were registered. The median age was 2.65 years; 93.5% of CPCs were localized in the lateral ventricles. Initial metastases were found in 21.8% of cases; 5-year event-free survival (EFS) in children with metastases was lower than in those who did not have metastases 29 ± 17% and 49 ± 12%. In our cohort, gross total resection (GTR) was performed in 65.6% of patients. The five-year EFS in patients with complete CPC removal was higher than in patients who underwent subtotal and partial resection (63 ± 13%, 12 ± 11%, and 0%, respectively). In addition, overall survival (OS) was slightly higher in those who underwent GTR compared with subtotal and partial resection (74 ± 12%, 67 ± 16%, and 0%, respectively). Of the 32 children with CPCs, 15 children received programm chemotherapy, 17 non-programm chemotherapy, 5-year EFS in patients who received programm and non-programm chemotherapy was 79 ± 11% and 0%, respectively (p = 0.0006), 5-year OS in patients who received programm and non-programm chemotherapy was 93 ± 7% and 36 ± 14% (p = 0.0054). 

scholarly journals Retinoblastoma genetics screening and clinical management

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Himika Gupta ◽  
Sivasankar Malaichamy ◽  
Ashwin Mallipatna ◽  
Sakthivel Murugan ◽  
Nallathambi Jeyabalan ◽  
...  
Keyword(s):  
Clinical Management ◽  
Detection Rate ◽  
Mutation Detection ◽  
Gene Mutations ◽  
Disease Recurrence ◽  
Germline Mutations ◽  
Global Studies ◽  
Mutation Detection Rate ◽  
Gene Deletions

Abstract Background India accounts for 20% of the global retinoblastoma (RB) burden. However, the existing data on RB1 gene germline mutations and its influence on clinical decisions is minimally explored. Methods Fifty children with RB underwent complete clinical examination and appropriate multidisciplinary management. Screening of germline RB1 gene mutations was performed through next-generation sequencing and Multiplex Ligation-dependent Probe Amplification (MLPA) analysis. The mutation and non-mutation groups were compared for clinical parameters especially severity, progression and recurrence. Results Twenty-nine patients had bilateral RB (BLRB) and 21 had unilateral RB (ULRB). The genetic analysis revealed 20 RB1 variations in 29 probands, inclusive of 3 novel mutations, known 16 mutations and heterozygous whole gene deletions. The mutation detection rate (MDR) was 86.2% in BLRB and 19% in ULRB. Associations of disease recurrence (p = 0.021), progression (p = 0.000) and higher percentage of optic nerve invasion, subretinal seeds and high-risk pathological factors were observed in the mutation group. Clinical management was influenced by the presence of germline mutations, particularly while deciding on enucleation, frequency of periodic follow up and radiotherapy. Conclusions We identified novel RB1 mutations, and our mutation detection rate was on par with the previous global studies. In our study, genetic results influenced clinical management and we suggest that it should be an essential and integral component of RB-care in India and elsewhere.

scholarly journals Neonatal screening and genotype-phenotype correlation of hyperphenylalaninemia in the Chinese population

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Xin Wang ◽  
Yanyun Wang ◽  
Dingyuan Ma ◽  
Zhilei Zhang ◽  
Yahong Li ◽  
...  
Keyword(s):  
Neonatal Screening ◽  
Phenylalanine Hydroxylase ◽  
Laboratory Data ◽  
Molecular Characteristics ◽  
Phenotype Correlation ◽  
Common Amino Acid ◽  
Appropriate Treatment ◽  
Clinical Presentations ◽  
Average Current

Abstract Background Hyperphenylalaninemia (HPA) is the most common amino acid metabolic disease involving phenylalanine hydroxylase (PAH, OMIM*612,349) deficiency or coenzyme tetrahydrobiopterin (BH4) deficiency. Patients with severe HPA often have a difficult life. Early diagnosis of HPA before the development of symptoms is possible via neonatal screening, facilitating appropriate treatment and reducing mortality and disability rates. This study revealed the prevalence, mutational and phenotypic spectrum, and prognosis of HPA by neonatal screening from January 2001 to September 2020 in Nanjing, Jiangsu Province, China. Methods Through a retrospective analysis of the information available in the neonatal screening database, the clinical presentations, laboratory data, molecular characteristics and treatment follow-up data of HPA patients detected by neonatal screening were evaluated. Results We diagnosed 181 patients with HPA from 1 to 957 newborns, giving an incidence of 1:6873. Among these patients, 177 were identified as PAH deficient and four patients were BH4 deficient. The average current age of the patients was 6.38 years old. The most common mutations of PAH were c.728 C > A/ p.Arg243Gln (13.83 %), c.158G > A/ p.Arg53His (9.57 %), c.611 A > G/ p.Tyr204Cys (7.44 %), and c.721 C > T/ p.Arg241Cys (6.38 %). Conclusions This study revealed the prevalence, phenotype-genotype, and prognosis of HPA in China and contributes to the updating of PAHD data for China and worldwide. Our study not only expanded the spectrum of phenotypes and genotype but also provided a valuable tool for improved genetic counseling and management of future cases.

