Tuesday, January 31, 2012

[News] Birth defects in offspring of cancer survivors investigated

Survivors of childhood cancer treated with radiotherapy or chemotherapy with alkylating agents are not more likely to have children with birth defects, according to a large study by scientists working with the US-based Childhood Cancer Survivor Study.





Postado por No comments:

[News] Cancer strategy in the UK: 1 year on

At the beginning of 2011, the UK Department of Health issued Improving Outcomes: A Strategy for Cancer. The report set out the government's plans to tackle the disease in England in the coming years, including a pledge to save an additional 5000 lives per year by 2014; an ambition which, if achieved, would put the country in line with the European average for cancer survival rates.





Postado por No comments:

Monday, January 30, 2012

Mutations Tied To Aggressive Childhood Brain Tumors Revealed By Cancer Sequencing Initiative

Researchers studying a rare, lethal childhood tumor of the brainstem discovered that nearly 80 percent of the tumors have mutations in genes not previously tied to cancer. Early evidence suggests the alterations play a unique role in other aggressive pediatric brain tumors as well. The findings from the St...





Postado por No comments:

Recent advances in the molecular understanding of glioblastoma

Abstract  
Glioblastoma is the most common and most aggressive primary brain tumor. Despite maximum treatment, patients only have a median survival time of 15 months, because of the tumor's resistance to current therapeutic approaches. Thus far, methylation of the O 6-methylguanine-DNA methyltransferase (MGMT) promoter has been the only confirmed molecular predictive factor in glioblastoma. Novel "genome-wide" techniques have identified additional important molecular alterations as mutations in isocitrate dehydrogenase 1 (IDH1) and its prognostic importance. This review summarizes findings and techniques of genetic, epigenetic, transcriptional, and proteomic studies of glioblastoma. It provides the clinician with an up-to-date overview of current identified molecular alterations that should ultimately lead to new therapeutic targets and more individualized treatment approaches in glioblastoma.

  • Content Type Journal Article
  • Category Topic Review
  • Pages 1-17
  • DOI 10.1007/s11060-011-0793-0
  • Authors
    • Fonnet E. Bleeker, Department of Neurosurgery, H2 247, Neurosurgical Center Amsterdam, Location AMC, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
    • Remco J. Molenaar, Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands
    • Sieger Leenstra, Department of Neurosurgery, Erasmus Medical Center, s-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands





Postado por No comments:

Molecular and genetic profiles of radiographically defined de novo meningiomas

Abstract  
With the exception of radiation-induced tumors, benign meningiomas that are known to have developed within a defined time period are extremely rare. We have genetically characterized two cases of radiographically defined de novo, sporadic meningiomas—a 5-cm, left parasagittal tumor in a 61-year-old male and a 2.3-cm, right falx tumor in a 53-year-old female. Neither tumor was observed during MRIs performed for unrelated complaints 49 and 28 months before surgery, respectively. Both tumors were totally resected, and histopathological examination revealed WHO grade I meningiomas. In both cases, the MIB-1 staining indices were high for grade I meningioma (5.6% for case 1 and 9.1% for case 2), and abnormal accumulation of p53 were observed by immunohistochemistry. The two tumors shared losses of chromosome arms 1p and 7p by comparative genomic hybridization. The tumor suppressor merlin, product of the NF2 gene, was not detected in either tumor. These abnormalities found in common in both of the de novo meningiomas likely to play significant roles in the pathogenesis and/or rapid development of meningiomas. Moreover, taken together with previous studies, our findings indicate that the combined loss of 1p and 7p may play a critical role in the tumorigenesis of de novo, aggressive meningiomas.

  • Content Type Journal Article
  • Category Laboratory Investigation
  • Pages 1-8
  • DOI 10.1007/s11060-012-0797-4
  • Authors
    • Yohei Kitamura, Department of Neurosurgery, Keio University School of Medicine, Tokyo, Japan
    • Hikaru Sasaki, Department of Neurosurgery, Keio University School of Medicine, Tokyo, Japan
    • Kazunari Yoshida, Department of Neurosurgery, Keio University School of Medicine, Tokyo, Japan





Postado por No comments:

Thursday, January 26, 2012

Endovascular embolization of carotid-cavernous fistulas: A pioneering experience in Peru

Andres R Plasencia, Alejandro Santillan

Surgical Neurology International 2012 3(1):5-5

Background: Endovascular embolization represents the method of choice for the treatment of carotid-cavernous fistulas (CCFs). Methods: We report our experience using the endovascular technique in 24 patients harboring 25 CCFs treated between October 1994 and April 2010, with an emphasis on the role of detachable balloons for the treatment of direct CCFs. Results: Of the 16 patients who presented with direct CCFs (Barrow Type A CCFs) (age range, 7-62 years; mean age, 34.3 years), 14 were caused by traumatic injury and 2 by a ruptured internal carotid artery (ICA) aneurysm. Eight patients (age range, 32-71 years; mean age, 46.5 years) presented with nine indirect CCFs (Barrow Types B, C, and D). The clinical follow-up after endovascular treatment ranged from 2 to 108 months (mean, 35.2 months). In two cases (8%), the endovascular approach failed. Symptomatic complications related to the procedure occurred in three patients (12.5%): transient cranial nerve palsy in two patients and a permanent neurological deficit in one patient. Detachable balloons were used in 13 out of 16 (81.3%) direct CCFs and were associated with a cure rate of 92.3%. Overall, the angiographic cure rate was obtained in 22 out of 25 (88%) fistulas. Patients presenting with III nerve palsy improved gradually between 1 day and 6 months after treatment. Good clinical outcomes [modified Rankin scale (mRS) ≤ 2] were observed in 22 out of 24 (91.6%) patients at last follow-up. Conclusions: Endovascular treatment using detachable balloons still constitutes a safe and effective method to treat direct carotid-cavernous fistulas.










Postado por No comments:

Potential New Pathway Can Overcome Glioblastoma Resistance

Glioblastoma is the most prevalent and most aggressive malignant brain tumor in humans, and is one of the most resistant to current treatments. Individuals with the disease typically survive around 15 months. Earlier research concentrated on activating the (apoptosis) cell death pathway through therapeutic agents like tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)...





Postado por No comments:

Possible New Pathway Can Overcome Glioblastoma Resistance

Glioblastoma, a lethal brain cancer, is one of the most resistant to available therapies and patients typically live approximately 15 months...





Postado por No comments:

Relevance of T2 signal changes in the assessment of progression of glioblastoma according to the Res

Background: According to the Response Assessment in Neurooncology (RANO) criteria, significant nonenhancing signal increase in T2-weighted images qualifies for progression in high-grade glioma (T2-progress), even if there is no change in the contrast-enhancing tumor portion. The purpose of this retrospective study was to assess the frequency of isolated T2-progress and its predictive value on subsequent T1-progress, as determined by a T2 signal increase of 15% or 25%, respectively. The frequency of T2-progress was correlated with antiangiogenic therapy. Patients and Methods: MRI follow-up examinations (n = 777) of 144 patients with histologically proven glioblastoma were assessed for contrast-enhanced T1 and T2-weighted images. Examinations were classified as T1-progress, T2-progress with 15% or 25% T2-signal increase, stable disease, or partial or complete response. Results: Thirty-five examinations revealed exclusive T2-progress using the 15% criterion, and only 2 examinations qualified for the 25% criterion; 61.8% of the scans presenting T2-progress and 31.5% of the scans presenting stable disease revealed T1-progress in the next follow-up examination. The 2 test showed a highly significant correlation (P < .001) between T2-progress, with the 15% criterion and subsequent T1-progress. No correlation between antiangiogenic therapy and T2-progress was shown. Conclusion: Tumor progression, as determined by both contrast-enhanced T1 and T2 sequences is more frequently diagnosed than when considering only contrast-enhanced T1 sequences. Definition of T2-progress by a 15% T2-signal increase criterion is superior to a 25% criterion. The missing correlation of T2-progress and antiangiogenic therapy supports the hypothesis of T2-progress as part of the natural course of the tumor disease.






