Molecular oncogenesis of craniopharyngioma: current and future strategies for the development of targeted therapies

2013 ◽  
Vol 119 (1) ◽  
pp. 106-112 ◽  
Author(s):  
Ibrahim Hussain ◽  
Jean Anderson Eloy ◽  
Peter W. Carmel ◽  
James K. Liu
Keyword(s):  
Tumor Recurrence ◽  
Genetic Basis ◽  
Tumor Resection ◽  
Genetically Engineered ◽  
Subtotal Resection ◽  
Intracranial Tumors ◽  
Optimal Response ◽  
Genomic Technologies ◽  
Molecular Studies ◽  
Generation Sequencing

Craniopharyngiomas are benign intracranial tumors that arise in the suprasellar and intrasellar region in children and adults. They are associated with calcification on neuroimaging, endocrinopathies, vision problems, and recurrence following subtotal resection. Molecular studies into their genetic basis have been limited, and therefore targeted medical therapies for this tumor have eluded physicians. With the discovery of aberrant Wnt/β-catenin pathway signaling in the pathogenesis of the most common subtype of craniopharyngioma (adamantinomatous), the identification of candidate genes and proteins implicated in this cascade provide attractive targets for future therapies. The recent development of a genetically engineered animal model of this tumor may also serve as a platform for evaluating potential therapies prior to clinical trials in humans. Advances in understanding the molecular pathogenesis of tumor recurrence have also been made, providing clues to develop adjuvant and neoadjuvant therapies to couple with tumor resection for optimal response rates. Finally, advances in genomic technologies and next-generation sequencing will underlie the translation of these genetic and molecular studies from the bench to clinical practice. In this review, the authors present an analysis of the molecular oncogenesis of craniopharyngioma and current directions in the development of novel therapies for these morbid, yet poorly understood brain tumors.

scholarly journals Intentional Subtotal Resection of Vestibular Schwannoma: A Reexamination

2019 ◽  
Vol 81 (02) ◽  
pp. 136-141 ◽  
Author(s):  
Ben A. Strickland ◽  
Kristine Ravina ◽  
Robert C. Rennert ◽  
Anna Jackanich ◽  
Ksenia Aaron ◽  
...  
Keyword(s):  
Facial Nerve ◽  
San Francisco ◽  
Tumor Recurrence ◽  
Tumor Resection ◽  
Gamma Knife Radiosurgery ◽  
Residual Tumor ◽  
Recurrence Risk ◽  
Tumor Control ◽  
Subtotal Resection ◽  
Nerve Recovery

Abstract Background Treatment of vestibular schwannomas (VS) remains controversial. Historical surgical series prioritized gross total resections (GTR); however, near total resections (NTR) and intentional subtotal resections (STR) aiming at improving cranial nerve outcomes are becoming more popular. Objective The main purpose of this article is to assess the tumor control and facial nerve outcomes in VS patients treated with STR or NTR. Methods VS patients undergoing STR or NTR at our institution between 1984 and 2016 were retrospectively reviewed. Patient demographics, extent of tumor resection, facial nerve injury, tumor recurrence, and need for Gamma Knife radiosurgery were analyzed. Facial nerve outcomes were quantified using House–Brackmann (HB) scores. Tumor regrowth was defined by the San Francisco criteria. Results Four-hundred fifty-seven VS resections were performed in a 32-year period. Sixty cases met inclusion criteria. The mean (range) follow-up duration was 30.9 (12–103) months. The STR cohort (n = 33) demonstrated regrowth in 12 patients (36.3%) at an average of 23.6 months. The NTR cohort (n = 27) did not experience tumor recurrence. Risk of tumor recurrence was positively correlated with preoperative tumor size (p = 0.002), size of residual tumor (p < 0.001), and STR (p < 0.001). Facial nerve outcomes of HB1–2 were observed in the majority of patients in both cohorts (74.1% NTR, 56% STR), though NTR was associated with a higher likelihood of facial nerve recovery (p = 0.003). Conclusion GTR remains the gold standard as long as facial nerve outcomes remain acceptable. NTR achieved superior tumor control and higher likelihood of facial nerve recovery compared with STR.

scholarly journals Next-generation microbiology: from comparative genomics to gene function