scholarly journals Meningioma: A Review of Epidemiology, Pathology, Diagnosis, Treatment, and Future Directions

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 319
Author(s):  
Christian Ogasawara ◽  
Brandon D. Philbrick ◽  
D. Cory Adamson
Keyword(s):  
Central Nervous System ◽  
Current Treatment ◽  
Intracranial Tumor ◽  
Benign Tumors ◽  
Molecular Characteristics ◽  
Total Resection ◽  
Future Directions ◽  
Prediction Of Prognosis ◽  
Potential Use ◽  
Radiotherapy Treatment

Meningiomas are the most common intracranial tumor, making up more than a third of all primary central nervous system (CNS) tumors. They are mostly benign tumors that can be observed or preferentially treated with gross total resection that provides good outcomes. Meningiomas with complicated histology or in compromising locations has proved to be a challenge in treating and predicting prognostic outcomes. Advances in genomics and molecular characteristics of meningiomas have uncovered potential use for more accurate grading and prediction of prognosis and recurrence. With the study and detection of genomic aberrancies, specific biologic targets are now being trialed for possible management of meningiomas that are not responsive to standard surgery and radiotherapy treatment. This review summarizes current epidemiology, etiology, molecular characteristics, diagnosis, treatments, and current treatment trials.

scholarly journals THU0502 EFFICACY AND SAFETY OF SECUKINUMAB TREATMENT IN JUVENILE IDIOPATHIC ARTHRITIS PATIENTS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 489.3-489
Author(s):  
I. Kriulin ◽  
E. Alexeeva ◽  
T. Dvoryakovskaya ◽  
K. Isaeva ◽  
A. Chomakhidze ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Psoriatic Arthritis ◽  
Response To Therapy ◽  
Inactive Disease ◽  
Hla B27 ◽  
Serious Adverse Events ◽  
National Medical ◽  
Alternative Drug ◽  
Baseline Information

Background:Anti-IL-17A biologic drug secukinumab (SEC) proved to be effective for treatment of psoriatic arthritis. However data about its efficacy in juvenile idiopathic arthritis (JIA) are restricted to off-label experience.Objectives:To evaluate the effectiveness and safety of SEC in JIA patients in the National Medical Research Center of Children`s health, Moscow, Russia.Methods:25 patients started SEC therapy from 12/2017 to 11/2019 in single-center prospective study. 3 patients withdrew treatment: two patients (8%) due to AE (1 - allergy followed by MAS after first injection and 1 – leukopenia) and one patient (4%) – after 10 months of treatment due to secondary inefficacy. Among others, 14 patients which were successfully treated for 6 months or longer were included into analysis. At the baseline, information was collected on the characteristics of the onset of the disease, previous therapy and its success. Patients were monitored at least 1 time per year. At each visit, clinical and laboratory characteristics of JIA severity were assessed. Response to therapy was assessed using the ACRPedi 30/50/70/90 criteria, the C.Wallace criteria for inactive disease (WID) and clinical remission. AEs were assessed at each visit.Results:Among 14 patients received SEC for at least 6 months, 7 (50%) have enthesitis-related arthritis, one (7.1%) – persistent oligoarthritis, 4 (28.6%) – RF-negative polyarthritis, 2 (14.3%) – psoriatic arthritis. 6 patients (42.9%) were HLA-B27 positive. Median age of JIA onset was 8.8 (IQR 5:11), age at SEC initiation – 14 (9.9:16.1), disease duration before SEC start – 3.3 (2.7:5.8). 7 (50%) were biologics-naïve, 2 (14.3%) were previously treated with anti-TNF drug, 5 (35.7%) have 2 or more different biologics in anamnesis.SEC demonstrated high efficacy after the first injection resulting in JADAS-71 decreasing in all patients by median 4.3 (1.6:7.1) points and 7/7/5/2 patients (50%/50%/35.7%/14.3%) achieved ACR Pedi 30/50/70/90 response.After 6 months of treatment, WID was achieved by 7 (50%) patients, JADAS-71 decreased from baseline level 15.2 (12.7:20.5) to 0.8 (0:4.2) points, and 14/13/11/9 patients (100%/92.9%/78.6%/64.3%) achieved ACR Pedi 30/50/70/90 response. One patients who had active uveitis at SEC initiation remained with subactive uveitis; one patient with uveitis remission had not flare episodes during follow-up period. One patient (7.1%) had successfully treated evaluation of transaminases after 4-th injection.Conclusion:Secukinumab showed high effectiveness and safety in children with JIA and can be further used both as a first-line drug in JIA associated with HLA-B27, and as an alternative drug for the ineffectiveness of the standard treatment regimen with biologics. No serious adverse events were registered during follow-up period.Disclosure of Interests:Ivan Kriulin: None declared, Ekaterina Alexeeva Grant/research support from: Roche, Pfizer, Centocor, Novartis, Speakers bureau: Roche, Novartis, Pfizer., Tatyana Dvoryakovskaya: None declared, Ksenia Isaeva: None declared, Aleksandra Chomakhidze: None declared, Evgeniya Chistyakova: None declared, Olga Lomakina: None declared, Rina Denisova: None declared, Anna Mamutova: None declared, Anna Fetisova: None declared, Marina Gautier: None declared, Dariya Vankova: None declared, Elizaveta Krekhova: None declared, Meyri Shingarova: None declared, Alina Alshevskaya: None declared, Andrey Moskalev: None declared

