scholarly journals EMBR-29. PEDIATRIC MEDULLOBLASTOMA PATIENT WITH MULTIPLE MIDLINE DEFECTS, A CASE REPORT

2021 ◽  
Vol 23 (Supplement_1) ◽  
pp. i12-i12
Author(s):  
Sydney Peck ◽  
Emily Owens ◽  
Amy Smith
Keyword(s):  
Tumor Cells ◽  
Cleft Lip ◽  
Treatment Strategies ◽  
Mycn Amplification ◽  
Group 4 ◽  
Pediatric Medulloblastoma ◽  
Midline Defects ◽  
The Family ◽  
Group 3 ◽  
Therapy Strategies

Abstract Medulloblastoma (MB) is the most common malignant central nervous system (CNS) cancer diagnosed in childhood and is divided into four subtypes: WNT-activated, SHH-activated, Group 3 (Non-WNT, Non-SHH), and Group 4 (Non-WNT, Non-SHH). Non-WNT/Non-SHH make up roughly two-thirds of MB and have the least understood pathogenesis with substantial intratumoral heterogeneity. Therapeutic targets and treatment strategies for Group 3 and 4 patients therefore remain unclear. In this report we present a 16-year-old patient with standard risk Group 4 medulloblastoma and multiple midline defects. The patient’s medical history was remarkable for a cleft lip (which healed in utero), a notable heart murmur, an inguinal hernia repair at 3 months of age, and significant pectus excavatum. This patient was diagnosed at age 12 with a MB. Tumor cells were negative for GAB-1, p53 stain was positive for approximately 1–2% of tumor cells, no evidence on monosomy 6, MYC or MYCN amplification. The family history is significant for paternal biliary cancer. The patient was treated as per ACNS0331 and is approximately 36 months off-therapy. This case presents an interesting instance of a CNS tumor arising within the microenvironment of wide-spread dysregulated development. Single cases do not provide any substantiative evidence. However, they do give insight on factors which may drive oncogenesis and may provide an indication as to whether we should continue to pursue targeted therapy for Group 3/4 uniformly or move towards personalized therapy strategies in this group patients.

scholarly journals PATH-25. APPLICABILITY OF A NOMOGRAM INCLUDING CLINICAL AND MOLECULAR VARIABLES IN THE STRATIFICATION OF RISK GROUPS IN PEDIATRIC MEDULLOBLASTOMA

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi148-vi148
Author(s):  
Bruna Mançano ◽  
Rui Reis ◽  
Leticia Leal ◽  
Flavia de Paula ◽  
Carlos Almeida Jr ◽  
...  
Keyword(s):  
Survival Rates ◽  
Disease Free Survival ◽  
Risk Groups ◽  
Molecular Characteristics ◽  
Childhood And Adolescence ◽  
Tumor Subtypes ◽  
Group 4 ◽  
Pediatric Medulloblastoma ◽  
Group 3 ◽  
Multiple Variables

Abstract Medulloblastoma is the most common type of malignant brain tumor that occurs during childhood and adolescence. Currently, this pathology comprises at least four different molecular tumor subtypes (WNT, SHH, group 3 or C and group 4 or D) which have their own molecular characteristics, distinct clinical presentations and are associated with different survival rates. The purpose is to evaluate the applicability of a nomogram that includes clinical and molecular variables in pediatric medulloblastomas in the routine of the Hospital de Cancer de Barretos. The series l consists of 85 pediatric patients from 0 to 18 years old, diagnosed with medulloblastoma attended at the Hospital de Cancer de Barretos (HCB), from January 2000 to December 2017. The molecular subgroups will be performed using the Nanostring technique. This research intends to implement a nomogram that uses several variables known and involved in the treatment and prognosis of patients, this nomogram with multiple variables will show the clinical and molecular effect of each variable to predict disease-free survival and survival overall in 3 and 5 years. Thus, we will have the opportunity to analyze these characteristics in order to improve survival and reduce morbidity and consequently mortality during treatment for the different subgroups of medulloblastomas.

scholarly journals Preclinical Models of Craniospinal Irradiation for Medulloblastoma