Postado por No comments:

Seizure characteristics and outcomes in 508 Chinese adult patients undergoing primary resection of l

Seizure is a common presenting manifestation and plays an important role in the clinical presentation and quality of life for patients with low-grade gliomas (LGGs). The authors set out to identify factors that influence preoperative seizure characteristics and postoperative seizure control. Cases involving adult patients who had undergone initial surgery for LGGs in a single institution between 2005 and 2009 were retrospectively reviewed. Univariate and multivariate logistic regression analyses were used to identify factors associated with preoperative seizures and postoperative seizure control. Of the 508 patients in the series, 350 (68.9%) presented with seizures. Age less than 38 years and cortical involvement of tumor were more likely to be associated with seizures (P = .003 and .001, respectively, multivariate logistic analysis). For the cohort of 350 patients with seizures, Engel classification was used to evaluate 6- and 12-month outcome after surgery: completely seizure free (Engel class I), 65.3% and 62.5%; not seizure free (Engel classes II, III, IV), 34.7% and 37.5%. After multivariate logistic analysis, favorable seizure prognosis was more common in patients with secondary generalized seizure (P = .006) and with calcification on MRI (.031). With respect to treatment-related variables, patients achieved much better seizure control after gross total resection than after subtotal resection (P < .0001). Ki67 was an independent molecular marker predicting poor seizure control in the patients with a history of seizure if overexpressed but was not a predictor for those without preoperative seizures. These factors may provide insight into developing effective treatment strategies aimed at prolonging patients' survival.






Postado por No comments:

Prognostic classification of pediatric medulloblastoma based on chromosome 17p loss, expression of M

Pediatric medulloblastoma is considered a highly heterogeneous disease and a new strategy of risk stratification to optimize therapeutic outcomes is required. We aimed to investigate a new risk-stratification approach based on expression profiles of medulloblastoma cohorts. We analyzed gene expression profiles of 30 primary medulloblastomas and detected strong evidence that poor survival outcome was significantly associated with mRNA expression profiles of 17p loss. However, it was not supported in independent cohorts from previously published data (n = 100). We speculated that this discrepancy might come from complex conditions of two important prognostic determinants: loss of tumor suppressors (chromosome 17p) and high expression of oncogenes c-myc (MYCC) or N-myc (MYCN). When patients were stratified into 5 or 7 subgroups based on simultaneous consideration of these 2 factors while defining the Wnt group as independent, obviously different survival expectancies were detected between the subgroups. For instance, predicted 5-year survival probabilities ranged from 19% to 81% in the 5 subgroups. We also found that age became a significant prognostic marker after adjusting for 17p, MYCC, and MYCN status. Diminished survival in age <3 years was more substantial in subgroups with high expression of MYCC, MYCN, or 17p loss but not in other subgroups, indicating that poor survival outcome might be synergistically affected by these 3 factors. Here we suggest a more tailored subgrouping system based on expression profiles of chromosome 17p, MYCC, and MYCN, which could provide the basis for a novel risk-stratification strategy in pediatric medulloblastoma.






Postado por No comments:

Brain tumor eradication and prolonged survival from intratumoral conversion of 5-fluorocytosine to 5

Patients with the most common and aggressive form of high-grade glioma, glioblastoma multiforme, have poor prognosis and few treatment options. In 2 immunocompetent mouse brain tumor models (CT26-BALB/c and Tu-2449-B6C3F1), we showed that a nonlytic retroviral replicating vector (Toca 511) stably delivers an optimized cytosine deaminase prodrug activating gene to the tumor lesion and leads to long-term survival after treatment with 5-fluorocytosine (5-FC). Survival benefit is dose dependent for both vector and 5-FC, and as few as 4 cycles of 5-FC dosing after Toca 511 therapy provides significant survival advantage. In the virally permissive CT26-BALB/c model, spread of Toca 511 to other tissues, particularly lymphoid tissues, is detectable by polymerase chain reaction (PCR) over a wide range of levels. In the Tu-2449-B6C3F1 model, Toca 511 PCR signal in nontumor tissues is much lower, spread is not always observed, and when observed, is mainly detected in lymphoid tissues at low levels. The difference in vector genome spread correlates with a more effective antiviral restriction element, APOBEC3, present in the B6C3F1 mice. Despite these differences, neither strain showed signs of treatment-related toxicity. These data support the concept that, in immunocompetent animals, a replicating retroviral vector carrying a prodrug activating gene (Toca 511) can spread through a tumor mass, leading to selective elimination of the tumor after prodrug administration, without local or systemic pathology. This concept is under investigation in an ongoing phase I/II clinical trial of Toca 511 in combination with 5-FC in patients with recurrent high-grade glioma (www.clinicaltrials.gov NCT01156584).






Postado por No comments:

Propentofylline decreases tumor growth in a rodent model of glioblastoma multiforme by a direct mech

Glioblastoma multiforme (GBM) is the most common and aggressive primary brain cancer, with a median survival of less than 2 years after diagnosis. The tumor microenvironment plays a critical role in tumor invasion and progression. Microglia and infiltrating macrophages are the most abundant immune cells in the tumor. In the present study, we demonstrate that systemic propentofylline (PPF), an atypical methylxanthine with central nervous system (CNS) glial modulating and anti-inflammatory actions, significantly decreased tumor growth in a CNS-1 rat model of GBM by targeting microglia and not tumor cells. Rats received tumor injections of 1 x 105 CNS-1 cells in the right striatum with daily intraperitonial injections of PPF (50 mg/kg) or saline beginning the day of tumor injection. PPF did not cause apoptosis or decrease proliferation of CNS-1 tumor cells. Furthermore, we demonstrate, using in vitro methods, that PPF decreased microglial migration toward CNS-1 tumor cells and decreased MMP-9 expression. The effects of PPF were shown to be specific to microglia and not peripheral macrophages. These results support a differential functional role of resident microglia and infiltrating macrophages in the brain tumor environment. Our data highlight microglia as a crucial target for future therapeutic development and present PPF as a possible drug for treatment of human GBM.