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Carolin M. Kobras ◽  
Andrew K. Fenton ◽  
Samuel K. Sheppard
Keyword(s):  
Data Science ◽  
Genetic Basis ◽  
Turning Point ◽  
Functional Genomic ◽  
Bacterial Cells ◽  
Next Generation ◽  
New Techniques ◽  
Molecular Microbiology ◽  
Genetic Complexity ◽  
Generation Sequencing

AbstractMicrobiology is at a turning point in its 120-year history. Widespread next-generation sequencing has revealed genetic complexity among bacteria that could hardly have been imagined by pioneers such as Pasteur, Escherich and Koch. This data cascade brings enormous potential to improve our understanding of individual bacterial cells and the genetic basis of phenotype variation. However, this revolution in data science cannot replace established microbiology practices, presenting the challenge of how to integrate these new techniques. Contrasting comparative and functional genomic approaches, we evoke molecular microbiology theory and established practice to present a conceptual framework and practical roadmap for next-generation microbiology.

scholarly journals Special Issue: Genetic Basis of Phenotypic Variation in Drosophila and Other Insects

Genes ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 1212
Author(s):  
J. Spencer Johnston ◽  
Carl E. Hjelmen
Keyword(s):  
Next Generation Sequencing ◽  
Genetic Basis ◽  
Genomic Sequence ◽  
Sequence Data ◽  
Complete Genomic Sequence ◽  
Special Issue ◽  
Model Species ◽  
Road Map ◽  
Generation Sequencing ◽  
Complete Genomic

Next-generation sequencing provides a nearly complete genomic sequence for model and non-model species alike; however, this wealth of sequence data includes no road map [...]

scholarly journals NI-01 Usefulness of preoperative evaluation of glioma elasticity by the magnetic resonance elastography

2020 ◽  
Vol 2 (Supplement_3) ◽  
pp. ii12-ii13
Author(s):  
Shinichiro Koizumi ◽  
Kazuhiko Kurozumi
Keyword(s):  
Elastic Modulus ◽  
Magnetic Resonance ◽  
Preoperative Evaluation ◽  
Tumor Resection ◽  
High Grade Glioma ◽  
Magnetic Resonance Elastography ◽  
Low Grade ◽  
Intracranial Tumors ◽  
Grade 3 ◽  
Malignant Grade

Abstract Introduction: The elasticity of intracranial tumors is difficult to assess non-invasively because the lesion is surrounded by the skull. Therefore, intracranial tumors have not been verified before surgery in terms of elastic modulus. Magnetic resonance elastography (MRE) is an epoch-making method capable of non-invasively imaging the elasticity of internal organs. We have examined the elasticity of meningiomas and pituitary adenomas and reported their usefulness. This time, we measured the glioma elasticity and verified usefulness of MRE. Method: Twenty-four gliomas (mean age 51.8±15.7 years, male: female = 17: 7) who underwent tumor resection after MRE imaging from July 2017 to May 2020 were targeted. The average elasticity was measured as an evaluation of tumor elastic modulus by MRE. Gliomas were divided into a low-grade glioma group (LGG: Grade 1, 2) and a high-grade glioma group (HGG: Grade 3, 4). Then, a comparative statistical study was conducted. Results: The average values of the average elasticity of LGG group (9 cases) and HGG group (15 cases) were 1.8±0.8 kPa and 2.5±0.8 kPa, respectively. The average elasticity was significantly higher in the HGG group (p=0.023). In the ROC analysis, the cutoff value was 2.1 kPa (sensitivity 70%, specificity 70%). Therefore, it was suggested that the tumor is likely to be HGG when the average elasticity is 2.1 kPa or more. Discussion: The glioma elasticity by preoperative MRE was significantly higher in the HGG group. Based on actual surgical experience, the tumor seems to be hard in the HGG group, and it was judged to be consistent with this our MRE research. The preoperative evaluation of glioma elasticity by MRE was considered useful, and it might help in planning a surgical strategy considering malignant grade.

scholarly journals Venous Thromboembolism Anticoagulation Prophylaxis Timing in Patients Undergoing Craniotomy for Tumor