Cancers ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 133 ◽  
Author(s):  
Jennifer L. Stripay ◽  
Thomas E. Merchant ◽  
Martine F. Roussel ◽  
Christopher L. Tinkle
Keyword(s):  
Small Animal ◽  
Craniospinal Irradiation ◽  
Tumor Control ◽  
Preclinical Models ◽  
Treatment Interventions ◽  
Leptomeningeal Seeding ◽  
Group 4 ◽  
Pediatric Medulloblastoma ◽  
Group 3

Medulloblastoma is an embryonal tumor that shows a predilection for distant metastatic spread and leptomeningeal seeding. For most patients, optimal management of medulloblastoma includes maximum safe resection followed by adjuvant craniospinal irradiation (CSI) and chemotherapy. Although CSI is crucial in treating medulloblastoma, the realization that medulloblastoma is a heterogeneous disease comprising four distinct molecular subgroups (wingless [WNT], sonic hedgehog [SHH], Group 3 [G3], and Group 4 [G4]) with distinct clinical characteristics and prognoses has refocused efforts to better define the optimal role of CSI within and across disease subgroups. The ability to deliver clinically relevant CSI to preclinical models of medulloblastoma offers the potential to study radiation dose and volume effects on tumor control and toxicity in these subgroups and to identify subgroup-specific combination adjuvant therapies. Recent efforts have employed commercial image-guided small animal irradiation systems as well as custom approaches to deliver accurate and reproducible fractionated CSI in various preclinical models of medulloblastoma. Here, we provide an overview of the current clinical indications for, and technical aspects of, irradiation of pediatric medulloblastoma. We then review the current literature on preclinical modeling of and treatment interventions for medulloblastoma and conclude with a summary of challenges in the field of preclinical modeling of CSI for the treatment of leptomeningeal seeding tumors.

scholarly journals Case-based review: pediatric medulloblastoma

2017 ◽  
Vol 4 (3) ◽  
pp. 138-150 ◽  
Author(s):  
Cassie N Kline ◽  
Roger J Packer ◽  
Eugene I Hwang ◽  
David R Raleigh ◽  
Steve Braunstein ◽  
...  
Keyword(s):  
Multimodal Approach ◽  
Ongoing Research ◽  
Group 4 ◽  
Pediatric Medulloblastoma ◽  
Life Threatening ◽  
The Central Nervous System ◽  
Group 3 ◽  
Multiagent Chemotherapy ◽  
Active Investigation

AbstractMedulloblastoma is the most common malignant brain tumor affecting children. These tumors are high grade with propensity to metastasize within the central nervous system and, less frequently, outside the neuraxis. Recent advancements in molecular subgrouping of medulloblastoma refine diagnosis and improve counseling in regards to overall prognosis. Both are predicated on the molecular drivers of each subgroup—WNT-activated, SHH-activated, group 3, and group 4. The traditional therapeutic mainstay for medulloblastoma includes a multimodal approach with surgery, radiation, and multiagent chemotherapy. As we discover more about the molecular basis of medulloblastoma, efforts to adjust treatment approaches based on molecular risk stratification are under active investigation. Certainly, the known neurological, developmental, endocrine, and psychosocial injury related to medulloblastoma and its associated therapies motivate ongoing research towards improving treatment for this life-threatening tumor while at the same time minimizing long-term side effects.

scholarly journals Comparative efficacy of melatonin in attenuation of endotoxin/LPS induced hepatotoxicity in BALB/c mice

2018 ◽  
Vol 7 (6) ◽  
pp. 1191
Author(s):  
Ammara Khan ◽  
Ayesha Afzal ◽  
Abdul Rauf ◽  
Akbar Waheed
Keyword(s):  
Therapeutic Potential ◽  
Histopathological Examination ◽  
Single Agent ◽  
Treatment Strategies ◽  
Organ Damage ◽  
Multiple Organ ◽  
E Coli ◽  
Group 4 ◽  
Group 3 ◽  
Set Up