Postado por No comments:

Maintenance of primary tumor phenotype and genotype in glioblastoma stem cells

The clinicopathological heterogeneity of glioblastoma (GBM) and the various genetic and phenotypic subtypes in GBM stem cells (GSCs) are well described. However, the relationship between GSCs and the corresponding primary tumor from which they were isolated is poorly understood. We have established GSC-enriched neurosphere cultures from 15 newly diagnosed GBM specimens and examined the relationship between the histopathological and genomic features of GSC-derived orthotopic xenografts and those of the respective patient tumors. GSC-initiated xenografts recapitulate the distinctive cytological hallmarks and diverse histological variants associated with the corresponding patient GBM, including giant cell and gemistocytic GBM, and primitive neuroectodermal tumor (PNET)–like components. This indicates that GSCs generate tumors that preserve patient-specific disease phenotypes. The majority of GSC-derived intracerebral xenografts (11 of 15) demonstrated a highly invasive behavior crossing the midline, whereas the remainder formed discrete nodular and vascular masses. In some cases, GSC invasiveness correlated with preoperative MRI, but not with the status of PI3-kinase/Akt pathways or O6-methylguanine methyltransferase expression. Genome-wide screening by array comparative genomic hybridization and fluorescence in situ hybridization revealed that GSCs harbor unique genetic copy number aberrations. GSCs acquiring amplifications of the myc family genes represent only a minority of tumor cells within the original patient tumors. Thus, GSCs are a genetically distinct subpopulation of neoplastic cells within a GBM. These studies highlight the value of GSCs for preclinical modeling of clinically relevant, patient-specific GBM and, thus, pave the way for testing novel anti-GSC/GBM agents for personalized therapy.






Postado por No comments:

Wednesday, January 25, 2012

Possible New Pathway Can Overcome Glioblastoma Resistance

Glioblastoma, a lethal brain cancer, is one of the most resistant to available therapies and patients typically live approximately 15 months...





Postado por No comments:

Monday, January 23, 2012

Behavioural therapy is more effective than delayed treatment for persistent postprostatectomy incont

Context

Prostate cancer is the most common cancer among men, with a lifetime risk of one in six. Urinary incontinence (UI) is reported to affect 2–57% of men after radical prostatectomy.1 Patients report much higher rates of UI than doctors. The wide variation in rates may relate to different definitions of incontinence, different surgical techniques and different time points for measurement. Rates of UI are possibly higher and take longer time to resolve with advancing age. Adjuvant radiotherapy does not seem to affect long-term UI. The prevalence tends to decrease with time, probably with a peak 1–2 years after surgery.1 There are few studies that have followed men beyond 2 years. Incontinence affects quality of life and return to normal activities. It is common to offer behavioural interventions, but evidence for efficacy is inconclusive.2 Evidence for additional benefit from techniques such as...






Postado por No comments:

Oncologists should intervene

Cancer patients are often still smoking at the time of diagnosis. Cessation interventions may need to be tailored by cancer type.






Postado por No comments:

Risk of ischemia in glioma surgery: comparison of first and repeat procedures

Abstract  
The role of repeat resection in the multimodal treatment of gliomas is unclear. Repeat surgery theoretically carries a higher risk of inducing neurological deficits, which might even out any advantage of cytoreduction. We sought to determine whether the occurrence of perioperative infarction is higher for repeat surgery than for first surgery, and sought to identify factors associated with the occurrence of postoperative infarction. Therefore, we searched our database to identify patients who were operated for primary or recurrent glial tumors between October 2007 and October 2010. We analyzed 177 procedures, of which 130 (73.4%) were first surgeries and 47 (26.5%) were repeat. Initial WHO grades, KPS scores, and age were evenly distributed between the groups. Forty-six (26.0%) patients had new DWI lesions on their postoperative MRI scan. Eighteen (10.2%) patients had new lesions greater than 4 cm3. Among these were 11 (6.2%) patients, for whom the new lesion caused neurologic deficit. There was no difference between first and repeat surgery with regard to the occurrence of new DWI lesions (27.7 vs. 21.3%, P = 0.77) or neurological deficits (10.0 vs. 10.6%, P = 1.0). Tumor location in the insula, operculum, and temporal lobe was found to be significantly associated with the occurrence of new DWI lesions. We conclude that repeat surgery should not be withheld as a treatment option for patients with recurrent gliomas for fear of a higher risk of postoperative infarction or new neurologic deficit than the first surgery.

  • Content Type Journal Article
  • Category Clinical Study
  • Pages 1-9
  • DOI 10.1007/s11060-011-0784-1
  • Authors
    • Stephan Dützmann, Department of Neurosurgery, Johann Wolfgang Goethe-University, Schleusenweg 2-16, Frankfurt am Main, 60528 Frankfurt/Main, Germany
    • Florian Geßler, Department of Neurosurgery, Johann Wolfgang Goethe-University, Schleusenweg 2-16, Frankfurt am Main, 60528 Frankfurt/Main, Germany
    • Andrea Bink, Department of Neuroradiology, Johann Wolfgang Goethe-University, Schleusenweg 2-16, Frankfurt am Main, 60528 Frankfurt/Main, Germany
    • Johanna Quick, Department of Neurosurgery, Johann Wolfgang Goethe-University, Schleusenweg 2-16, Frankfurt am Main, 60528 Frankfurt/Main, Germany
    • Kea Franz, Department of Neurosurgery, Johann Wolfgang Goethe-University, Schleusenweg 2-16, Frankfurt am Main, 60528 Frankfurt/Main, Germany
    • Volker Seifert, Department of Neurosurgery, Johann Wolfgang Goethe-University, Schleusenweg 2-16, Frankfurt am Main, 60528 Frankfurt/Main, Germany
    • Christian Senft, Department of Neurosurgery, Johann Wolfgang Goethe-University, Schleusenweg 2-16, Frankfurt am Main, 60528 Frankfurt/Main, Germany





Postado por No comments:

Physiological 18F-FDG uptake by the spinal cord: is it a point of consideration for cancer patients?

Abstract  
It is essential to be familiar with normal patterns of 18F FDG distribution in the whole body for accurate PET interpretation. We assessed FDG uptake by the spinal cord to evaluate its characteristics in cancer patients. For 101 cancer patients who underwent 18F FDG PET/CT the spinal cord along its segments was visually assessed for FDG uptake, regarding MaxSUV-measurement ≥1 as cut-off point. This assessment was correlated with the patient's database variables. MRI and FDG PET-CT follow-up were included in the evaluation of positive subjects with FDG cord uptake. Forty-nine (48.5%) were positive for FDG cord uptake. The most encountered sites were the eleventh and twelfth dorsal vertebrae (36/49; 73.5%), all cervical (24/49; 49%), and the first lumbar segments (19/49; 38.7%). 38/49 (77.6%) and 11/49 (22.4%) were detected in the winter and summer, respectively (P = 0.007). MRI was available for 25 of the positive FDG cord uptake patients and showed no cord abnormalities, and in follow-up FDG PET-CT studies within 3–6 months 41/49 (83.7%) faded completely, while stationary or reduced uptake was observed for the remainder (8/49; 16.3%). FDG uptake in multiple consecutive segments of the spinal cord is not uncommon in cancer patients. This must be recognized as physiological, to avoid misdiagnosis as malignant involvement. Such physiological uptake is mostly encountered in the cervical, last two dorsal, and first lumbar levels, and quite frequently in winter.

