Medulloblastoma Presenting as Severe Headache during Pregnancy: A Case Report and Review of the Literature

Headache is a common complaint during pregnancy and the puerperium. The differentiation between a benign headache and a headache that has an underlying more endangering cause, such as an intracranial tumor, can be difficult and often requires diagnostic procedures and brain imaging techniques. We report the case of an 18-year-old female patient who developed clinical symptoms—persistent headache followed by neurological deficit—in the last part of her pregnancy. A medulloblastoma (MB) was diagnosed and treated after delivery. We review 11 other cases of MB in pregnancy reported in the literature. The most common clinical manifestation at diagnosis was headache followed by neurological deficits. We discuss the association of brain tumor growth with physiological changes during pregnancy. We conclude that clinical features of intracranial tumors can be misinterpreted as pregnancy-related symptoms and should not be dismissed.

Network Pharmacology and Inflammatory Microenvironment Strategy Approach to Finding the Potential Target of Siraitia grosvenorii (Luo Han Guo) for Glioblastoma

Background: Glioblastoma (GBM) is the most common and aggressive primary intracranial tumor of the central nervous system, and the prognosis of GBM remains a challenge using the standard methods of treatment—TMZ, radiation, and surgical resection. Traditional Chinese medicine (TCM) is a helpful complementary and alternative medicine. However, there are relatively few studies on TCM for GBM.Purpose: We aimed to find the connection between TCM and anti-GBM.Study design: Network pharmacology and inflammatory microenvironment strategy were used to predict Siraitia grosvenorii (Luo Han Guo) target for treating glioblastoma.Methods: We mainly used network pharmacology and bioinformatics.Results: CCL5 was significantly highly expressed in GBM with poor prognostics. Uni-cox and randomForest were used to determine that CCL5 was especially a biomarker in GBM. CCL5 was also the target for SG and TMZ. The active ingredient of Luo Han Guo — squalene and CCL5 —showed high binding efficiency. CCL5, a chemotactic ligand, was enriched and positively correlated in eosinophils. CCL5 was also the target of Luo Han Guo, and its effective active integrate compound –— squalene — might act on CCL5.Conclusion: SG might be a new complementary therapy of the same medicine and food, working on the target CCL5 and playing an anti-GBM effect. CCL5 might affect the immune microenvironment of GBM.

Effect of Low-dose Lidocaine on Motor Evoked Potentials in Patients Undergoing Intracranial Tumor Resection With Propofol Anesthesia

ObjectTo investigate the effect of low-dose lidocaine on motor evoked potentials (MEP) in patients undergoing intracranial tumor resection with propofol anesthesia.MethodsForty patients undergoing intracranial tumor resection and required MEP monitoring were selected.They were randomly divided into the lidocaine group (Group L, n=20) and control group (Group C, n=20) by computer generated randomization. All patients were given propofol anesthesia under the guidance of bispectral index (BIS).In Group L, lidocaine 1 mg/kg was injected intravenously during anesthesia induction. Then, lidocaine was continuously pumped at the speed of 1 mg/kg·h until the operation start. Group C was given the equal volume of normal saline. Heart rate (HR), mean artery pressure (MAP), and BIS were recorded before anesthesia induction (T0), 2 min after tracheal intubation (T1), 35 min (T2) and 50 min (T3) after anesthesia induction. The amplitude and latency of MEP at T2 and T3, the total dosage of propofol, and adverse events before T3 were recorded.ResultsCompared with Group C, HR and MAP were significantly decreased at T1 in Group L. No significant difference was observed in HR and MAP at T0, T2 and T3 between Group L and Group C. The total dosage of propofol and the incidence of adverse events were significantly lower in Group L than in Group C before T3. There was no significant difference in the amplitude and latency of MEP between the two groups at each time point.ConclusionLow-dose lidocaine has no effect on MEP in patients undergoing intracranial tumor resection. In addition, it increased hemodynamic stability, reduced propofol use, and decreased the incidence of adverse events.

Molecular profile reveals immune-associated markers of medulloblastoma for different subtypes

Background Medulloblastoma is a common intracranial tumor among children. In recent years, research on cancer genome has established four distinct subtypes of medulloblastoma: WNT, SHH, Group3, and Group4. Each subtype has its own transcriptional profile, methylation changes, and different clinical outcomes. Treatment and prognosis also vary depending on the subtype. Methods Based on the methylation data of medulloblastoma samples, methylCIBERSORT was used to evaluate the level of immune cell infiltration in medulloblastoma samples and identified 10 kinds of immune cells with different subtypes. Combined with the immune database, 293 Imm-DEGs were screened. Imm-DEGs were used to construct the co-expression network, and the key modules related to the level of differential immune cell infiltration were identified. Three immune hub genes (GAB1, ABL1, CXCR4) were identified according to the gene connectivity and the correlation with phenotype in the key modules, as well as the PPI network involved in the genes in the modules. Results The subtype marker was recognized according to the immune hub, and the subtype marker was verified in the external data set, the methylation level of immune hub gene among different subtypes was compared and analyzed, at the same time, tissue microarray was used for immunohistochemical verification, and a multi-factor regulatory network of hub gene was constructed. Conclusions Identifying subtype marker is helpful to accurately identify the subtypes of medulloblastoma patients, and can accurately evaluate the treatment and prognosis, so as to improve the overall survival of patients.

