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1.
J Neurol Surg Rep ; 81(1): e10-e14, 2020 Jan.
Article in English | MEDLINE | ID: mdl-32257763

ABSTRACT

Background Meningioma accounts for more than 35% of all diagnosed brain tumors of the central nervous system and, moreover, it is the most common benign recipient of tumor-to-tumor metastasis. Several cases with tumor-to-meningioma metastasis by breast, lung, and intestinal cancer have been described before. Case description The case of a patient with a longstanding history of multiple meningiomas ( n = 4) that suddenly became symptomatic and progressive in size is presented. Following extirpation of the two largest meningiomas, a histological examination revealed two separate tumor-to-meningioma metastases of clear cell renal cell carcinoma that was undiagnosed before. Post-surgical computed tomography scan then confirmed tumor-suspect lesions in both kidneys. After recovery and rehabilitation, adjuvant radio-chemo-therapy was applied according to protocols for kidney cancer. No other tumor-to-tumor-suspect event occurred since then for the remaining two meningiomas. Conclusion Review of literature and our case strengthens the idea of meningioma as a favorable premetastatic niche. Considering that the patient lived with a stable disease for many years, a sudden progress of tumor size in association with neurological deterioration was highly suspected for malign involvement, including the possibility of tumor-to-tumor metastasis. Physicians should be aware about this phenomenon and treat patients accordingly to the underlying disease.

2.
Acta Neurochir (Wien) ; 162(2): 417-425, 2020 02.
Article in English | MEDLINE | ID: mdl-31736002

ABSTRACT

BACKGROUND: IDH-wild-type glioblastoma (GBM) is a disease with devastating prognosis. First-line therapy consists of gross total resection and adjuvant radiotherapy with concomitant temozolomide. Several clinical parameters have been identified to provide prognostic value. We investigated whether peri-operative overall neurological performance could also be used to evaluate patients' prognosis. METHODS: All patients with histologically diagnosed GBM between 2014 and 2017 over 18 years and MRI within 72 h after surgery were reviewed. To quantify neurological performance, the medical research council neurological performance score (MRC-NPS) was used. Univariate analysis with Kaplan-Meier estimate and log-rank test was performed. Survival prediction and multivariate analysis were performed employing Cox proportional hazard regression. RESULTS: One hundred thirty-nine patients were included. In univariate analysis, survival decreased with increasing post-operative MRC-NPS scale. Moreover, post-operative MRC-NPS of 4 was statistically significant associated with reduced overall survival when analyzed for complete (p = 0.027) and partial resection (p = 0.002) as well as unilobar (p = 0.003) and multilobar tumor location (p < 0.0005). In multivariate analysis, extent of resection (hazard ratio (HR) 3.142), adjuvant therapy regimen (HR 3.001), tumor location (HR 2.005), and post-operative MRC-NPS (HR 2.310) had significant influence on overall survival. CONCLUSION: We propose the post-operative neurological performance as an independent prognostic factor for GBM patients.


Subject(s)
Brain Neoplasms/surgery , Glioblastoma/surgery , Postoperative Complications/epidemiology , Adult , Aged , Brain Neoplasms/diagnosis , Brain Neoplasms/epidemiology , Female , Glioblastoma/diagnosis , Glioblastoma/epidemiology , Humans , Male , Middle Aged , Neurosurgical Procedures/adverse effects , Postoperative Complications/diagnosis , Survival Analysis
3.
Future Oncol ; 15(32): 3683-3691, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31664860

ABSTRACT

Aim: The naturally occurring dipeptide carnosine (CAR) has been considered for glioblastoma therapy. As CAR also protects against ionizing irradiation (IR), we investigated whether it may counteract standard therapy consisting of postsurgery IR and treatment with temozolomide (TMZ). Materials & methods: Four isocitrate dehydrogenase-wildtype primary cell cultures were exposed to different doses of IR and different concentrations of TMZ and CAR. After exposure, viability under the different conditions and combinations of them was determined. Results: All cultures responded to treatment with TMZ and IR with reduced viability. CAR further decreased viability when TMZ and IR were combined. Conclusion: Treatment with CAR does not counteract glioblastoma standard therapy. As the dipeptide also protects nontumor cells from IR, it may reduce deleterious side effects of treatment.