  • Content Type Journal Article
  • Category Clinical Study
  • Pages 1-7
  • DOI 10.1007/s11060-011-0785-0
  • Authors
    • Amr Amin, Department of Nuclear Medicine, Faculty of Medicine, Cairo University, 32, Soliman Abaza St. Al-Mohandeseen, Giza, Egypt
    • Sandra J. Rosenbaum, Department of Nuclear Medicine, University of Essen, Hufelandstrasse 55, 45122 Essen, Germany
    • Andreas Bockisch, Department of Nuclear Medicine, University of Essen, Hufelandstrasse 55, 45122 Essen, Germany





Postado por No comments:

Induction of cell-cycle arrest and apoptosis in glioblastoma stem-like cells by WP1193, a novel smal

Abstract  
Glioma stem-like cells (GSCs) may be the initiating cells in glioblastoma (GBM) and contribute to the resistance of these tumors to conventional therapies. Development of novel chemotherapeutic agents and treatment approaches against GBM, especially those specifically targeting GSCs are thus necessary. In the present study, we found that a novel Janus kinase 2/Signal Transducer and Activator of Transcription 3 (JAK2/STAT3) pathway inhibitor (WP1193) significantly decreased the proliferation of established glioma cell lines in vitro and inhibit the growth of glioma in vivo. To test the efficacy of WP1193 against GSCs, we then administrated WP1193 to GSCs isolated and expanded from multiple human GBM tumors. We revealed that WP1193 suppressed phosphorylation of JAK2 and STAT3 with high potency and demonstrated a dose-dependent inhibition of proliferation and neurosphere formation of GSCs. These effects were at least due in part to G1 arrest associated with down-regulation of cyclin D1 and up-regulation of p21 Cip1/Waf-1 . Furthermore, WP1193 exposure decreased expression of stem cell markers including CD133 and c-myc, and induced cell death in GSCs through apoptosis. Taken together, our data indicate that WP1193 is a potent small molecule inhibitor of the JAK2/STAT3 pathway that shows promise as a therapeutic agent against GBM by targeting GSCs.

  • Content Type Journal Article
  • Category Laboratory Investigation
  • Pages 1-15
  • DOI 10.1007/s11060-011-0786-z
  • Authors
    • Ke Sai, Department of Neuro-Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA
    • Shuzhen Wang, Department of Neuro-Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA
    • Veerakumar Balasubramaniyan, Department of Neuro-Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA
    • Charles Conrad, Department of Neuro-Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA
    • Frederick F. Lang, Department of Neurosurgery, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA
    • Kenneth Aldape, Department of Pathology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA
    • Slawomir Szymanski, Department of Experimental Therapeutics, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA
    • Izabela Fokt, Department of Experimental Therapeutics, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA
    • Atreyi Dasgupta, Department of Neuro-Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA
    • Timothy Madden, Department of Experimental Therapeutics, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA
    • Su Guan, Department of Neuro-Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA
    • Zhongping Chen, Department of Neurosurgery/Neuro-Oncology, State Key Laboratory of Oncology in Southern China, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China
    • W. K. Alfred Yung, Department of Neuro-Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA
    • Waldemar Priebe, Department of Experimental Therapeutics, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA
    • Howard Colman, Department of Neuro-Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA





Postado por No comments:

Quantifying heterogeneity in human tumours using MRI and PET

Publication year: 2012
Source: European Journal of Cancer, Available online 19 January 2012
Marie-Claude Asselin, James P.B. O'Connor, Ronald Boellaard, Neil A. Thacker, Alan Jackson
Most tumours, even those of the same histological type and grade, demonstrate considerable biological heterogeneity. Variations in genomic subtype, growth factor expression and local microenvironmental factors can result in regional variations within individual tumours. For example, localised variations in tumour cell proliferation, cell death, metabolic activity and vascular structure will be accompanied by variations in oxygenation status, pH and drug delivery that may directly affect therapeutic response. Documenting and quantifying regional heterogeneity within the tumour requires histological or imaging techniques. There is increasing evidence that quantitative imaging biomarkers can be used in vivo to provide important, reproducible and repeatable estimates of tumoural heterogeneity.In this article we review the imaging methods available to provide appropriate biomarkers of tumour structure and function. We also discuss the significant technical issues involved in the quantitative estimation of heterogeneity and the range of descriptive metrics that can be derived. Finally, we have reviewed the existing clinical evidence that heterogeneity metrics provide additional useful information in drug discovery and development and in clinical practice.





Postado por No comments:

In Patients With Rare Brain Tumor, Abnormal Chromosome Indicator Of Treatment And Outcome

A recent analysis of clinical trial results performed by the Radiation Therapy Oncology Group (RTOG) demonstrate that a chromosomal abnormality - specifically, the absence (co-deletion) of chromosomes 1p and 19q - have definitive prognostic and predictive value for managing the treatment of adult patients with pure and mixed anaplastic oligodendrogliomas...





Postado por No comments:

Saturday, January 21, 2012

Histological analysis of the third ventricle floor in hydrocephalic and nonhydrocephalic brains: app

Journal of Neurosurgery: Pediatrics, Volume 9, Issue 2, Page 178-181, February 2012.
Object Endocrine dysfunction following endoscopic third ventriculostomy (ETV) is rare, but it has been reported. In the present study the authors sought to determine the histological nature of the floor of the third ventricle in hydrocephalic brains to better elucidate this potential association. Methods Five adult cadaveric brains with hydrocephalus were examined. Specifically, the floors of the third ventricle of these specimens were studied histologically. Age-matched controls without hydrocephalus were used for comparison. Results Although it was thinned in the hydrocephalic brains, the floor of the third ventricle had no significant difference between the numbers of neuronal cell bodies versus nonhydrocephalic brains. Conclusions Although uncommon following ETV, endocrine dysfunction has been reported. Based on the present study, this is most likely to be due to the injury of normal neuronal cell bodies found in this location, even in very thinned-out tissue.





Postado por No comments:

Navigation-guided endoscopic biopsy for pathological diagnosis for intraparenchymal pure germinoma n

Kuniyuki Onuma, Eiichi Ishikawa, Masahide Matsuda, Yasushi Shibata, Kaishi Satomi, Tetsuya Yamamoto, Alexander Zaboronok, Shingo Takano, Akira Matsumura

Surgical Neurology International 2012 3(1):9-9

Background: The authors report a case of intraparenchymal germinoma pathologically diagnosed using navigation-guided endoscopic biopsy. Case Description: A 27-year-old man had mild left hemiparesis, transcortical motor aphasia, and amnesia. Magnetic resonance (MR) imaging revealed an intraparenchymal mass lesion near the left ventricular trigone. Navigation-guided endoscopic biopsy was performed, and histopathology revealed large neoplastic cells immunohistochemically positive for germinoma-specific antigens, which were diagnosed as pure germinoma. Chemotherapy with whole-brain radiotherapy was performed, and the neurological symptoms did not change during the treatment. Follow-up MR imaging 1 year after the surgery showed no evidence of recurrence or dissemination. Conclusions: Navigation-guided endoscopic biopsy can be a useful technique in such intraparenchymal germinoma cases.





