A case of diffuse midline glioma,H3 K27M mutant mimicking a hemispheric malignant glioma in an elderly patient

Diffuse midline glioma, H3 K27M mutant arises from midline structures of the central nervous system and predominately affects pediatric patients. However, this disease entity was only recently established, and the clinical phenotypic spectrum remains largely unclear. We herein report a rare case of diffuse midline glioma, H3 K27M mutant with an unusual distribution in an elderly woman who presented with a diffuse glioma that invaded both sides of the thalami, and left hippocampus and frontoparietal lobes, thus mimicking a hemispheric malignant glioma. A biopsy of the lobular lesion led to a molecular diagnostic confirmation of diffuse midline glioma, H3 K27M mutant. The patient received concurrent bevacizumab and temozolomide therapy with radiation therapy and survived for 30 months. This case highlights the possibility that a glioma with cerebral hemispheric spread in an elderly patient may harbor the H3 K27M mutation.     

A juvenile case of epilepsy-associated,isocitrate dehydrogenase wild-type/histone 3 wild-type diffuse glioma with a rare BRAF A598T mutation

Here, we report a juvenile (18-year-old male) case of epilepsy-associated, isocitrate dehydrogenase wild-type/histone 3 wild-type diffuse glioma with a rare BRAF mutation and a focal atypical feature resembling diffuse astrocytoma. The patient presented with refractory temporal lobe epilepsy. Subsequently, magnetic resonance imaging revealed a hyperintense lesion in the right temporal lobe on fluid attenuated inversion recovery images. The patient underwent right lateral temporal lobectomy and amygdalohippocampectomy. Histopathologically, the tumor showed isomorphic, diffuse, infiltrative proliferation of glial tumor cells and intense CD34 immunoreactivity. The tumor cells were immunonegative for isocitrate dehydrogenase 1 (IDH1) R132H and BRAF V600E. Notably, the tumor cells showed the lack of nuclear staining for α-thalassemia/mental retardation syndrome, X-linked (ATRX). In addition, the Ki-67 labeling index, using a monoclonal antibody MIB-1, was elevated focally at tumor cells with p53 immunoreactivity. Molecular analyses identified a BRAF^A598T mutation, the first case reported in a glioma. BRAF^A598T is predicted to result in loss of kinase action; however, inactive mutants can stimulate mitogen-activated protein kinase kinase (MEK)-extracellular signal-regulated kinase (ERK) signaling through CRAF activation. Thus, according to the recent update of the consortium to inform molecular and practical approaches to central nervous system tumor taxonomy (cIMPACT-NOW update 4), our case is also compatible with diffuse glioma with the mitogen-activated protein kinase (MAPK) pathway alteration. Thorough immunohistochemical and molecular studies are necessary for diagnosis of epilepsy-associated, diffuse gliomas. Partial resemblance in histopathological and molecular genetic features to diffuse astrocytoma also calls for attention.     

Impacts of negatively charged colloidal clay particles on photoisomerization of both anionic and cationic azobenzene molecules

Although smectite-type clays are used as heterogeneous media for photofunctional guest molecules, the guest species are limited to cationic or polar molecules because of the intrinsic negative electric charges of clay particles. Nevertheless, in this study, aqueous clay colloids are reported to affect the photoisomerization kinetics of anionic and cationic azobenzene molecules dissolved in the colloids. Under UV-light irradiation, the clay colloids decelerate trans-to-cis isomerization, while under visible-light irradiation, the clay colloids accelerate cis-to-trans isomerization. In addition, the sol–gel transition of clay colloids affects the kinetics. The results considerably expand the applicability of clay colloids as matrixes for functional organic species.

Aqueous clay colloids influence the photoisomerization kinetics of both of the anionic and cationic azobenzene molecules although the guest species has been limited to cationic or polar molecules because of the intrinsic negative electric charges of the clay particles.     

