Abstract Aromatic essential oils have been used in cancer treatment to enhance immunity, induce sedation, and reduce the side effects of chemotherapy. Recently, essential oils have been reported to have anti-tumor effects. We have been investigating anti-tumor aroma of essential oils as a novel treatment for glioblastoma and have found that hiba essential oil has a proliferation inhibitory effect. In this study, we investigated the antitumor effect of lemongrass essential oil for glioblastoma and its antitumor aromatherapy. Human glioblastoma cells (U87, T98G) and mouse brain tumor cells (RSV-M) were used. Lemongrass essential oil was added to each tumor cell line, and growth inhibition was observed in all cell lines. In addition, lemon grass essential oil showed growth inhibition effect when the tumor cells were separated from the oil, as was the case with direct administration, suggesting that the lemongrass essential oil components that evaporated acted on tumor cells in the surrounding area. The antitumor component of lemongrass essential oil was isolated and identified as citral, an antitumor factor, by gas chromatography. Analysis of the effects of citral showed that it strongly inhibited MARK4 activity and growth in three cell lines. The mechanism revealed that citral decreased the phosphorylation of Tau protein. MARK4 is highly expressed in glioblastoma and has been reported to be involved in cell proliferation. This study suggests a potential mechanism for citral to inhibit tumor cell proliferation via MARK4 in malignant gliomas. Citral is a volatile monoterpene and may exert its antitumor effect by evaporation diffusion. Lemongrass essential oil contains citral, which shows antitumor effects, and is expected to be applied to a new glioblastoma therapy using "aroma".
Abstract INTRODUCTION In meningioma surgery, the removal of the tumor and tumor-attached dura mater is essential. Due to its high affinity, absorbable artificial dura mater is used for the reconstruction of dural defects. In this study, we report a pathological examination of dural-like tissue in a case of meningioma that recurred at the same site after the use of absorbable artificial dura mater during initial surgery. METHOD We investigated two cases in which absorbable artificial dura mater was used for dural reconstruction during meningioma resection, and subsequently, a recurrent lesion was identified at the site of the dural reconstruction. We examined MRI images and surgical and pathological findings at the time of recurrence in these cases. RESULT All patients underwent total resection, and the pathological diagnosis was atypical meningioma. MRI images at the time of recurrence revealed multiple meningiomas along the artificial dura site. Gross findings during recurrent surgery indicated that the absorbable dura had been replaced by dura-like tissue, with the tumor also attached to the same site. Pathological findings showed bundles of fibrous tissue within the dura-like tissue, albeit with a sparser density compared to autologous dura mater. Meningioma cell invasion and angiogenesis were also observed in the dural-like tissue. DISCUSSION In all cases, multiple meningiomas were found along the dural-like tissue. This suggests that meningioma cells invading the dural-like tissue may have used it as a scaffold for meningioma recurrence. Future studies are necessary to determine the appropriateness of absorbable artificial dura mater for dural defect sites during malignant meningioma surgery.
Abstract INTRODUCTION: Brain tumor patients suffer from psychological distress and various aftereffects. Although the number of "brain tumor survivors" has been increasing due to improved outcomes of brain tumor treatment, the support system for them is inadequate in Japan. Therefore, we are examining issues affecting the QOL faced by brain tumor patients and their families, with the aim of establishing a fulfilling medical care system with a multidisciplinary approach. Here, we report on the current status of the multidisciplinary medical care system. METHODS: The EORTC QLQ-C30, 14-item resilience scale, PHQ-9, and Pittsburgh Sleep Quality Index are used to assess QOL. Based on these, an optimal care plan for brain tumor patients was developed through multidisciplinary team of professionals among physicians, nurses, clinical neuropsychologists, speech-language pathologists, occupational therapists, pharmacists, and nutritionists. A brain tumor survivorship program designed to support brain tumor patients, survivors, and care givers was developed, and this program was launched in December 2021. RESULTS AND DISCUSSION: Quality of life assessment of brain tumor patients revealed their problems and unmet needs, which enabled the development of optimal care plans in collaboration with multiple disciplines. In addition, neuropsychological approaches and cognitive behavioral therapy have been utilized as interventions for cognitive dysfunction. The Brain Tumor Survivorship Program has 18 participants as of May 31, 2023. In addition to providing online resources, patient support meetings were held virtually, providing an opportunity for participants to communicate directly with each other. CONCLUSION: We believe it is essential to establish a long-term follow-up system specifically for brain tumor patients. Through the multidisciplinary medical care system, we plan to continue to scientifically investigate and develop a support system for the various survivorship issues that brain tumor patients and their families experience across the trajectory of the illness.