Postado por No comments:

Dermoid tumor of the lateral wall of the cavernous sinus

Rui Miguel Ferreira Rato, Lia Branco Pappamikail, Bernardo Oliveira Ratilal, Carlos Alberto Vara Luiz

Surgical Neurology International 2012 3(1):10-10

Background: Congenital intracranial dermoid tumors are very rare. The location of these dermoid lesions in the cavernous sinus and the complexity of the operative procedure for these lesions have been noted by several authors. Dermoid tumors originating in the cavernous sinus are usually interdural, and thus blurred vision is an uncommon presentation. Case Description: Herein we report the first incidental case of a cavernous sinus dermoid cyst in a 21-year-old woman. Conclusions: A literature review was done and the possible treatments and approaches for this lesion are discussed. We consider that surgical treatment is indicated in most incidental cavernous sinus dermoid lesions due to the possible symptoms related to compression or rupture leading to chemical meningitis.





Postado por No comments:

Surgical treatment of patients with vestibular schwannomas after failed previous radiosurgery

Journal of Neurosurgery, Volume 0, Issue 0, Page 1-8, Ahead of Print.
Object An increasing number of patients with vestibular schwannomas (VSs) are being treated with radiosurgery. Treatment failure or secondary regrowth after radiosurgery, however, has been observed in 2%–9% of patients. In large tumors that compress the brainstem and in patients who experience rapid neurological deterioration, surgical removal is the only reasonable management option. Methods The authors evaluated the relevance of previous radiosurgery for the outcome of surgery in a series of 28 patients with VS. The cohort was further subdivided into Group A (radiosurgery prior to surgery) and Group B (partial tumor removal followed by radiosurgery prior to current surgery). The functional and general outcomes in these 2 groups were compared with those in a control group (no previous treatment, matched characteristics). Results There were 15 patients in Group A, 13 in Group B, and 30 in the control group. The indications for surgery were sustained tumor enlargement and progression of neurological symptoms in 12 patients, sustained tumor enlargement in 15 patients, and worsening of neurological symptoms without evidence of tumor growth in 1 patient. Total tumor removal was achieved in all patients in Groups A and B and in 96.7% of those in the control group. There were no deaths in any group. Although no significant differences in the neurological morbidity or complication rates after surgery were noted, the risk of new cranial nerve deficits and CSF leakage was highest in patients in Group B. Patients who underwent previous radiosurgical treatment (Groups A and B) tended to be at higher risk of developing postoperative hematomas in the tumor bed or cerebellum. The rate of facial nerve anatomical preservation was highest in those patients who were not treated previously (93.3%) and decreased to 86.7% in the patients in Group A and to 61.5% in those in Group B. Facial nerve function at follow-up was found to correlate to the previous treatment; excellent or good function was seen in 87% of the patients from the control group, 78% of those in Group A, and 68% of those in Group B. Conclusions Complete microsurgical removal of VSs after failed radiosurgery is possible with an acceptable morbidity rate. The functional outcome, however, tends to be worse than in nontreated patients. Surgery after previous partial tumor removal and radiosurgery is most challenging and related to worse outcome.





Postado por No comments:

Growth of untreated vestibular schwannoma: a prospective study

Journal of Neurosurgery, Volume 0, Issue 0, Page 1-7, Ahead of Print.
Object Small vestibular schwannomas (VSs) are often conservatively managed and treated only upon growth. Growth is usually reported in mm/year, but describing the growth of a 3D structure by a single diameter has been questioned. As a result, VS growth dynamics should be further investigated. In addition, baseline clinical parameters that could predict growth would be helpful. In this prospective study the authors aimed to describe growth dynamics in a cohort of conservatively managed VSs. They also compared different growth models and evaluated the ability of baseline parameters to predict future growth. Methods Between 2000 and 2006, 178 consecutive patients with unilateral de novo small-sized VSs identified among the Norwegian population of 4.8 million persons were referred to a tertiary care center and were included in a study protocol of conservative management. Tumor size was defined by MR imaging–based volume estimates and was recorded along with clinical data at regular visits. Mixed-effects models were used to analyze the relationships between observations. Three growth models were compared using statistical diagnostic tests: a mm/year–based model, a cm3/year–based model, and a volume doubling time (VDT)-based model. A receiver operating characteristic curve analysis was used to determine a cutoff for the VDT-based model for distinguishing growing and nongrowing tumors. Results A mean growth rate corresponding to a VDT of 4.40 years (95% CI 3.49–5.95) was found. Other growth models in this study revealed mean growth rates of 0.66 mm/year (95% CI 0.47–0.86) and 0.19 cm3/year (95% CI 0.12–0.26). Volume doubling time was found to be the most realistic growth model. All baseline variables had p values > 0.09 for predicting growth. Conclusions Based on the actual measurements, VDT was the most correct way to describe VS growth. The authors found that a cutoff of 5.22 years provided the best value to distinguish growing from nongrowing tumors. None of the investigated baseline predictors were usable as predictors of growth.





Postado por No comments:

Friday, January 20, 2012

DNA damage-induced apoptosis: from specific DNA lesions to the DNA damage response and apoptosis

Publication year: 2012
Source: Cancer Letters, Available online 16 January 2012
Wynand P. Roos, Bernd Kaina
DNA damaging agents are potent inducers of cell death triggered by apoptosis. Since these agents induce a plethora of different DNA lesions, it is firstly important to identify the specific lesions responsible for initiating apoptosis before the apoptotic executing pathways can be elucidated. Here, we describe specific DNA lesions that have been identified as apoptosis triggers, their repair and the signaling provoked by them. We discuss simple methylating agents such as temozolomide, ionizing radiation and cisplatin, all of them are important in cancer therapy. We show that the potentially lethal events for the cell are O-methylguanine adducts that are converted by mismatch repair into DNA double-strand breaks (DSB), bulky adducts that prevent the replication of DNA and directly induced DSB following ionising radiation. Sensor systems recognizing the damage and relaying the signal via kinases to executors, which evoke a process that inhibits cell cycle progression and provokes DNA repair or, if this fails, induces apoptosis. The main DNA damage recognition factor MRN and ATM, ATR and DNA-PK, which phosphorylate a multitude of proteins and thus induce the DNA damage response (DDR), will be discussed as well as the downstream players p53, NF-kB, Akt and survivin. We review data and models describing the signaling from DNA damage to the apoptosis executing machinery and discuss the complex interplay between cell survival and death.





Postado por No comments:

PTEN in DNA damage repair

Publication year: 2012
Source: Cancer Letters, Available online 18 January 2012
Mei Ming, Yu-Ying He
The ability of DNA repair in a cell is vital to its genomic integrity and thus to the normal functioning of an organism. Phosphatase and tensin homolog (PTEN) is a well-established tumor suppressor gene that induces apoptosis and controls cell growth by inhibiting the PI3K/AKT pathway. In various human cancers, PTEN is frequently found to be mutated, deleted, or epigenetically silenced. Recent new findings have demonstrated that PTEN also plays a critical role in DNA damage repair and DNA damage response. This review summarizes the recent progress in the function of PTEN in DNA damage repair, especially in double strand break repair and nucleotide excision repair. In addition, we will discuss the role of PTEN in DNA damage response through its interaction with the Chk1 and p53 pathways. We will focus on the newly discovered mechanisms and the potential implications in cancer prevention and therapeutic intervention.