2021 ◽  
Vol 2 (1) ◽  
Author(s):  
Hanna Algattas ◽  
Spencer E Talentino ◽  
Bradley Eichar ◽  
Abraham A Williams ◽  
Joseph M Murphy ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Clinical Judgment ◽  
Tumor Resection ◽  
The Elderly ◽  
Extent Of Resection ◽  
Subtotal Resection ◽  
Hemorrhagic Complication ◽  
Increased Risk ◽  
Hemorrhagic Complications ◽  
Prophylactic Anticoagulation

ABSTRACT BACKGROUND Prophylactic anticoagulation helps prevent postoperative venous thromboembolism (VTE) and time to initiation postcraniotomy has relied on clinical judgment and practice patterns. OBJECTIVE To compare risks of postoperative VTE and hemorrhage among patients undergoing tumor resection with initiation of prophylactic anticoagulation on postoperative day 1 (POD1) vs POD2. METHODS Adult patients undergoing craniotomy for tumor between 2008 and 2018 were retrospectively reviewed. Outcomes were recorded from the Electronic medical record (EMR) including deep vein thrombosis (DVT), pulmonary embolism (PE), and hemorrhage. RESULTS Of a total of 1168 patients undergoing craniotomy, 225 initiated anticoagulation on POD1 and 389 initiated on POD2. Of the 171 glioblastoma (GBM) cases, 64 initiated on POD1 and 107 on POD2. There were 9 DVTs (1.5%), 1 PE (0.20%), overall VTE rate of 1.6%, and 7 hemorrhagic complications (1.10%), 4 being clinically significant. The GBM cohort contained 4 DVTs (2.3%) and 3 hemorrhagic complications (1.80%). There was no increased risk of VTE or hemorrhage with anticoagulation initiated on POD2 compared to POD1 in either cohort. Multivariate analysis in both cohorts did not reveal a significant association between DVT, PE, or hemorrhagic complications with age, body mass index, GBM pathology, or extent of resection. Interestingly, glioma patients older than 70 with subtotal resection had a higher likelihood of suffering intracranial hemorrhage when anticoagulation was started on POD1 (odds ratio 12.98). CONCLUSION Risk of VTE or hemorrhagic complication did not significantly differ with prophylactic anticoagulation started on POD1 vs POD2. Early anticoagulation may certainly be considered in high risk cases; however, 1 group where risk may outweigh benefit is the elderly glioma population receiving a subtotal resection.

Cordotomy for patients with thoracic malignant astrocytoma

2010 ◽  
Vol 13 (4) ◽  
pp. 418-423 ◽  
Author(s):  
Masaya Nakamura ◽  
Osahiko Tsuji ◽  
Kanehiro Fujiyoshi ◽  
Kota Watanabe ◽  
Takashi Tsuji ◽  
...  
Keyword(s):  
Tumor Resection ◽  
Radical Resection ◽  
Subtotal Resection ◽  
Optimal Management ◽  
Malignant Astrocytoma ◽  
Initial Operation ◽  
Who Grade ◽  
Kaplan Meier ◽  
Malignant Astrocytomas ◽  
Grade Ii

Object The optimal management of malignant astrocytomas remains controversial, and the prognosis of these lesions has been dismal regardless of the administered treatment. In this study the authors investigated the surgical outcomes of cordotomy in patients with thoracic malignant astrocytomas to determine the effectiveness of this procedure. Methods Cordotomy was performed in 5 patients with glioblastoma multiforme (GBM) and 2 with anaplastic astrocytoma (AA). A Kaplan-Meier survival analysis was performed, and the associations of the resection level with survival and postoperative complications were retrospectively examined. Results Cordotomy was performed in a single stage in 2 patients with GBM and in 2 stages in 3 patients with GBM and 2 patients with AA. In the 2 patients with GBM, cordotomy was performed 2 and 3 weeks after a partial tumor resection. In the 2 patients with AA, the initial treatment consisted of partial tumor resection and subtotal resection combined with radiotherapy, and rostral tumor growth and progressive paralysis necessitated cordotomy 2 and 28 months later. One patient with a secondary GBM underwent cordotomy; the GBM developed 1 year after subtotal resection and radiotherapy for a WHO Grade II astrocytoma. Four patients died 4, 5, 24, and 42 months after the initial operation due to CSF dissemination, and 3 patients (2 with GBM and 1 with AA) remain alive (16, 39, and 71 months). No metastasis to any other organs was noted. Conclusions One-stage cordotomy should be indicated for patients with thoracic GBM or AA presenting with complete paraplegia preoperatively. In patients with thoracic GBM, even if paralysis is incomplete, cordotomy should be performed before the tumor disseminates through the CSF. Radical resection should be attempted in patients with AA and incomplete paralysis. If the tumor persists, radiotherapy and chemotherapy are indicated, and cordotomy should be reserved for lesions growing progressively after such second-line treatments.