Abstract INTRODUCTION Diffusion Weighted Whole Body Imaging with background body signal Suppression (DWIBS) is an imaging technique that encompasses comprehensive imaging of the entire body through diffusion-weighted imaging (DWI). In recent years, it has been increasingly utilized for investigating the etiology of fever or primary cancer. Here we present two cases of DWIBS for searching for primary cancer in patient with intracranial metastasis. CASE PRESENTATION Case1: A 60-year-old man presented with headache and diplopia and was admitted to our hospital. MRI revealed a tumor in the clivus exhibiting contrast enhancement. Endoscopic transsphenoidal surgery confirmed the diagnosis of squamous cell carcinoma. DWIBS demonstrated high intensity in a region similar to the esophagus seen on contrast-enhanced CT, leading to the diagnosis of brain metastasis from esophageal cancer. Case 2: A 50-year-old man presented with left facial paralysis and left hemiplegia and was admitted to our hospital. MRI revealed a tumor in the right middle frontal gyrus. Craniotomy confirmed the diagnosis of adenocarcinoma. Although the primary cancer remained unidentified upon initial examination, subsequent investigations revealed it originated from the lung. DWIBS showed high intensity in a region similar to the lung. DISCUSSION While FDG-PET is commonly utilized for cancer detection, its invasiveness and limitations prompt consideration of alternative modalities such as DWIBS. Recently there are some studies that have shown DWIBS to be superior to FDG PET in detecting esophageal and lung cancers. Thus, DWIBS may serve as a viable option for primary cancer screening in hospitals or communities where access to FDG PET is limited. CONCLUSION Its non-invasive nature makes DWIBS an appealing option for primary cancer detection, and further advancements are anticipated.
Abstract BACKGROUND In glioblastoma, the only chemotherapy with a clear prognostic effect is temozolomide. Research and development of novel therapies to overcome glioblastoma resistance to treatment is ongoing. We have been studying antitumor aromatherapy using aromatic compounds in aromatic essential oils as a new treatment for glioblastoma. In this study, we focus on citral, the main component of lemongrass essential oil, and report that lemongrass essential oil shows anti-tumor effects in glioma cells and mouse brain tumor models. METHODS We used human glioma cells (U251, T98G) and mouse brain tumor cells (RSV-M). We examined the proliferation ability of lemongrass in glioma cells by transpiration and direct administration. The antitumor aroma effect of lemongrass essential oil inhalation in a mouse glioma brain tumor model was evaluated by survival time analysis using the Kaplan-Meier method. RESULTS After 72 hours of incubation of tumor cells in the presence of lemongrass essential oil, U251, T98G, and RSV-M all showed anti-proliferative effects, suggesting that the transpired lemongrass essential oil components acted on tumor cells in the vicinity. Direct administration of lemongrass essential oil also inhibited cell proliferation in all glioma cells in a dose- and time-dependent manner. Then, we examined the antitumor effect of lemongrass essential oil in a mouse brain tumor model using RSV-M. The results showed that the survival period was significantly prolonged in the lemongrass essential oil-inhaled group (n=6) compared to the control group (n=6) (p=0.0102), and the cumulative survival rate was not less than 50% at the end of the study. CONCLUSION Citral is the main component of lemongrass essential oil, containing about 80%. Citral may have an antitumor effect on glioblastoma, as evidenced by its transpiration effect. In addition, its antitumor effect was also observed in animal experiments, suggesting that it could be a new treatment for glioblastoma.