Postado por No comments:

Thursday, January 19, 2012

Key To Stopping Growth And Migration Of Brain Cancer Cells Is Cell Signaling

Brain cancer is hard to treat: it's not only strong enough to resist most chemotherapies, but also nimble enough to migrate away from radiation or surgery to regrow elsewhere. New research at the University of Colorado Cancer Center shows how to stop both. Specifically, cells signal themselves to survive, grow, reproduce, and migrate...





Postado por No comments:

Hearing Preservation Using the Middle Fossa Approach for the Treatment of Vestibular Schwannoma

BACKGROUND: The incidence of small vestibular schwannomas in patients with serviceable hearing is increasing because of the widespread use of MRI. The middle fossa approach provides the patient with an opportunity for tumor removal with hearing preservation. OBJECTIVE: To determine the rate of hearing preservation and facial nerve outcomes after removal of a vestibular schwannoma with the use of the middle fossa approach. METHODS: A retrospective case review at a tertiary, academic medical center was performed identifying patients from 1998 through 2008 that underwent removal of a vestibular schwannoma by the middle fossa approach. Preoperative and postoperative audiograms were compared to determine hearing preservation rates. In addition, facial nerve outcomes at last follow-up were recorded. RESULTS: Forty-six patients underwent a middle fossa craniotomy for the removal of a vestibular schwannoma. Of the 38 patients that had class A or class B hearing preoperatively, 24 (63.2%) retained class A or B hearing and 29 (76.3%) retained class A, B, or C hearing. When tumors were 10 mm or less in patients with class A or B preoperative hearing, 22 of 30 patients (73.3%) retained class A or B hearing. When the tumor size was greater than 10 mm in patients with class A or B preoperative hearing, 2 of 8 patients (25%) retained class A or B hearing. At most recent follow-up, 76.1% of patients had House-Brackmann grade I facial function, 13.0% had House-Brackmann grade II facial function, and 10.9% had House-Brackmann grade III facial function. CONCLUSION: Hearing preservation rates are excellent using the middle fossa approach, especially for smaller tumors. No patient experienced long-term facial nerve function worse than House-Brackmann grade III.





Postado por No comments:

Neurosurgical Management and Prognosis of Patients With Glioblastoma That Progresses During Bevacizu

BACKGROUND: The management and prognosis of glioblastoma patients after Stupp protocol treatment and progression during bevacizumab (BV) treatment remain undefined. OBJECTIVE: We compared the morbidity and survival of patients whose glioblastomas progressed during BV treatment requiring craniotomy with those of patients not treated with BV. METHODS: We retrospectively reviewed patients who underwent craniotomy for recurrent glioblastoma from 2005 to 2009. Patients operated on for progression during BV (preoperative BV) were compared with patients receiving no BV or receiving BV after surgery (postoperative BV). Patients receiving BV preoperatively were compared with those patients whose gliobastoma progressed on BV treatment but were not operated on (no surgery). RESULTS: There were 23 preoperative BV patients, 135 no BV patients, 16 postoperative BV patients, and 25 no surgery patients. Patients receiving BV preoperatively had a worse postoperative overall survival rate (hazard ratio, 3.1; P < .001) and worse postoperative progression-free survival rate (hazard ratio, 3.4, P < .001) than patients not receiving BV. Patients receiving BV preoperatively had a higher perioperative morbidity rate (44%) than patients not receiving preoperative BV (21%) (P = 0.02). Survival after diagnosis was comparable between groups (86-93 weeks, P = .9), consistent with glioblastomas developing BV evasion being not intrinsically more aggressive, but possibly BV evasion conferring a uniquely poor prognosis. No surgery patients had a shorter overall survival after progression during BV treatment compared with preoperative BV patients (hazard ratio, 3.6, P < .001). CONCLUSION: Patients whose glioblastomas progress while receiving BV leading to craniotomy exhibit shorter postoperative survival and more perioperative morbidity than patients not treated with BV. Although there may be benefits to surgical debulking, the decision to pursue repeat surgery in patients in whom BV treatment failed must be balanced against the increased risk of perioperative complications.





Postado por No comments:

Wednesday, January 18, 2012

Prognostic significance of Tks5 expression in gliomas

Publication year: 2012
Source: Journal of Clinical Neuroscience, Available online 14 January 2012
Stanley S. Stylli, Stacey T.T. I, Andrew H. Kaye, Peter Lock
A pathological hallmark of gliomas is their extensive invasion into the brain parenchyma regardless of tumour grade. Clinically this is a major factor in tumour recurrence as surgery and adjuvant therapies are unable to eradicate all the infiltrating malignant cells. Tyrosine kinase substrate with five SH3 domains (Tks5, also known as SH3PXD2A) and cortactin are required for the formation of invadopodia, actin-based protrusions of tumour cells with associated proteolytic activity implicated in tumour invasion. We investigated the prognostic significance of Tks5 and cortactin expression in 57 patients with various grades of glioma. Expression of Tks5 or cortactin occurred in all grades of tumours and expression of Tks5, but not cortactin, was associated with significantly reduced patient survival among glioma patients. This association was clearest in patients with low-grade astrocytomas and oligoastrocytomas. These results suggest a prognostic relevance for the Tks5 invadopodial protein in glial-derived brain tumours.





Postado por No comments:

Tuesday, January 17, 2012

Cancer burden in Africa and opportunities for prevention

Abstract

Cancer is an emerging public health problem in Africa. About 715,000 new cancer cases and 542,000 cancer deaths occurred in 2008 on the continent, with these numbers expected to double in the next 20 years simply because of the aging and growth of the population. Furthermore, cancers such as lung, female breast, and prostate cancers are diagnosed at much higher frequencies than in the past because of changes in lifestyle factors and detection practices associated with urbanization and economic development. Breast cancer in women and prostate cancer in men have now become the most commonly diagnosed cancers in many Sub-Saharan African countries, replacing cervical and liver cancers. In most African countries, cancer control programs and the provision of early detection and treatment services are limited despite this increasing burden. This paper reviews the current patterns of cancer in Africa and the opportunities for reducing the burden through the application of resource level interventions, including implementation of vaccinations for liver and cervical cancers, tobacco control policies for smoking-related cancers, and low-tech early detection methods for cervical cancer, as well as pain relief at the palliative stage of cancer. Cancer 2012. © 2012 American Cancer Society.






Postado por No comments:

Monday, January 16, 2012

Characterization and outcomes of optic nerve gliomas: a population-based analysis

Abstract  
Optic nerve gliomas (ONG) are rare astrocytic neoplasms. A paucity of literature exists on the epidemiology and outcomes of ONG. Here, we present a series of 445 cases of ONG obtained from the Surveillance, epidemiology and end results (SEER) database. Data on patient and tumor characteristics as well as initial treatment with surgery or radiation were extracted from the SEER Database. Survival rates were calculated using the Kaplan–Meier method. A multivariate analysis was performed to determine independent prognostic factors predicting mortality hazard ratios (HRs) using Cox proportional hazards modeling. The median age range at diagnosis was 5–9 years. Twenty percent of patients were over the age of 20 years. Amongst patients with information available on tumor grade (n = 131), 83% had a low-grade tumors and 17% had a high-grade tumors. Sixteen percent of patients received radiation therapy and 18.4% of patient underwent a sub- or gross total resection. The 5 year overall survival was 96% and 20% for patients with low- and high-grade tumors, respectively. In a multivariate analysis, grade was the only significant predictor of overall survival (HR 29.3, CI: 4.3, 205.4, P < 0.001). Age at diagnosis, receipt of radiation therapy, and extent of surgical resection were not significantly correlated with overall survival. In conclusion, ONG are rare tumors seen predominantly in children. The overall prognosis of high-grade tumors remains poor in all age groups despite multi-modality treatment.