scholarly journals Levels of Circulating PD-L1 Are Decreased in Patients with Resectable Cholangiocarcinoma

2021 ◽  
Vol 22 (12) ◽  
pp. 6569
Author(s):  
Christoph Roderburg ◽  
Sven H. Loosen ◽  
Jan Bednarsch ◽  
Patrick H. Alizai ◽  
Anjali A. Roeth ◽  
...  
Keyword(s):  
Tumor Recurrence ◽  
Tumor Biology ◽  
Tumor Resection ◽  
Postoperative Outcome ◽  
Serum Levels ◽  
Strong Trend ◽  
Programmed Cell Death 1 ◽  
Early Tumor ◽  
Circulating Levels

Tumor resection represents the only curative treatment option for patients with biliary tract cancers (BTCs), including intrahepatic cholangiocarcinoma (CCA), perihilar and extrahepatic CCA and gallbladder cancer. However, many patients develop early tumor recurrence and are unlikely to benefit from surgery. Therefore, markers to identify ideal surgical candidates are urgently needed. Circulating programmed cell death 1 ligand 1 (PD-L1) has recently been associated with different malignancies, including pancreatic cancer which closely resembles BTC in terms of patients’ prognosis and tumor biology. Here, we aim at evaluating a potential role of circulating PD-L1 as a novel biomarker for resectable BTC. Methods: Serum levels of PD-L1 were analyzed by ELISA in 73 BTC patients and 42 healthy controls. Results: Circulating levels of preoperative PD-L1 were significantly lower in patients with BTC compared to controls. Patients with low PD-L1 levels displayed a strong trend towards an impaired prognosis, and circulating PD-L1 was negatively correlated with experimental markers of promalignant tumor characteristics such as CCL1, CCL21, CCL25 and CCL26. For 37 out of 73 patients, postoperative PD-L1 levels were available. Interestingly, after tumor resection, circulating PD-L1 raised to almost normal levels. Notably, patients with further decreasing PD-L1 concentrations after surgery showed a trend towards an impaired postoperative outcome. Conclusion: Circulating PD-L1 levels were decreased in patients with resectable BTC. Lack of normalization of PD-L1 levels after surgery might identify patients at high risk for tumor recurrence or adverse outcome.

Predictors of tumor progression among children with gangliogliomas

2009 ◽  
Vol 3 (6) ◽  
pp. 461-466 ◽  
Author(s):  
Mostafa El Khashab ◽  
Lynn Gargan ◽  
Linda Margraf ◽  
Korgun Koral ◽  
Farideh Nejat ◽  
...  
Keyword(s):  
Risk Factors ◽  
Tumor Progression ◽  
Cox Regression ◽  
Tumor Resection ◽  
Progression Free Survival ◽  
Initial Presentation ◽  
Subtotal Resection ◽  
Low Grade ◽  
Cox Regression Analysis ◽  
Presenting Symptoms