scholarly journals TRIM25 regulates oxaliplatin resistance in colorectal cancer by promoting EZH2 stability

2021 ◽  
Vol 12 (5) ◽  
Author(s):  
Sha Zhou ◽  
Jianhong Peng ◽  
Liuniu Xiao ◽  
Caixia Zhou ◽  
Yujing Fang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Disease Free Survival ◽  
Free Survival ◽  
Epigenetic Regulator ◽  
Crc Management ◽  
Disease Free ◽  
Resistance To Chemotherapy

AbstractResistance to chemotherapy remains the major cause of treatment failure in patients with colorectal cancer (CRC). Here, we identified TRIM25 as an epigenetic regulator of oxaliplatin (OXA) resistance in CRC. The level of TRIM25 in OXA-resistant patients who experienced recurrence during the follow-up period was significantly higher than in those who had no recurrence. Patients with high expression of TRIM25 had a significantly higher recurrence rate and worse disease-free survival than those with low TRIM25 expression. Downregulation of TRIM25 dramatically inhibited, while overexpression of TRIM25 increased, CRC cell survival after OXA treatment. In addition, TRIM25 promoted the stem cell properties of CRC cells both in vitro and in vivo. Importantly, we demonstrated that TRIM25 inhibited the binding of E3 ubiquitin ligase TRAF6 to EZH2, thus stabilizing and upregulating EZH2, and promoting OXA resistance. Our study contributes to a better understanding of OXA resistance and indicates that inhibitors against TRIM25 might be an excellent strategy for CRC management in clinical practice.

Phase I Study of Fludarabine Plus Cyclophosphamide in Patients With Previously Untreated Low-Grade Lymphoma: Results and and Long-Term Follow-Up—A Report From the Eastern Cooperative Oncology Group

2000 ◽  
Vol 18 (5) ◽  
pp. 987-987 ◽  
Author(s):  
Howard S. Hochster ◽  
Martin M. Oken ◽  
Jane N. Winter ◽  
Leo I. Gordon ◽  
Bruce G. Raphael ◽  
...  
Keyword(s):  
Phase Ii ◽  
Bone Marrow Involvement ◽  
Survival Rates ◽  
Eastern Cooperative Oncology Group ◽  
Disease Free Survival ◽  
Low Grade ◽  
Survival Times ◽  
Free Survival ◽  
Disease Free

PURPOSE: To determine the toxicity and recommended phase II doses of the combination of fludarabine plus cyclophosphamide in chemotherapy-naive patients with low-grade lymphoma. PATIENTS AND METHODS: Previously untreated patients with low-grade lymphoma were entered onto dosing cohorts of four patients each. The cyclophosphamide dose, given on day 1, was increased from 600 to 1,000 mg/m2. Fludarabine 20 mg/m2 was administered on days 1 through 5. The first eight patients were treated every 21 days; later patients were treated every 28 days. Prophylactic antibiotics were required. RESULTS: Prolonged cytopenia and pulmonary toxicity each occurred in three of eight patients treated every 3 weeks. The 19 patients treated every 28 days, who were given granulocyte colony-stimulating factor as indicated, did not have undue nonhematologic toxicity. Dose-limiting toxicity was hematologic. At the recommended phase II/III dose (cyclophosphamide 1,000 mg/m2), grade 4 neutropenia was observed in 17% of all cycles and 31% of first cycles. Grade 3 or 4 thrombocytopenia was seen in only 1% of all cycles. The median number of cycles per patient was six (range, two to 11) for all patients enrolled. The response rate was 100% of 27 patients entered; 89% achieved a complete and 11% a partial response. Nineteen of 22 patients with bone marrow involvement had clearing of the marrow. Median duration of follow-up was more than 5 years; median overall and disease-free survival times have not been reached. Kaplan-Meier estimated 5-year overall survival and disease-free survival rates were 66% and 53%, respectively. CONCLUSION: The recommended dosing for this combination in patients with previously untreated low-grade lymphoma is cyclophosphamide 1,000 mg/m2 day 1 and fludarabine 20 mg/m2 days 1 through 5. The regimen has a high level of activity, with prolonged complete remissions providing 5-year overall and disease-free survival rates as high as those reported for other therapeutic approaches in untreated patients.