  • Content Type Journal Article
  • Category Clinical Study
  • Pages 1-7
  • DOI 10.1007/s11060-011-0783-2
  • Authors
    • Mark V. Mishra, Department of Radiation Oncology, Jefferson Medical College, Philadelphia, PA, USA
    • David W. Andrews, Department of Neurosurgery, Jefferson Medical College, Philadelphia, PA, USA
    • Jon Glass, Department of Neurosurgery, Jefferson Medical College, Philadelphia, PA, USA
    • James J. Evans, Department of Neurosurgery, Jefferson Medical College, Philadelphia, PA, USA
    • Adam P. Dicker, Department of Radiation Oncology, Jefferson Medical College, Philadelphia, PA, USA
    • Xinglei Shen, Department of Radiation Oncology, Jefferson Medical College, Philadelphia, PA, USA
    • Yaacov Richard Lawrence, Department of Radiation Oncology, Jefferson Medical College, Philadelphia, PA, USA





Postado por No comments:

Spurious progression in pediatric brain tumors

Abstract  
In this study, we sought to characterize post-therapy MRI changes mimicking progression, which we refer to as "spurious progression" (SP) in children with brain tumors. We analyzed whether SP is associated with particular tumor types or therapeutic modalities. Between 2000 and 2009, we identified 181 consecutive children <21 years of age at our center who were treated for brain tumors and had at least three MRI scans within a year after completing therapy. SP was defined as MRI abnormalities characterized by increase in size, enhancement, edema, or cystic changes within 12 months following therapy, and stabilization or improvement on subsequent imaging. One-hundred forty-one patients with brain tumors were evaluable. Fifty-six (40%) had imaging abnormalities initially suggestive of disease progression; of these, 34 (24%) had true disease progression (TP). The remaining 22 (16%) had SP based on either stability, decrease in enhancement, edema, size, or disappearance of these cystic or non-cystic abnormalities. SP occurred in patients with low grade (n = 20) and high grade lesions (n = 2). Median time to SP was 2.4 months (range, 0.7–8.3 months), with time to stability, decrease, or disappearance at a median of 4 months (range 1.4–7.7 months). Five patients were clinically symptomatic from SP and were treated with steroids, cyst drainage, and/or surgery. Therefore, SP occurs more commonly in children with low grade tumors, but can also occur with high grade brain tumors, regardless of therapeutic approach.

  • Content Type Journal Article
  • Category Clinical Study
  • Pages 1-7
  • DOI 10.1007/s11060-011-0794-z
  • Authors
    • Sheema Chawla, Department of Radiation Oncology, University of Rochester Medical Center, 601 Elmwood Ave Box 647, Rochester, NY 14642, USA
    • David N. Korones, Department of Pediatrics, University of Rochester Medical Center, 601 Elmwood Ave Box 777, Rochester, NY 14642, USA
    • Michael T. Milano, Department of Radiation Oncology, University of Rochester Medical Center, 601 Elmwood Ave Box 647, Rochester, NY 14642, USA
    • Ali Hussain, Department of Radiology, University of Rochester Medical Center, 601 Elmwood Ave Box 648, Rochester, NY 14642, USA
    • Abdel R. Hussien, Department of Radiology, University of Rochester Medical Center, 601 Elmwood Ave Box 648, Rochester, NY 14642, USA
    • Ann G. Muhs, Department of Radiation Oncology, University of Rochester Medical Center, 601 Elmwood Ave Box 647, Rochester, NY 14642, USA
    • Manisha Mangla, Department of Radiation Oncology, University of Rochester Medical Center, 601 Elmwood Ave Box 647, Rochester, NY 14642, USA
    • Howard Silberstein, Department of Neurosurgery, University of Rochester Medical Center, 601 Elmwood Ave Box 670, Rochester, NY 14642, USA
    • Sven Ekholm, Department of Radiology, University of Rochester Medical Center, 601 Elmwood Ave Box 648, Rochester, NY 14642, USA
    • Louis S. Constine, Department of Radiation Oncology, University of Rochester Medical Center, 601 Elmwood Ave Box 647, Rochester, NY 14642, USA





Postado por No comments:

Saturday, January 14, 2012

Ocular melanoma metastasis to the cervical spine

Publication year: 2012
Source: Journal of Clinical Neuroscience, Available online 14 January 2012
Sophia F. Shakur, Ippei Takagi, Rimas V. Lukas, Steven Chmura, Thomas F. Gajewski, ...
Ocular melanoma is a rare type of malignant melanoma. Melanoma metastatic to the spine typically arises within the vertebral column, presents with back pain, and has a poor prognosis. We present a patient with a unique disease course: ocular melanoma metastasis occurred after an extended latency period of 14 years, attained a large size within the spinal intradural space, presented with severe neurological deficits without additional central nervous system disease, and the tumor was amenable to surgical intervention. We also review the literature on melanoma spine metastasis.





Postado por No comments:

A novel apoptotic mechanism of genetically engineered adenovirus-mediated tumour-specific p53 overex

Publication year: 2012
Source: European Journal of Cancer, Available online 13 January 2012
Yasumoto Yamasaki, Hiroshi Tazawa, Yuuri Hashimoto, Toru Kojima, Shinji Kuroda, ...
Oncolytic viruses engineered to replicate in tumour cells but not in normal cells could be used as tumour-specific vectors carrying the therapeutic genes. We previously developed a telomerase-specific oncolytic adenovirus, OBP-301, that causes cell death in human cancer cells with telomerase activities. Here, we further modified OBP-301 to express the wild-typep53tumour suppressor gene (OBP-702), and investigated whether OBP-702 induces stronger antitumour activity than OBP-301. The antitumour effect of OBP-702 was compared to that of OBP-301 on OBP-301-sensitive (H358 and H460) and OBP-301-resistant (T.Tn and HSC4) human cancer cells. OBP-702 suppressed the viability of both OBP-301-sensitive and OBP-301-resistant cancer cells more efficiently than OBP-301. OBP-702 caused increased apoptosis compared to OBP-301 or a replication-deficient adenovirus expressing thep53gene (Ad-p53) in H358 and T.Tn cells. Adenovirus E1A-mediated p21 and MDM2 downregulation was involved in the apoptosis caused by OBP-702. Moreover, OBP-702 significantly suppressed tumour growth in subcutaneous tumour xenograft models compared to monotherapy with OBP-301 or Ad-p53. Our data demonstrated that OBP-702 infection expressed adenovirus E1A and then inhibited p21 and MDM2 expression, which in turn efficiently induced apoptotic cell death. This novel apoptotic mechanism suggests that the p53-expressing OBP-702 is a promising antitumour reagent for human cancer and could improve the clinical outcome.





Postado por No comments:

Tuesday, January 10, 2012

Life goes on for patients with cancer, as they desire

Joshi's statement: "Adam goes clubbing, something most patients undergoing chemotherapy would not be capable of" is surprising in a review that also mentions how many patients with cancer do not want...