Background: Sepsis is characterized by overwhelming surge of cytokines and oxidative stress to one of many factors, gram negative bacteria commonly implicated. Despite major expansion and elaboration of sepsis pathophysiology and therapeutic approach; death rate remains very high in septic patients due to multiple organ damage including hepatotoxicity. The present study was aimed to ascertain the adequacy of melatonin (10mg/kg i.p), and its comparability with dexamethasone (3mg/kg i.p), delivered separately and collectively in endotoxin induced hepatotoxicity.Methods: The number of animals in each group was six. Endotoxin/LPS induced hepatotoxicity was reproduced in mice by giving LPS of serotype E. coli intraperitoneally. Preventive role was questioned by giving the experimental agent half an hour prior to LPS injection whereas therapeutic potential of the experimental agent was searched out via post LPS delivering. The extent of liver damage was adjudged via serum alanine aminotransferases (ALT) and aspartate aminotransferase (AST) estimation along with histopathological examination of liver tissue.Results: Melatonin was prosperous in aversion (Group 3) and curation (Group 4) of LPS invoked hepatotoxicity as evident by lessening of augmented ALT (≤0.01) and AST (≤0.01) along with restoration of pathological changes on liver sections (p≤0.05). Dexamethasone given before (Group5) and after LPS (Group 6) significantly (p≤0.05) attenuated LPS generated liver injury. Combination therapy with dexamethasone in conjunction with melatonin (Group 7) after LPS administration tapered LPS evoked hepatic dysfunction statistically considerably, however the result was comparable to single agent therapy.Conclusions: Melatonin set up promising results in endotoxin induced hepatotoxicity and can be used therapeutic adjuncts to conventional treatment strategies in sepsis induced liver failure. Combination therapies however generated no synergistic results.

scholarly journals Analysis of Instagram® Posts Referring to Cleft Lip

2020 ◽  
Vol 17 (20) ◽  
pp. 7404
Author(s):  
Magdalena Sycinska-Dziarnowska ◽  
Piotr Stepien ◽  
Joanna Janiszewska-Olszowska ◽  
Katarzyna Grocholewicz ◽  
Maciej Jedlinski ◽  
...  
Keyword(s):  
Congenital Anomaly ◽  
Social Media ◽  
Cleft Lip ◽  
Medical Information ◽  
Cleft Lip And Palate ◽  
Group 4 ◽  
Group 3 ◽  
The Difference ◽  
Group 2 ◽  
Group 1

Background: Social media has become a source of medical information. Cleft lip and palate is a visible congenital anomaly. The aim of the study was to analyze Instagram® posts on the topic of cleft lip. Methods: Instagram® posts with “#cleftlip” from March 2014–March 2017 were accessed. Separate lists of expressions (hashtags, meaningful words, words with emojis or emojis alone) were prepared for primary posts and for replies. Thirty expressions statistically most frequent in primary versus secondary posts and 30 in secondary versus primary posts were identified (Group 1) as well as 30 English words or hashtags (Group 2), non-English words or hashtags (Group 3) and emojis (Group 4). The frequencies of expressions were compared (Z-test for the difference of two population proportions). Results: There were 34,129 posts, (5427 primary posts and 28,702 replies), containing 62,163 expressions, (35,004 in primary posts). The occurrence of all expressions was 454,162, (225,418 in primary posts and 228,744 in replies). Posts with positive expressions such as “beautiful”, “love”, “cute”, “great”, “awesome” occurred more often than these with negative ones. In replies all emojis were positive. Conclusions: Numerous Instagram® posts referring to cleft lip are published and do provoke discussion. People express their solidarity and sympathize with persons affected by cleft.

scholarly journals MBRS-61. MOLECULAR SUB-GROUPING OF PEDIATRIC MEDULLOBLASTOMA: CORRELATION WITH CLINICAL AND HISTOLOGICAL FEATURES, A SINGLE INSTITUTIONAL STUDY

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii408-iii408
Author(s):  
Gauri Deshpande ◽  
Mamta Gurav ◽  
Omshree Shetty ◽  
Vinayak Kadam ◽  
Vishal Chaubey ◽  
...  
Keyword(s):  
P53 Protein ◽  
Age Groups ◽  
Large Cell ◽  
Protein Coding ◽  
Real Time Quantitative Pcr ◽  
Group 4 ◽  
Pediatric Medulloblastoma ◽  
Group 3 ◽  
Protein Immunoreactivity