Abstract Metastatic brain tumors were previously reported with prognoses of approximately 6 months. The accuracy of diagnostic imaging and advances in drug therapy have improved the treatment outcomes of various types of cancer. On the other hand, patients with advanced cancer who are detected with neurological symptoms caused by metastatic brain tumors usually face difficulty in deciding on a treatment strategy. In this study, we reported the results of cancer patients who were first detected with central nervous system symptoms in the last 10 years and treated at our hospital.There were 14 patients treated at our hospital from 2013 to 2022 with CNS symptoms as the initial symptom. The mean age was 65.5 years, and the most common primary cancer was lung cancer in 11 cases (9 NSCLC and 2 SCLC). The OS examined in the 11 lung cancer cases was 14 months. Among NSCLC, only 2 cases had EGFR mutation and no cases had ALK fusion gene. The mean Lung-molGPA was 0.89 in 9 patients with NSCLC and 0.75 in 2 patients with SCLC, and the expected survival time was 6.9 months and 2.8 months.With advances in drug therapy, median survival for patients with NSCLC brain metastases has been reported to range from 7 months to 2 years for patients with EGFR mutations and 4 years for patients with ALK fusion gene. Thus, it is necessary to consider treatment strategies according to primary tumor, histology, and genetic information, rather than considering metastatic brain tumors as a single entity.The results of this study suggest that aggressive therapeutic intervention may prolong the survival period expected at the time of initial diagnosis, even in cancer patients who are found to have metastatic brain tumors.
Abstract INTRODUCTION Aroma essential oils apply to cancer therapy because of their immune-enhancing and sedative effects, and their ability to reduce the side effects of chemotherapy. Recently, aroma essential oils have also been reported to have anti-tumor effects. We investigate the anti-tumor effects of aromatic compounds contained in essential oils as a novel treatment for glioblastoma. In this study, we analyzed the antitumor effect of lemongrass essential oil and investigated its antitumor aroma therapy for glioblastoma. methods and RESULTS Human glioblastoma cells (U87, T98G) and mouse brain tumor cells (RSV-M) were used in the study. Tumor cells were cultured in the presence of lemongrass essential oil for 72 hours, and the growth inhibitory effect was observed, suggesting that the evaporated lemongrass essential oil components acted on tumor cells in the vicinity. In addition, a similar effect was observed with citral alone, which is the main component of lemongrass. Analysis of the effects of citral revealed that citral strongly binds to MARK4 and inhibits its enzyme activity, and that citral decreases the phosphorylation of tau protein. Next, a mouse brain tumor model with RSV-M was established, and the anti-tumor effect of lemongrass essential oil was studied. The results showed that the mice that inhaled lemongrass essential oil for 12 h/day had a significantly prolonged survival period compared to the control group. DISCUSSION Citral is the main component of lemongrass essential oil, which contains 70-80% of lemongrass essential oil. This study suggests a mechanism of inhibition of tumor cell proliferation by citral in malignant gliomas. Citral is a volatile monoterpene, and its anti-tumor effect was demonstrated by diffusion through evaporation. CONCLUSION Citral in lemongrass essential oil shows anti-tumor effects and is expected to be applied to a new glioblastoma therapy using “aroma”