Object Few reports describe the outcome and prognostic factors for children with gangliogliomas. The objective of this report was to describe the progression-free survival (PFS) for children with low-grade gangliogliomas and identify risk factors for tumor progression. Methods A retrospective study was performed in children with low-grade gangliogliomas who were evaluated and treated in the neuro-oncology department between 1986 and 2006 to determine risk factors for subsequent tumor progression. Results A total of 38 children with newly diagnosed gangliogliomas were included in this report. Thirty-four children were treated with surgery alone, 3 with subtotal resection and radiation therapy, and 1 with subtotal resection and chemotherapy. The follow-up ranged from 4 months to 15.8 years (mean 5.7 ± 4.2 years [± SD]). Seven children have experienced tumor progression, and 1 child died after his tumor subsequently underwent malignant transformation. The 5-year PFS was calculated to be 81.2% using Kaplan-Meier survival analysis. Initial presentation with seizures (p = 0.004), tumor location in the cerebral hemisphere (p = 0.020), and complete tumor resection (p = 0.035) were associated with prolonged PFS. Further analysis of the above significant variables by a Cox regression model identified initial presentation with seizures as being associated with prolonged PFS (p = 0.028). Conclusions The PFS and overall survival of children with gangliogliomas are good. Tumors located in the cerebral hemispheres, the achievement of total resection, and seizures at presentation were associated with prolonged PFS. Cox regression analysis identified presenting symptoms including seizures as significant predictive factors of PFS. Prospective studies with larger numbers of children are needed to define the significant factors of tumor progression.

Iodine-125 interstitial brachytherapy after tumor excision: an alternative eye-sparing surgery for lacrimal gland carcinoma

2021 ◽  
Author(s):  
Yang-jun Li ◽  
Ping Wang ◽  
Shao-bo Zhang ◽  
Xiao-na Ning ◽  
Chen-jun Guo ◽  
...  
Keyword(s):  
Lacrimal Gland ◽  
Tumor Recurrence ◽  
Tumor Resection ◽  
Interstitial Brachytherapy ◽  
Tumor Excision ◽  
Control Tumor ◽  
Gland Carcinoma ◽  
Iodine 125 ◽  
Good Cosmesis

Abstract Background:To describe the preliminary suppressive effects of iodine 125 brachytherapy for malignant lacrimal gland tumors after excisionMethods:The study recruit 9 patients with lacrimal gland carcinoma from May 2017 to December 2020. All patients underwent eye sparing surgical tumor resection first and then received iodine 125 interstitial brachytherapy to prevent tumor recurrence. We look over whether tumor recurred or metastasized by detecting the visual function and CT/MRI/PET MRI of every patient.Results1 patient was lost visit. The median follow up period was 29 months of other 8 patients (range, 7 43 months). One patient experienced recurrence two years later but was free from local disease after iodine 125 seeds were implanted one more time. The vision of one female patient was lost due to the seeds moving to the optic nerve. In the remaining 6 patients the vision was no changed, and CT/MRI showed no tumor was recurrencedConclusions:Permanent iodine 125 strip implantation in the orbit can be used as an alternative eye sparing surgery for malignant lacrimal gland tumors after tumor excision. It can control tumor recurrence and maintenance of vision and good cosmesis.

scholarly journals Low-grade astrocytoma: surgical outcomes in eloquent versus non-eloquent brain areas

2013 ◽  
Vol 71 (1) ◽  
pp. 31-34 ◽  
Author(s):  
André de Macedo Bianco ◽  
Flavio Key Miura ◽  
Carlos Clara ◽  
Jose Reynaldo W. Almeida ◽  
Clemar Correa da Silva ◽  
...  
Keyword(s):  
Overall Survival ◽  
Tumor Resection ◽  
Progression Free Survival ◽  
Subtotal Resection ◽  
Low Grade ◽  
Brain Areas ◽  
Free Survival ◽  
Eloquent Areas ◽  
Eloquent Area ◽  
Extent Of Surgical Resection

A retrospective study of 81 patients with low-grade astrocytoma (LGA) comparing the efficacy of aggressive versus less aggressive surgery in eloquent and non-eloquent brain areas was conducted. Extent of surgical resection was analyzed to assess overall survival (OS) and progression- free survival (PFS). Degree of tumor resection was classified as gross total resection (GTR), subtotal resection (STR) or biopsy. GTR, STR and biopsy in patients with tumors in non-eloquent areas were performed in 31, 48 and 21% subjects, whereas in patients with tumors in eloquent areas resections were 22.5, 35 and 42.5%. Overall survival was 4.7 and 1.9 years in patients with tumors in non-eloquent brain areas submitted to GTR/STR and biopsy (p=0.013), whereas overall survival among patients with tumors in eloquent area was 4.5 and 2.1 years (p=0.33). Improved outcome for adult patients with LGA is predicted by more aggressive surgery in both eloquent and non-eloquent brain areas.

Sign in / Sign up

Export Citation Format

Share Document