Postado por No comments:

Metastatic gastrointestinal stromal tumor to the thoracic and lumbar spine: first reported case and

Publication year: 2012
Source: The Spine Journal, Available online 8 January 2012
Nicholas P. Slimack, John C. Liu, Tyler Koski, Jamal McClendon, Brian A. O'Shaughnessy
Background contextMetastatic epidural spinal cord compression from gastrointestinal stromal tumors (GISTs) is a rarely reported phenomenon.PurposeTo describe the surgical management of metastatic GIST to two noncontiguous regions of the spinal column.Study designCase report.MethodsReview of the medical chart, radiographic studies, and relevant literature.ResultsThe patient underwent direct surgical decompression and stabilization of the cervicothoracic junction and the lumbar region during treatment of two distinct sites of metastatic pathology.ConclusionsTreatment of epidural compression from metastatic GIST with direct decompression and stabilization is safe and feasible.





Postado por No comments:

Monday, January 9, 2012

Epidemiology of glial and non-glial brain tumours in Europe

Publication year: 2012
Source: European Journal of Cancer, Available online 7 January 2012
Emanuele Crocetti, Annalisa Trama, Charles Stiller, Adele Caldarella, Riccardo Soffietti, ...
To the central nervous system (CNS) belong a heterogeneous group of glial and non glial rare cancers.The aim of the present study was to estimate the burden (incidence, prevalence, survival and proportion of cured) for the principal CNS cancers in Europe (EU27) and in European regions using population-based data from cancer registries participating in the RARECARE project.We analysed 44,947 rare CNS cancers diagnosed from 1995 to 2002 (with follow up at 31st December 2003): 86.0% astrocytic (24% low grade, 63% high grade and 13% glioma NOS), 6.4% oligodendroglial (74% low grade), 3.6% ependymal (85% low grade), 4.1% Embryonal tumours and 0.1% choroid plexus carcinoma. Incidence rates vary widely across European regions especially for astrocytic tumours ranging from 3/100,000 in Eastern Europe to 5/100,000 in United Kingdom and Ireland. Overall, about 27,700 new rare CNS cancers were estimated every year in EU27, for an annual incidence rate of 4.8 per 100,000 for astrocytic, 0.4 for oligodendroglial, 0.2 for ependymal and embryonal tumours and less than 0.1 for choroid plexus carcinoma.More than 154,000 persons with rare CNS were estimated alive (prevalent cases) in the EU at the beginning of 2008.Five-year relative survival was 14.5% for astrocytic tumours (42.6% for low grade, 4.9% for high grade and 17.5% for glioma NOS), 54.5% for oligodendroglial (64.9% high grade and 29.6% low grade), 74.2% for ependymal (80.4% low grade and 36.6% high grade), 62.8% for choroid plexus carcinomas and 56.8% for embryonal tumours. Survival rates for astrocytic tumours were relatively higher in Northern and Central Europe than in Eastern Europe and in UK and Ireland. The different availability of diagnostic imaging techniques and/or radiation therapy equipment across Europe may contribute to explain the reported survival differences.The estimated proportion of cured patients was 7.9% for the 'glial' group to which belong astrocytic tumours.Overall results are strongly influenced by astrocytic tumours that are the most common type.This is the first study to delineate the rare CNS cancer burden in Europe by age, sex and European region.





Postado por No comments:

Thursday, January 5, 2012

Descriptive epidemiology of malignant and nonmalignant primary spinal cord, spinal meninges, and cau

Abstract

BACKGROUND:

Primary tumors of the spinal cord, spinal meninges, and cauda equina are relatively rare, and a paucity of population-based data exist on tumors in these sites. This study intends to augment the current literature by examining incidence of these tumors on a national level.

METHODS:

Data from central cancer registries in the National Program of Cancer Registries (NPCR) and Surveillance, Epidemiology, and End Results (SEER) programs for 2004-2007 (covering 99.2% of US population) and 1999-2007 (covering 89.4% of US population) were analyzed. Analyses for diagnosis years 2004-2007 included cases of malignant and nonmalignant primary spinal cord, spinal meninges, and cauda equina tumors. Descriptive statistics including estimated age-adjusted incidence rates standardized to the 2000 US standard population were conducted for both malignant and nonmalignant primary spinal tumors from cases diagnosed during 2004-2007 as well as trend analyses on malignant cases of primary spinal tumors (n = 5103) for cases diagnosed during 1999-2007 using SEER*Stat 6.6.2 software.

RESULTS:

There were 2576 cases of malignant primary spinal tumors and 9136 cases of nonmalignant primary spinal tumors in 2004-2007. The incidence of malignant and nonmalignant primary spinal tumors combined differed by age, sex, race, and ethnicity. Results of trend analyses indicated that malignant primary spinal tumors have been stable throughout the 1999-2007 period.

CONCLUSIONS:

This large population-based study adds new insights into the descriptive epidemiology of primary spinal cord, spinal meninges, and cauda equina tumors by providing in-depth analyses of the incidence of these tumors on a national level. Cancer 2011;. © 2011 American Cancer Society.






Postado por No comments:

Outcomes after discontinuation of antiepileptic drugs after surgery in patients with low grade brain

Abstract  
Low grade tumors are associated with a high risk of seizures. Prolonged use of antiepileptic drugs (AEDs) is associated with morbidity. Determining which patients can safely discontinue AEDs perioperatively is difficult. We examined patients with low grade supratentorial brain tumors to determine characteristics of patients who underwent AED withdrawal. A retrospective chart review was performed in patients who underwent resection between 1/1/2004 and 12/31/2005 at a single center. Data were collected regarding the use of postoperative AEDs, occurrence of postoperative seizures, and patient/tumor characteristics. We examined 169 patients with a median follow-up of 3.1 years. AEDs were withdrawn or never started in 111 patients; post-withdrawal seizures occurred in 11 (9.9%). The rate was similar between meningiomas and primary brain tumors. No independent risk factors for post-withdrawal seizures were found. Of 58 patients whose AEDs were not withdrawn, postoperative seizures occurred in 28 (48%). Predictors of AED continuation included existence of preoperative seizures, temporal tumor location, tumor recurrence, incomplete resection, and male sex. The decision to continue AEDs was predictive for postoperative seizures even after controlling for known risk factors. Although clinicians are able to identify patients at high risk for postoperative seizures, treatment with AEDs is ineffective in many patients.

  • Content Type Journal Article
  • Category Clinical Study - Patient Study
  • Pages 1-6
  • DOI 10.1007/s11060-011-0779-y
  • Authors
    • Rohit R. Das, Department of Neurology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA
    • Elinor Artsy, Department of Neurology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA
    • Shelley Hurwitz, Department of Biostatistics, Brigham and Women's Hospital, Brigham Circle, 1620 Tremont Street, Boston, MA 02120-1613, USA
    • Patrick Y. Wen, Dana Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA
    • Peter Black, Department of Neurology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA
    • Alexandra Golby, Department of Neurology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA
    • Barbara Dworetzky, Department of Neurology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA
    • Jong Woo Lee, Department of Neurology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA





Postado por No comments:
Subscribe to: Posts (Atom)