64 research outputs found
Soft Tissue Tumors: Aggressive angiomyxoma
Review on Soft Tissue Tumors: Aggressive angiomyxoma, with data on clinics, and the genes involved
Treatment-aware Diffusion Probabilistic Model for Longitudinal MRI Generation and Diffuse Glioma Growth Prediction
Diffuse gliomas are malignant brain tumors that grow widespread through the
brain. The complex interactions between neoplastic cells and normal tissue, as
well as the treatment-induced changes often encountered, make glioma tumor
growth modeling challenging. In this paper, we present a novel end-to-end
network capable of generating future tumor masks and realistic MRIs of how the
tumor will look at any future time points for different treatment plans. Our
approach is based on cutting-edge diffusion probabilistic models and
deep-segmentation neural networks. We included sequential multi-parametric
magnetic resonance images (MRI) and treatment information as conditioning
inputs to guide the generative diffusion process. This allows for tumor growth
estimates at any given time point. We trained the model using real-world
postoperative longitudinal MRI data with glioma tumor growth trajectories
represented as tumor segmentation maps over time. The model has demonstrated
promising performance across a range of tasks, including the generation of
high-quality synthetic MRIs with tumor masks, time-series tumor segmentations,
and uncertainty estimates. Combined with the treatment-aware generated MRIs,
the tumor growth predictions with uncertainty estimates can provide useful
information for clinical decision-making.Comment: 13 pages, 10 figures, 2 tables, 2 agls, preprints in the IEEE trans.
format for submission to IEEE-TM
MGMT promoter methylation in gliomas-assessment by pyrosequencing and quantitative methylation-specific PCR
Background
Methylation of the O6-methylguanine-DNA methyltransferase (MGMT) gene promoter is a favorable prognostic factor in glioblastoma patients. However, reported methylation frequencies vary significantly partly due to lack of consensus in the choice of analytical method.
Method
We examined 35 low- and 99 high-grade gliomas using quantitative methylation specific PCR (qMSP) and pyrosequencing. Gene expression level of MGMT was analyzed by RT-PCR.
Results
When examined by qMSP, 26% of low-grade and 37% of high-grade gliomas were found to be methylated, whereas 97% of low-grade and 55% of high-grade gliomas were found methylated by pyrosequencing. The average MGMT gene expression level was significantly lower in the group of patients with a methylated promoter independent of method used for methylation detection. Primary glioblastoma patients with a methylated MGMT promoter (as evaluated by both methylation detection methods) had approximately 5 months longer median survival compared to patients with an unmethylated promoter (log-rank test; pyrosequencing P = .02, qMSP P = .06). One third of the analyzed samples had conflicting methylation results when comparing the data from the qMSP and pyrosequencing. The overall survival analysis shows that these patients have an intermediate prognosis between the groups with concordant MGMT promoter methylation results when comparing the two methods.
Conclusion
In our opinion, MGMT promoter methylation analysis gives sufficient prognostic information to merit its inclusion in the standard management of patients with high-grade gliomas, and in this study pyrosequencing came across as the better analytical method
Sequential bortezomib and temozolomide treatment promotes immunological responses in glioblastoma patients with positive clinical outcomes: A phase 1B study
Background
Glioblastoma (GBM) is an aggressive malignant brain tumor where median survival is approximately 15 months after best available multimodal treatment. Recurrence is inevitable, largely due to O6 methylguanine DNA methyltransferase (MGMT) that renders the tumors resistant to temozolomide (TMZ). We hypothesized that pretreatment with bortezomib (BTZ) 48 hours prior to TMZ to deplete MGMT levels would be safe and tolerated by patients with recurrent GBM harboring unmethylated MGMT promoter. The secondary objective was to investigate whether 26S proteasome blockade may enhance differentiation of cytotoxic immune subsets to impact treatment responses measured by radiological criteria and clinical outcomes.
Methods
Ten patients received intravenous BTZ 1.3 mg/m2 on days 1, 4, and 7 during each 4th weekly TMZ‐chemotherapy starting on day 3 and escalated from 150 mg/m2 per oral 5 days/wk via 175 to 200 mg/m2 in cycles 1, 2, and 3, respectively. Adverse events and quality of life were evaluated by CTCAE and EQ‐5D‐5L questionnaire, and immunological biomarkers evaluated by flow cytometry and Luminex enzyme‐linked immunosorbent assay.
Results
Sequential BTZ + TMZ therapy was safe and well tolerated. Pain and performance of daily activities had greatest impact on patients' self‐reported quality of life and were inversely correlated with Karnofsky performance status. Patients segregated a priori into three groups, where group 1 displayed stable clinical symptoms and/or slower magnetic resonance imaging radiological progression, expanded CD4+ effector T‐cells that attenuated cytotoxic T‐lymphocyte associated protein‐4 and PD‐1 expression and secreted interferon γ and tumor necrosis factor α in situ and ex vivo upon stimulation with PMA/ionomycin. In contrast, rapidly progressing group 2 patients exhibited tolerised T‐cell phenotypes characterized by fourfold to sixfold higher interleukin 4 (IL‐4) and IL‐10 Th‐2 cytokines after BTZ + TMZ treatment, where group 3 patients exhibited intermediate clinical/radiological responses.