Methylglyoxal Induces Inflammation,Metabolic Modulation and Oxidative Stress in Myoblast Cells

Uremic sarcopenia is a serious clinical problem associated with physical disability and increased morbidity and mortality. Methylglyoxal (MG) is a highly reactive, dicarbonyl uremic toxin that accumulates in the circulatory system in patients with chronic kidney disease (CKD) and is related to the pathology of uremic sarcopenia. The pathophysiology of uremic sarcopenia is multifactorial; however, the details remain unknown. We investigated the mechanisms of MG-induced muscle atrophy using mouse myoblast C2C12 cells, focusing on intracellular metabolism and mitochondrial injury. We found that one of the causative pathological mechanisms of uremic sarcopenia is metabolic flow change to fatty acid synthesis with MG-induced ATP shortage in myoblasts. Evaluation of cell viability revealed that MG showed toxic effects only in myoblast cells, but not in myotube cells. Expression of mRNA or protein analysis revealed that MG induces muscle atrophy, inflammation, fibrosis, and oxidative stress in myoblast cells. Target metabolomics revealed that MG induces metabolic alterations, such as a reduction in tricarboxylic acid cycle metabolites. In addition, MG induces mitochondrial morphological abnormalities in myoblasts. These changes resulted in the reduction of ATP derived from the mitochondria of myoblast cells. Our results indicate that MG is a pathogenic factor in sarcopenia in CKD.     

A patient with Alzheimer's disease complicated by elderly‐onset Cushing's syndrome who had undergone surgical treatment for adrenocorticotropic hormone‐independent macronodular adrenal hyperplasia

Cushing's syndrome (CS) is a rare disorder, especially in older people. Loss of brain volume and neurocognitive impairment of varying degrees has been demonstrated in patients with CS. However, there is a large difference between the median age of presentation of CS and that of Alzheimer's disease. We herein report a case of a patient with Alzheimer's disease complicated by elderly‐onset CS who had undergone surgical treatment for adrenal hyperplasia. Surgical correction of hypercortisolism seems to have slowed the progression of brain volume loss and cognitive dysfunction and improved psychiatric symptoms such as visual hallucination, restlessness, and psychomotor excitement. These improvements have remarkably reduced the burden on the patient's caregivers. The present case suggests that subclinical CS may be present, particularly in rapidly progressive dementia, and that surgical treatment of CS for neuropsychiatric symptoms is useful.     

Serum levels of vascular endothelial growth factor dependent on the stage progression of lung cancer

STUDY OBJECTIVE: In lung cancer, vascular endothelial growth factor (VEGF) is an important cytokine and is correlated with tumor vessel density, malignant pleural effusions, and coagulation-fibrinolysis factors in vitro. We investigated the correlation between serum VEGF level and stage progression in lung cancer to study the predicted value of VEGF level. We also studied whether coagulation-fibrinolysis factors and PaO(2) levels, which are also important factors for the prediction of the clinical course, are correlated with VEGF. METHODS: Forty-nine patients with lung cancer were investigated prospectively. VEGF levels of sera and malignant effusions, and plasma concentrations of coagulation-fibrinolysis factors were measured by enzyme-linked immunosorbent assay. We measured PaO(2) levels in all patients at rest. RESULTS: Serum levels of VEGF were increased significantly according to stage progression. Additionally, plasma concentrations of D dimer, thrombin-antithrombin complex (TAT), and tissue plasminogen activator/plasminogen activator inhibitor type I complex were elevated significantly according to stage progression. The serum VEGF level had a significant positive correlation with the TAT and D dimer levels. Serum VEGF levels had a significant negative correlation with PaO(2) levels. The incidence of cerebral vascular disorder was significantly higher in the patients with systemic hypoxemia than in those without (p<0.05). Mean VEGF levels in malignant effusions in eight patients (five with pleural effusions, two with pericardial effusions, and one with both) were extremely high, especially in pericardial effusions ([mean +/- SD] pleural effusions, 531.9+/-285.4 pg/mL; pericardial effusion, 3,071.6+/-81.3 pg/mL). CONCLUSION: We predict that in lung cancer, VEGF production and the abnormality of the coagulation-fibrinolysis system differ depending on the stage of progression of disease. Serum VEGF levels would be affected by PaO(2) levels in lung cancer.     

VAMP4 and its cognate SNAREs are required for maintaining the ribbon structure of the Golgi apparatus

Background

The Golgi apparatus is at a crossroads between anterograde and retrograde trafficking. It exhibits a twisted ribbon-like network in the juxtanuclear region of vertebrate cells. Vesicle-associated membrane protein 4 (VAMP4) is a unique v-SNARE expressed exclusively in trans-Golgi networks (TGN), where it regulates retrograde trafficking from the early endosome to the TGN with its cognate SNARE partners Syntaxin 6, Syntaxin 16, and Vti1a.