Abstract INTRODUCTION Molecular subgroups of pediatric medulloblastomas are distinctive in infantile and non-infantile age-groups. METHODS Real-time quantitative PCR based GEP of customized 12 protein-coding genes was performed on 206 FFPE childhood medulloblastoma samples. FISH for MYC amplification, monosomy 6 and sequencing for CTNNB1 exon 3 mutation were done in relevant cases. H&E and reticulin-stained slides were used for histological subtyping. p53-protein immunoreactivity pattern was noted. RESULTS Infantile (n=33) comprised 57.6% SHH-activated (desmoplastic: 73.7%; MBEN: 15.8% and classic: 10.5%), 21.2% group 3 (large cell/anaplastic [LCA]: 28.6% and none were desmoplastic) and 12% group 4. 40% of group 3 patients died of disease and 21% of the SHH-activated (all desmoplastic) had subsequent local recurrence. Non-infantile (n=173) comprised 19.4% WNT-activated, 12.9% SHH-activated (15% classic, 30% desmoplastic, 10% paucinodular), 19.4% group 3 (63.3% classic & 26.7% LCA), 48.4% group 4 (73.3% classic, 5.3% desmoplastic, 10.7% paucinodular & 1.4% LCA), and non-WNT/non-SHH (NWNS), NOS (n=14,9%) and unclassified (n=4,2.6%). None of WNT-activated were desmoplastic/LCA histology. Non-infantile WNT-activated and group 3 MBs showed 90% monosomy 6 & CTNNB1 mutation, and 16.7% MYC-amplification respectively. 17.4% (13% spinal, 4.4% local) WNT-activated, 31% (12.5% local, 18.5% distant [spinal: 12.5%, intracranial:6%]) SHH-activated, 27% (18% both spinal and local, 9% spinal) group 3 and 31.5% (7.4% local, 5.5% intracranial, 11.2% spinal, 7.4% both spinal and local) group 4 showed metastases during follow up. CONCLUSIONS SHH-activated and group 3 are the common infantile subgroups but group 4 is not non-existent in infantile age. No desmoplastic (including paucinodular) histological subtype is of WNT- activated and group 3.

scholarly journals Magnetic resonance radiomics features and prognosticators in different molecular subtypes of pediatric Medulloblastoma

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0255500
Author(s):  
Feng-Chi Chang ◽  
Tai-Tong Wong ◽  
Kuo-Sheng Wu ◽  
Chia-Feng Lu ◽  
Ting-Wei Weng ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Prediction Models ◽  
Gray Level ◽  
Resonance Imaging ◽  
Molecular Subgroups ◽  
Characteristic Analysis ◽  
Group 4 ◽  
Pediatric Medulloblastoma ◽  
Group 3

Purpose Medulloblastoma (MB) is a highly malignant pediatric brain tumor. In the latest classification, medulloblastoma is divided into four distinct groups: wingless (WNT), sonic hedgehog (SHH), Group 3, and Group 4. We analyzed the magnetic resonance imaging radiomics features to find the imaging surrogates of the 4 molecular subgroups of MB. Material and methods Frozen tissue, imaging data, and clinical data of 38 patients with medulloblastoma were included from Taipei Medical University Hospital and Taipei Veterans General Hospital. Molecular clustering was performed based on the gene expression level of 22 subgroup-specific signature genes. A total 253 magnetic resonance imaging radiomic features were generated from each subject for comparison between different molecular subgroups. Results Our cohort consisted of 7 (18.4%) patients with WNT medulloblastoma, 12 (31.6%) with SHH tumor, 8 (21.1%) with Group 3 tumor, and 11 (28.9%) with Group 4 tumor. 8 radiomics gray-level co-occurrence matrix texture (GLCM) features were significantly different between 4 molecular subgroups of MB. In addition, for tumors with higher values in a gray-level run length matrix feature—Short Run Low Gray-Level Emphasis, patients have shorter survival times than patients with low values of this feature (p = 0.04). The receiver operating characteristic analysis revealed optimal performance of the preliminary prediction model based on GLCM features for predicting WNT, Group 3, and Group 4 MB (area under the curve = 0.82, 0.72, and 0.78, respectively). Conclusion The preliminary result revealed that 8 contrast-enhanced T1-weighted imaging texture features were significantly different between 4 molecular subgroups of MB. Together with the prediction models, the radiomics features may provide suggestions for stratifying patients with MB into different risk groups.