Silencing LINC00294 Restores Mitochondrial Function and Inhibits Apoptosis of Glioma Cells under Hypoxia via the miR-21-5p/CASKIN1/cAMP Axis

Glioma is a type of malignant intracranial tumor. Extensive research has identified the participation of long noncoding RNAs (lncRNAs) in glioma progression. This study investigated the mechanism of LINC00294 in mitochondrial function and glioma cell apoptosis. Glioma miRNA and mRNA microarray datasets were obtained, and differentially expressed lncRNAs in glioma were screened through various databases. The LINC00294 expression in glioma patients and glioma cells was detected. Glioma cells were treated under hypoxic conditions and transfected with LINC00294 silencing. The apoptosis and mitochondrial function of glioma cells were measured. The expressions of and relations among miR-21-5p, CASKIN1, and cAMP in glioma cells were analyzed. Under hypoxic conditions and LINC00294 silencing, the apoptosis and mitochondrial function of glioma cells were detected after inhibiting miR-21-5p or overexpressing CASKIN1. Our results indicated that LINC00294 was downregulated in glioma. LINC00294 silencing inhibited glioma cell apoptosis under hypoxia. LINC00294 silencing reversed the inhibition of hypoxia on mitochondrial function under hypoxia. LINC00294 promoted the CASKIN1 expression by sponging miR-21-5p and activated the cAMP pathway. Inhibition of miR-21-5p or overexpression of CASKIN1 annulled the effects of LINC00294 silencing on mitochondrial function and glioma cell apoptosis under hypoxia. In conclusion, LINC00294 elevated the CASKIN1 expression by sponging miR-21-5p and activating the cAMP signaling pathway, thus inhibiting mitochondrial function and facilitating glioma cell apoptosis.

The microenvironment of brain metastases from solid tumors

Brain metastasis (BrM) is an area of unmet medical need that poses unique therapeutic challenges and heralds a dismal prognosis. The intracranial tumor microenvironment (TME) presents several challenges, including the therapy-resistant blood–brain barrier, a unique immune milieu, distinct intercellular interactions, and specific metabolic conditions, that are responsible for treatment failures and poor clinical outcomes. There is a complex interplay between malignant cells that metastasize to the central nervous system (CNS) and the native TME. Cancer cells take advantage of vascular, neuronal, immune, and anatomical vulnerabilities to proliferate with mechanisms specific to the CNS. In this review, we discuss unique aspects of the TME in the context of brain metastases and pathways through which the TME may hold the key to the discovery of new and effective therapies for patients with BrM.

632 Toripalimab combined with platinum-based chemotherapy as a second-line treatment for small cell lung cancer (SCLC) with brain metastases: a case report

BackgroundImmunotherapy targeting PD-L1 together with platinum-based chemotherapy has demonstrated clinical activity in extensive-stage small cell lung cancer (ES-SCLC). However, brain metastasis seems to be an adverse prognostic factor. Here we report a case of a pretreated ES-SCLC patient with brain metastases who obtained marked clinical benefit from a combination of the anti-PD-1 antibody (toripalimab) together with platinum-based chemotherapy.MethodsA 56-year-old male smoker first presented at our hospital on March 17, 2018, with a dull pain in the right chest wall, without obvious cause. The patient underwent a biopsy of the right lung, revealing small cell carcinoma. Between April 20, 2018 and June 27, 2018, the patient received four cycles of platinum-based chemotherapy (irinotecan with carboplatin) and achieved a partial response (PR) (RECIST 1.1). However, at the end of 2019, his condition began to deteriorate. He had left upper abdominal pain without obvious cause, followed by dizziness, headache, unsteady walking, dull pain in the middle and upper abdomen, accompanied by acid regurgitation and belching. CT and MRI showed secondary malignant tumors in the liver, intracranially and in the pancreas with lymph node metastasis. Because the patient refused radiotherapy, from June 2020 he was treated with etoposide (160 mg, every 3 weeks on day 1–3) plus cisplatin (40 mg, every 3 weeks on day 1–3) combined with toripalimab (240 mg, every 3 weeks on day 1).ResultsFollowing two cycles of treatment, MRI showed significant shrinkage of the patient's intracranial tumor. After the next sequential 4 cycles of therapy, MRI showed that the intracranial tumor had almost disappeared, CT images showed similar shrinkage of the liver and pancreas tumors. The overall efficacy assessment was PR. The patient tolerated the treatment with no side effects and is experiencing a durable clinical benefit. He now maintains immunotherapy and leads a normal life with no progression at the latest follow up on June 2021.ConclusionsImmunotherapy targeting PD-L1 added to platinum-based chemotherapy has been shown to prolong overall survival in ES-SCLC patients. Even in pretreated patients with brain metastases, PD-1 inhibitors plus platinum-based chemotherapy may also play a potential role. This is worthy of further investigation in formal clinical trials.