Hachimijiogan (Ba-Wei-Di-Huang-Wan), a herbal medicine,improves unbalance of calcium metabolism in aged rats

Aim of the study

Aged animals as well as elderly humans commonly exhibit calcium (Ca) shortage because of increased Ca excretion into urine and decreased intestinal Ca absorption, which induce elevation of serum PTH levels to maintain serum Ca levels between a normal physiological range. The most important organ that regulates this Ca homeostasis is the kidney. Hachimijiogan (HJG), a traditional herbal medicine in Japan and China, has been used for treating clinical diseases associated with kidney dysfunctions in elderly humans. However, the mechanisms of its pharmacological actions remain to be understood poorly. The present study was designed to examine whether HJG improves age-related unbalance of Ca metabolism at the systemic level using aged rats.

Materials and methods

HJG was administered to 21-month-old aged rats for 3 months, and several parameters associated with Ca metabolism in serum and urine were measured.

Results

Although HJG as well as aging itself did not affect serum Ca levels compared to young (11-week-old) rats, HJG improved increase in urinary Ca excretion and elevation of serum parathyroid hormone (PTH) levels in aged rats. However, HJG did not improve marked reduction of intestinal Ca absorption in aged rats.

Conclusion

HJG showed regulating action for age-related unbalance of Ca metabolism at the systemic level. This finding would provide useful information for treating age-related several disorders associated with Ca unbalance.     

Factors associated with nodal metastasis in nasopharyngeal cancer: an approach to reduce the radiation field in selected patients

Objectives

The purpose of this study was to investigate factors associated with lymph node (LN) metastasis to identify which nasopharyngeal cancer (NPC) patients can undergo a reduction in the prophylactic radiation field. MRI of biopsy-proven NPC patients was evaluated to determine primary tumour extension and the existence of LN metastasis.

Methods

Sex, age, pathological type, T stage, primary tumour size, existence beyond the midline of the nasopharynx at the primary site and parapharyngeal extension of the primary tumour were assessed regarding their impact on the laterality of LN metastasis using the χ² test.

Results

Of the 167 patients, 149 (89%) showed nodal involvement. The existence beyond the midline of the nasopharynx was significantly associated with the laterality of LN metastasis (p<0.0001). Most patients (82%) with primary tumour presence within the midline showed only ipsilateral LN metastasis or no LN metastasis. In addition, contralateral LN metastases were seen only at Level II and the retropharyngeal LN among most of other patients.

Conclusion

These results suggest that LN areas other than Level II and the retropharyngeal LN on the contralateral side could be omitted in patients with primary tumour presence within the midline and without the contralateral Level II or the retropharyngeal LN. Whether disease control is compromised by reducing the radiation field for subclinical diseases is a problem that should be solved in the future by prospective study.Most patients with nasopharyngeal cancer (NPC) show cervical lymph node (LN) metastasis at the time of diagnosis, and the frequency is reported to be approximately 90% [1-3]. Some investigators have attributed the high frequency of LN metastasis to the abundance of lymphatic tissues in the posterior wall of the nasopharynx [4, 5]. In view of this fact, the bilateral cervical LN area has usually been included in the clinical target volume (CTV) on definitive radiotherapy (RT) for NPC [6, 7]. However, while NPC may occur at any age, it has a bimodal distribution with the first peak of occurrence in the 15–25 years age range [8]. There is concern that the radiation-induced second primary cancer or late complications such as carotid artery stenosis might increase in the future with an improvement of long-term survival outcome by advancements in therapy such as intensity-modulated radiotherapy (IMRT) or a new promising chemotherapy regimen in younger generations [9-11]. Moreover, mucositis due to a wide irradiation field is still a serious problem during the period of RT, even when RT alone is performed. Thus, it should be sufficiently addressed whether the adequate coverage of the entire bilateral cervical LN area in the CTV for potential subclinical diseases is absolutely necessary for all NPC patients or not.IMRT has been increasingly used in the clinic and has shown clinical benefit in patients with head and neck cancer such as NPC. The optimal definition and the precise delineation of the CTV are absolutely necessary for IMRT, and those provide adequate coverage of the CTV while limiting the dose to the surrounding organs at risk (OAR). We have evaluated the relationship between tumour growth patterns and LN metastasis based on MRI in NPC patients [12, 13]. Our hypothesis of the current study is that if we could show the difference of frequency and regions of cervical LN metastasis according to patient and tumour characteristics, we could reduce the CTV for potential subclinical diseases in selected NPC patients. The present paper reports on the correlation between the laterality and regions of nodal metastasis and the characteristics of the patients and tumours in NPC patients by employing MRI, and pursues the possibility of the reduction of the cervical radiation field in selected patients.