Conclusion
Sequential BTZ + TMZ treatment is safe and promotes Th1‐driven immunological responses in selected patients with improved clinical outcomes (Clinicaltrial.gov (NCT03643549)).publishedVersio
Pediatric spinal ependymomas: an unpredictable and puzzling disease. Long-term follow-up of a single consecutive institutional series of ten patients
Molecular Cytogenetic Characterization of Tenosynovial Giant Cell Tumors
Tenosynovial giant cell tumor (TSGCT) is a disease of disputed etiology and pathogenesis. Some investigations indicate a neoplastic origin of the tumors; others indicate that they are polyclonal and inflammatory. The cytogenetic and molecular genetic features of TSGCTs are largely unknown, as only some 20 localized and 30 diffuse tumors with cytogenetic aberrations have been reported. The most common karyotypic aberrations have been trisomy for chromosomes 5 and 7 and translocations involving chromosomal area 1p11-13. We decided to screen the genomes of TSGCTs by comparative genomic hybridization (CGH) to perform interphase fluorescence in situ hybridization (IP-FISH), looking for numerical aberrations of chromosomes 1, 5, and 7, and to analyze the tumors for microsatellite instability. Except for two diffuse TSGCTs that came fresh to us, and which, by karyotyping, exhibited t(1;22)(p13;q12) and a t(1;1)(q21;p11) and +7, respectively, all studies had to be performed on formalin-fixed, paraffin-embedded material. DNA was extracted from 51 localized and nine diffuse TSGCTs. CGH was successful for 24 tumors, but none of them showed copy number changes. The IP-FISH studies showed trisomy 7 in 56% of the tumors (15/27), whereas chromosomes 1 and 5 seemed to be disomic in all TSGCTs. All informative tumors were wild-type by microsatellite instability analysis
t(19;22)(q13;q12) Translocation Leading to the Novel Fusion Gene EWSRI-ZNF444 in Soft Tissue Myoepithelial Carcinoma
Myoepithelial neoplasms of soft tissue have only recently been acknowledged as a separate diagnostic entity. To know based on histological appearance whether these tumors are benign or malignant is often difficult, and their tumorigenic mechanisms remain poorly understood. We report a myoepithelial carcinoma with an aberrant near-diploid karyotype, 43 similar to 47,XX,add(1)(p34)x2,add(3)(q27)x2,del(12)(q22),+add(18)(p11)x2,del(22)(q 11),+r, found in cells cultured from a lung metastasis. The deletion in 22q led us to search by molecular cytogenetic means for possible EWSRI rearrangements, and eventually a novel chimeric gene consisting of the 5'-end of EWSRI (22q12) and the 3'-end of ZNF444 (19q13) was found. How the new fusion gene contributes to tumorigenesis is unknown, but the finding of an EWSRI rearrangement suggests that this, possibly even the EWSRI-ZNF444, is a defining pathogenetic feature of at least a subset of these tumors. (C) 2009 Wiley-Liss, Inc
Neuropsychological functioning in survivors of childhood medulloblastoma/CNS-PNET: The role of secondary medical complication
To investigate the long-term cognitive consequences of malignant pediatric brain tumor and its treatment, and factors explaining variability in cognitive functioning among survivors. Method: A geographical cohort of survivors of pediatric medulloblastoma (MB) and supratentorial primitive neuroectodermal tumor (CNS-PNET), treated between 1974 and 2013, was invited to participate. Of the 63 surviving patients, 50 (79%) consented to participation. The participants were tested with a battery of neuropsychological tests covering a wide age range. Verbal cognition, nonverbal cognition, processing speed, attention, memory, executive functioning, and manual dexterity were assessed. The participants were between 5:5 and 51:11 years of age at time of assessment. Assessments took place on average 19 years after primary tumor resective surgery. Results: One participant had a severe intellectual disability. For the rest, IQ varied from 52 to 125, with a mean score of 88.0 (SD 19.7). Twenty-eight (56%) of the participants had full-scale IQ scores in the age-average range or above. Gender, age at operation, time since operation, the presence of secondary medical complications, and treatment variables explained 46% of the variability in IQ scores, F(4,44) = 9.5, p<.001. The presence of endocrine insufficiency in combination with either epilepsy and/or hydrocephalus was associated with lowered IQ, lowered processing speed, and memory impairments. Conclusion: Patients treated for childhood MB and CNS-PNET have a lifelong risk of medical sequelae, including impaired cognitive functioning. This study adds to the literature by demonstrating the importance of following neuropsychological functioning closely, especially processing speed, learning, and memory, in survivors who have multiple secondary medical complications
Taste and smell function in long-term survivors after childhood medulloblastoma/CNS-PNET
Abstract
Purpose
To investigate taste and smell function in survivors, with a minimum of 2 years since treatment of childhood medulloblastoma (MB)/central nervous system supratentorial primitive neuroectodermal tumor (CNS-PNET).
Methods
This cross-sectional study included 40 survivors treated ≤ 20 years of age. Taste strips with four concentrations of sweet, sour, salt, and bitter were used to assess taste function in all participants. Score from 0 to 16; ≥ 9 normogeusia, < 9 hypogeusia, and complete ageusia which equals no sensation. No sensation of a specific taste quality equals ageusia of that quality. Thirty-two participants conducted smell testing using three subtests of Sniffin’ sticks: threshold, discrimination, and identification. Together they yield a TDI-score from 1 to 48; functional anosmia ≤ 16.00, hyposmia > 16.00– < 30.75, normosmia ≥ 30.75– < 41.50, and ≥ 41.50 hyperosmia. Results were compared with normative data. Survivors rated their taste and smell function using a numerical rating scale (NRS) score 0–10.
Results
Forty survivors with a mean time since treatment of 20.5 years, 13 (32.5%) were diagnosed with hypogeusia, nine (22.5%) of these being ageusic to one or more taste qualities. Seventeen (53%) of 32 participants were diagnosed with hyposmia. The mean scores of the olfactory subtests, and TDI score were significantly lower than normative data ( P < 0.0001). The mean NRS scores of smell and taste function were 7.9 ± 1.5 and 8 ± 1.3, respectively.
Conclusion
Our study showed impaired taste and smell function in survivors of childhood MB/CNS-PNET using objective measurements. However, subjective ratings did not reflect objective findings
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