Subject(s)
Antineoplastic Agents, Alkylating/pharmacology , Brain Neoplasms/pathology , Carnosine/pharmacology , Cell Survival/drug effects , Glioblastoma/pathology , Isocitrate Dehydrogenase/genetics , Radiation, Ionizing , Temozolomide/pharmacology , Aged , Brain Neoplasms/genetics , Brain Neoplasms/therapy , Cell Survival/radiation effects , Female , Glioblastoma/genetics , Glioblastoma/therapy , Humans , Isocitrate Dehydrogenase/metabolism , Male , Middle Aged , Tumor Cells, Cultured
4.
Cancer Chemother Pharmacol ; 83(6): 1017-1024, 2019 06.
Article in English | MEDLINE | ID: mdl-30888463

ABSTRACT

PURPOSE: Glioblastoma (GBM) is the most common malignant tumor of the central nervous system. Median survival of glioblastoma patients under standard therapy including radiotherapy and chemotherapy using temozolomide (TMZ) is 14.6 months. As cell culture experiments combining D,L-methadone with doxorubicin demonstrated an increased reduction of cell viability of glioblastoma cells, the opioid has been discussed as a drug for the treatment of GBM. Despite lack of clinical and experimental evidence that D,L-methadone in combination with standard therapy will be beneficial, an increasing number of tumor patients medicating themselves with D,L-methadone present to the hospitals in Germany. METHODS: As a first step towards understanding whether D,L-methadone may increase the efficacy of standard therapy, we used a cell culture model of primary GBM and fibroblast cell cultures derived from GBM patients. The cultures were treated with different concentrations of D,L-methadone in combination with X-irradiation, TMZ or both. Cell viability was determined by measuring ATP in cell lysates and dehydrogenase activity in living cells. RESULTS: When only treated with D,L-methadone, 1 µM of the opioid was sufficient to reduce viability of fibroblasts, whereas 10 µM was needed to significantly reduce glioblastoma cell viability. In addition, D,L-methadone did not improve the anti-neoplastic effects of X-irradiation, temozolomide or both. CONCLUSIONS: As D,L-methadone reduces glioblastoma cell viability only when concentrations are used that had been reported to be toxic to patients and as there were no interactions observable combining it with standard therapy, a recommendation for the use of D,L-methadone in glioblastoma therapy cannot be given.


Subject(s)
Analgesics, Opioid/pharmacology , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Brain Neoplasms/therapy , Glioblastoma/therapy , Methadone/pharmacology , Adult , Aged , Analgesics, Opioid/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Cell Survival/drug effects , Doxorubicin/administration & dosage , Female , Humans , In Vitro Techniques , Male , Methadone/administration & dosage , Middle Aged , Temozolomide/administration & dosage
5.
Cancer Cell Int ; 18: 111, 2018.
Article in English | MEDLINE | ID: mdl-30123089

ABSTRACT

BACKGROUND: Glioblastoma (GBM) is a tumor of the central nervous system. After surgical removal and standard therapy, recurrence of tumors is observed within 6-9 months because of the high migratory behavior and the infiltrative growth of cells. Here, we investigated whether carnosine (ß-alanine-l-histidine), which has an inhibitory effect on glioblastoma proliferation, may on the opposite promote invasion as proposed by the so-called "go-or-grow concept". METHODS: Cell viability of nine patient derived primary (isocitrate dehydrogenase wildtype; IDH1R132H non mutant) glioblastoma cell cultures and of eleven patient derived fibroblast cultures was determined by measuring ATP in cell lysates and dehydrogenase activity after incubation with 0, 50 or 75 mM carnosine for 48 h. Using the glioblastoma cell line T98G, patient derived glioblastoma cells and fibroblasts, a co-culture model was developed using 12 well plates and cloning rings, placing glioblastoma cells inside and fibroblasts outside the ring. After cultivation in the presence of carnosine, the number of colonies and the size of the tumor cell occupied area were determined. RESULTS: In 48 h single cultures of fibroblasts and tumor cells, 50 and 75 mM carnosine reduced ATP in cell lysates and dehydrogenase activity when compared to the corresponding untreated control cells. Co-culture experiments revealed that after 4 week exposure to carnosine the number of T98G tumor cell colonies within the fibroblast layer and the area occupied by tumor cells was reduced with increasing concentrations of carnosine. Although primary cultured tumor cells did not form colonies in the absence of carnosine, they were eliminated from the co-culture by cell death and did not build colonies under the influence of carnosine, whereas fibroblasts survived and were healthy. CONCLUSIONS: Our results demonstrate that the anti-proliferative effect of carnosine is not accompanied by an induction of cell migration. Instead, the dipeptide is able to prevent colony formation and selectively eliminates tumor cells in a co-culture with fibroblasts.

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