scholarly journals Treatment of adult acute lymphoblastic leukemia with intensive cyclical chemotherapy: a follow-up report

Blood ◽  
1991 ◽  
Vol 78 (11) ◽  
pp. 2814-2822 ◽  
Author(s):  
CA Linker ◽  
LJ Levitt ◽  
M O'Donnell ◽  
SJ Forman ◽  
CA Ries
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Disease Free Survival ◽  
Remission Induction ◽  
Cell Phenotype ◽  
Free Survival ◽  
Prognostic Features ◽  
Adult Acute Lymphoblastic Leukemia ◽  
Disease Free

Abstract We treated 109 patients with adult acute lymphoblastic leukemia (ALL) diagnosed by histochemical and immunologic techniques. Patients were excluded only for age greater than 50 years and Burkitt's leukemia. Treatment included a four-drug remission induction phase followed by alternating cycles of noncrossresistant chemotherapy and prolonged oral maintenance therapy. Eighty-eight percent of patients entered complete remission. With a median follow-up of 77 months (range, 48 to 111 months), 42% +/- 6% (SEM) of patients achieving remission are projected to remain disease-free at 5 years, and disease-free survival for all patients entered on study is 35% +/- 5%. Failure to achieve remission within the first 4 weeks of therapy and the presence of the Philadelphia chromosome are associated with a 100% risk of relapse. Remission patients with neither of these adverse features have a 48% +/- 6% probability of remaining in continuous remission for 5 years. Patients with T-cell phenotype have a favorable prognosis with 59% +/- 13% of patients achieving remission remaining disease-free compared with 31% +/- 7% of CALLA-positive patients. Intensive chemotherapy may produce prolonged disease-free survival in a sizable fraction of adults with ALL. Improved therapy is needed, especially for patients with adverse prognostic features.

Surgical Management of Petroclival Meningiomas: Defining Resection Goals Based on Risk of Neurological Morbidity and Tumor Recurrence Rates in 137 Patients

Neurosurgery ◽  
2005 ◽  
Vol 56 (3) ◽  
pp. 546-559 ◽  
Author(s):  
Kenneth M. Little ◽  
Allan H. Friedman ◽  
John H. Sampson ◽  
Masahiko Wanibuchi ◽  
Takanori Fukushima
Keyword(s):  
Cranial Nerve ◽  
Tumor Recurrence ◽  
Critical Role ◽  
Recurrence Rates ◽  
Total Resection ◽  
Petroclival Region ◽  
Petroclival Meningiomas ◽  
Increased Risk ◽  
Neurological Morbidity

Abstract OBJECTIVE: Meningiomas arising from the petroclival region remain a challenging surgical problem. Because of the substantial risk of neurological morbidity, uniformly pursuing a gross total resection (GTR) to minimize tumor recurrence rates may not be justified. We sought to define optimal resection goals based on risk factors for postoperative neurological morbidity and tumor recurrence rates. METHODS: This series represents our experience with 137 meningiomas arising from the petroclival region resected between June 1993 and October 2002. There were 38 male and 99 female patients with a mean age of 53 years. RESULTS: GTR was achieved in 40% of patients, and near total resection (NTR) was achieved in 40% of patients. One operative death occurred. Twenty-six percent of patients experienced new postoperative cranial nerve deficits, paresis, or ataxia when assessed at a mean follow-up of 8.3 months. The risk of cranial nerve deficits increased with prior resection (P < 0.001), preoperative cranial nerve deficit (P = 0.005), tumor adherence to neurovascular structures (P = 0.046), and fibrous tumor consistency (P = 0.005). The risk of paresis or ataxia increased with prior resection (P = 0.001) and tumor adherence (P = 0.045). Selective NTR rather than GTR in patients with adherent or fibrous tumors significantly reduced the rate of neurological deficits. Radiographic recurrence or progression occurred in 17.6% of patients at a mean follow-up of 29.8 months. Tumor recurrence rates after GTR and NTR did not differ significantly (P = 0.111). CONCLUSION: Intraoperatively defined tumor characteristics played a critical role in identifying the subset of patients with an increased risk of postoperative deficits. By selectively pursuing an NTR rather than a GTR, neurological morbidity was reduced significantly without significantly increasing the rate of tumor recurrence.

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