Abstract INTRODUCTION DWIBS is an abbreviation for Diffusion Weighted Whole Imaging with Background body signal Suppression. It is an imaging method that uses MRI diffusion-weighted imaging (DWI) to image the entire body in multiple locations and then integrates them to form a wide-area image. In recent years, MRI has been used to search for heat sources of unidentified fever and distant metastasis of cancer. In this report, we describe two cases in which DWIBS was useful in the search for the primary tumor in patients with brain metastases. CASE PRESENTATION Case 1: Male in his 60s. The patient presented with headache and diplopia, and MRI showed a neoplastic lesion in the clivus bone. A transnasal endoscopic surgery was performed, and he was diagnosed with bone metastasis of squamous cell carcinoma. Contrast-enhanced whole body CT showed similar findings, and the patient was found to have brain metastasis of esophageal cancer. Case 2: Male, 50s. He presented with a complaint of left facial paralysis and left incomplete paralysis, and a head MRI showed a brain tumor in the right middle frontal gyrus. A craniotomy was performed, and the pathological diagnosis was adenocarcinoma. A systemic search did not reveal a primary tumor, and the patient was diagnosed with cancer of unknown primary, but later lung lesions became apparent. The DWIBS performed at that time also showed a high signal at the site where lung cancer was diagnosed. DISCUSSION In Japan, MRI is widely used, and DWIBS is gradually becoming popular as a whole-body search method because it can be performed with current MRI equipment. DWIBS may be an option for primary tumor detection in facilities or regions where 18F-FDG PET is not readily available. CONCLUSION DWIBS may be useful for close examination of primary metastatic brain tumors, and more cases should be accumulated in the future.
Abstract INTRODUCTION Aromatic essential oils have antibacterial, antifungal, antiviral, anti-inflammatory, and antitumor effects. We previously investigated the antitumor effects of aromatic essential oils administered by inhalation as a novel treatment for glioblastoma. The aromatic monoterpene α-pinene, a component of many essential oils, is known to inhibit tumor growth. This study analyzed the antitumor effects of frankincense essential oil, mainly composed of α-pinene, and explored its potential for antitumor aroma therapy in glioblastoma. METHODS AND RESULTS Human glioblastoma cells (U87, T98G) and mouse brain tumor cells (RSV-M) were used. Tumor cells cultured in the presence of frankincense essential oil for 72 hours showed growth inhibition, suggesting that the evaporated components acted on nearby tumor cells. α-Pinene and limonene, the main components of frankincense, also showed similar effects alone. Inhalation studies in mice demonstrated that 30 minutes of α-pinene inhalation had the same brain transfer effect as 90 minutes. Intraperitoneal administration of α-pinene showed minimal brain transfer. For limonene, brain transfer increased with 90 minutes of inhalation compared to 30 minutes. Inhalation resulted in higher brain transfer than intraperitoneal administration. Additionally, α-pinene’s antitumor effects suggested induction of apoptosis and cell cycle arrest. DISCUSSION α-Pinene, comprising about 40% of frankincense essential oil, was found to inhibit tumor cell growth in malignant gliomas. This study suggests that α-pinene exerts antitumor effects when administered by inhalation. CONCLUSION α-Pinene in frankincense essential oil has antitumor effects and may be a novel “aroma” therapy for treating glioblastoma.
This study compared magnetic resonance imaging (MRI) findings of postmortem brain specimens with neuropathological findings to evaluate the value of postmortem MRI. Postmortem MRI was performed on five formalin-fixed whole brains with malignant tumors. Postmortem T2-weighted images detected all neuropathological abnormalities as high-signal regions but also showed histological tumor invasion in areas without edema. Tumor lesions with high necrosis and edema showed high signal intensity on T2-weighted images; in three cases, lesion enlargement was detected on the final prenatal imaging and postmortem MRI. Disease progression immediately before death may have contributed to this difference. In conclusion, the correlation between MRI and neuropathological findings facilitates understanding of the mechanisms responsible for MRI abnormalities. Increased free water due to edema, necrosis, and brain tissue injury can explain the increased signal intensity observed on T2-weighted images. Postmortem MRI may contribute to effective pathology by identifying subtle abnormalities prior to brain dissection.
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