scholarly journals Evaluation and Comparison of Condylar Head Inclination With Respect to Glenoid Fossa in Cleft, Class III, and Class I Individuals

2020 ◽  
pp. 030157422096341
Author(s):  
Prutha Ganesh Khakhar ◽  
Pallavi Daigavane ◽  
Ranjit Kamble ◽  
Priyanka Niranjane ◽  
Hamza Dargahwala ◽  
...  
Keyword(s):  
Cleft Lip ◽  
Cleft Lip And Palate ◽  
P Value ◽  
Glenoid Fossa ◽  
Class Iii ◽  
Group 4 ◽  
Bilateral Cleft Lip ◽  
Condylar Head ◽  
Group 3 ◽  
Group 2

Background: Cleft lip and palate are the most common congenital craniofacial defects, which need early intervention with a multidisciplinary approach including surgeons, orthodontists, speech therapists, pedodontists, etc. Craniofacial growth is affected the most, leading to marked skeletal discrepancies. Constricted maxillary arch is one of the reasons for faulty occlusal inclined planes which results in abnormal loading of condyles, thus leading to temporomandibular disorders (TMDs) in cleft. Condylar head inclination helps to evaluate the position of condyle in the glenoid fossa. Thus, changing the position of condylar head in the glenoid fossa at an early age prevents further worsening of TMD condition. The purpose of this study was to evaluate condylar inclination in individuals with cleft lip and palate and compare it with non-cleft individuals. Method: The study comprised of 40 subjects aged between 9 and 12 years, divided into 4 groups (10 in each)—unilateral cleft lip and palate (UCLP), bilateral cleft lip and palate (BCLP), and class III and class I malocclusion. Scanned three-dimensional digital volume tomography (3D-DVT) images were taken, and condylar head inclination was evaluated and compared. Result: Significant findings were obtained when group 1 was compared to group 2, group 3, and group 4 ( P-value = .001). Also, when group 2 was compared to group 3 and group 4, the values were statistically significant with P-value = .001. Conclusion: Condylar head inclination was found to be most anteriorly angulated in the class III group compared to all the other groups. Unilateral cleft lip and palate had more anteriorly angulated condyle than bilateral cleft lip and palate.

Morphological Changes in the Rat Granulosa Cell Surface During Differentiation Induced by Estradiol and Gonadotropins

1977 ◽  
Vol 35 ◽  
pp. 484-485
Author(s):  
P. Bagavandoss ◽  
JoAnne S. Richards ◽  
A. Rees Midgley
Keyword(s):  
Cell Surface ◽  
Granulosa Cell ◽  
Morphological Changes ◽  
Follicular Development ◽  
Female Rats ◽  
Functional Changes ◽  
Group 4 ◽  
Group 3 ◽  
Group 5 ◽  
Group 2

During follicular development in the mammalian ovary, several functional changes occur in the granulosa cells in response to steroid hormones and gonadotropins (1,2). In particular, marked changes in the content of membrane-associated receptors for the gonadotropins have been observed (1).We report here scanning electron microscope observations of morphological changes that occur on the granulosa cell surface in response to the administration of estradiol, human follicle stimulating hormone (hFSH), and human chorionic gonadotropin (hCG).Immature female rats that were hypophysectcmized on day 24 of age were treated in the following manner. Group 1: control groups were injected once a day with 0.1 ml phosphate buffered saline (PBS) for 3 days; group 2: estradiol (1.5 mg/0.2 ml propylene glycol) once a day for 3 days; group 3: estradiol for 3 days followed by 2 days of hFSH (1 μg/0.1 ml) twice daily, group 4: same as in group 3; group 5: same as in group 3 with a final injection of hCG (5 IU/0.1 ml) on the fifth day.

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