Carboxylesterase Significant Lower Specific Activity of Meningiomas and Gliomas with Derived Primary Cell Culture Indicate Reduction in Anticancer Drug Metabolism | Chapter 6 | Pharmaceutical Research: Recent Advances and Trends Vol. 6

Aims: Carboxylesterases (CE) convert carboxylic esters to alcohols and carboxylic acids. CE is a protective factor in the brain cells categorized as phase-I drug-metabolizing enzymes. Therefore, our objective is to find out the different CE-specific activity of brain tumors as compared to the normal brain to understand the drug metabolism efficiency.

 

Background: Carboxylesterase activity can be influenced by interactions of a variety of compounds either directly or at the level of enzyme regulation. For e.g. drug elimination decreases and the incidence of drug-drug interactions increases when two or more drugs compete for hydrolysis by the same carboxylesterase isozyme.

 

Materials and Methods: Total Protein and Carboxylesterase assays were performed for Meningiomas and gliomas and derived primary cell culture.

 

CE spectrophotometric assays were studied for 30 meningiomas and 52 gliomas in 82 males, while 45 meningiomas and 29 gliomas in 74 female patients and derived cell culture respectively. The brain tumor protein band pattern was studied by electrophoresis.

 

Results: The brain tissue extracts for SDS PAGE displayed a highly intense single protein (not purified) band of 60 KDa in brain tumors as compared to normal brains.

 

The similar CE-specific activity exhibited between the meningiomas 20.96±5.071 (n=50) and gliomas 20.77±4.4644 nmol/min/mg (n=61) respectively showed significantly lower CE activity as compared to normal Brain (n=106) 52.355 ± 11.15 nmol/min/mg of protein and p-value was less than 0.0001 extremely statistically significant. Hence CE activities are significantly lower in all grades of parent Brain tumors as compared to normal brains. Primary cell cultures with respective passages expressed lower CE activities than parent tumors respectively. CE activity has to be determined for meningiomas by comparing them with meninges to understand the efficiency of drug metabolism. Hence Carboxyl esterase can also be made as biomarkers by developing kits for diagnosis purposes. Thus the current study promotes applications in the future by determining tumor and cell culture CE-specific activity for designing anticancer drugs for efficient metabolism and Targeting.

 

Conclusions: The current results indicate the reason for the failure of anticancer drug metabolism efficiency due to lower CE- specific activity in both meningiomas and gliomas respectively. Advanced molecular biochemistry and neuropharmacology benefit from the current study's ability to solve the drug metabolism problem in order to effectively design drug conjugates for anticancer drug metabolism by CE-specific activity and to monitor chemotherapy for anticancer drug therapeutics for future clinical applications.

 

 

Author (s) Details

Prabha Muddobalaiah
Department of Biotechnology, Ramaiah Institute of Technology, Bangalore-560054, Karnataka, India.

 

Vasanthapuram Ravi
Department of Neurovirology, NIMHANS, Bangalore, India.

 

Narayana Swamy Ramachandra Swamy
Department of Biochemistry, Central College, Bangalore University, Bangalore—560001, India.

 

Please see the book here:- https://doi.org/10.9734/bpi/prrat/v6/2204

Evaluating the Neurological Outcomes after Gamma Knife Radiosurgery for Symptomatic Skull Base Meningiomas Based on Their Locations: Single Institution Experience | Chapter 6 | Medicine and Medical Research: New Perspectives Vol. 4

Background: Meningioma is the most common primary benign intracranial tumor. Gross total resection of skull base meningioma (SBM) is so challenging due to its relevant high morbidity. Gamma knife radiosurgery is concerned, by providing a favorable therapeutic option in the management of SBM.

 

Aim: This study aims to evaluate the neurological outcome after GKRS as an adjuvant or primary treatment for SBM according to their locations.

 

Methods: This retrospective cross-sectional study consisted of 108 patients with SBM who underwent GKRS as an adjuvant or primary treatment. Patient’s medical records were collected to assess their demographic characteristics, clinical presentation, and clinical evaluations in follow-up visits. We found 40 patients with cavernous sinus meningioma (CSM), 36 patients with petroclival meningioma (PCM), and 22 patients with cerebellopontine angle meningioma (CPM). Of these, 81.1% were female (n = 90) with a median age of 52.68 years. Statistical analysis was performed using the chi-square test to evaluate the relationship between the duration of symptoms, age, gender, modality of GKRS (fractionated or not fractionated), and tumor size change on the likelihood of improvement and deterioration of neurological symptoms. The mean tumor volume was 4.5 cm3 and the mean marginal dose was 13 Gy.

 

Results: Tumor control was achieved in 96.4% of patients at a median follow-up of 38.4 months. Overall, 17 of 108 patients (15.6%) report improvement in their neurological symptoms. The majority of neurological symptoms were related to tumors which were located in the cavernous sinus 36%, Petroclival region 32.4%, and CPA 19.8%, respectively. Patients with CPM demonstrated lower rates of neurological symptom improvement compared to patients with PCM and CSM. Deterioration of neurological symptoms after GKRS developed in 11 patients (10.1%) which was more reported by patients with CSM than the others. The most improvement in cranial nerve deficit was in CN VI, V, and VIII among patients with CSM, PCM, and CPM respectively.

 

Conclusion: GKRS is acceptable as a primary or adjuvant treatment for SBM by providing an appreciable rate of improvement in neurological symptoms.

 

Author (s) Details

Farid Kazemi
Skull Base Research Center, Department of Neurosurgery, School of Medicine, Iran University of Medical Sciences, Tehran, Iran and Department of Neurosurgery, Rasool Akram Hospital, Tehran, Iran.

Parisa Javadnia
Department of Neurosurgery, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Alireza Tabibkhooei
Skull Base Research Center, Department of Neurosurgery, School of Medicine, Iran University of Medical Sciences, Tehran, Iran and Department of Neurosurgery, Rasool Akram Hospital, Tehran, Iran.

 

Mobin Naghshbandi
Student Research Center, Iran University of Medical Sciences, Tehran, Iran.

 

Vahid Ghorbani kalkha
Department of Neurosurgery, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

 

 

Please see the book here:- https://doi.org/10.9734/bpi/mmrnp/v4/1960