Cytopathology of Chondromyxoid Fibroma: Report of 2 Cases with Immunocytochemical Expression of GRM1.

INTRODUCTION: Chondromyxoid fibroma (CMF) is a rare, benign bone tumor that occurs predominantly in the second and third decades of life, more frequently in males. Overexpression of GRM1 as a consequence of tumor-specific gene rearrangement of GRM1 has recently been reported as a useful immunohistochemical marker for histopathological diagnosis of CMF. However, the usefulness of GRM1 staining of cytology specimens has not yet been evaluated. In this report, the cytological findings and GRM1 immunocytochemistry of two cases of CMF are described. CASE PRESENTATIONS: Case 1 was a 15-year-old girl with a rib tumor. Imaging findings suggested a benign neurogenic tumor such as schwannoma. The tumor had increased in size over a 2-year period and was resected. Case 2 was a 14-year-old boy with a metatarsal tumor involving his left first toe. Imaging findings were suspicious of a benign neoplastic lesion. Biopsy findings suggested a benign tumor, and the patient underwent tumor resection. Cytologically, in both cases the tumor cells were predominantly spindle-shaped or stellate, with a myxoid to chondromyxoid background matrix and multinucleated giant cells, and these matrices were metachromatic with Giemsa staining. Cellular atypia was more accentuated in case 2 than in case 1. Immunocytochemical staining for GRM1 was positive in both cases. CONCLUSION: Due to the overlap in cytological findings, it is often difficult to differentiate CMF from chondroblastoma and chondrosarcoma grade 2. Immunocytochemical staining for GRM1 may support the diagnosis of CMF, and the reuse of Papanicolaou-stained specimens is applicable. The present cases further demonstrated the difficulty of differentiating CMF from other mimicking tumors such as chondroblastoma and chondrosarcoma grade 2. In such instances, immunocytochemistry for GRM1 is applicable to the diagnostic process, the value of which is strengthened by reusing Papanicolaou-stained specimens.

A Case of Fibula Regeneration after Below-the-knee Amputation in an Adult.

We report the case of an adult with fibula regeneration after below-the-knee amputation. Fibula regeneration conventionally occurs at the donor site of children after autogenous fibula transplantation when the periosteum is preserved. However, the patient was an adult, and the regenerated fibula was 7-cm long and grew directly from the stump. A 47-year-old man was referred to the plastic surgery department owing to stump pain. He had an open comminuted fracture of the right fibula and tibia due to a traffic accident when he was 44 years old and underwent below-the-knee amputation and negative pressure wound therapy for skin defects. The patient recovered and was able to walk using a prosthetic limb. Upon radiography, the fibula was found to have regenerated 7 cm directly from the stump. Pathological examination revealed that the regenerated fibula contained normal bone tissue and neurovascular bundles in the cortex. The periosteum, mechanical stimuli with limb proteases, and negative pressure wound therapy were suspected to have accelerated bone regeneration. He had no inhibitory factors for bone regeneration, including diabetes mellitus, peripheral arterial disease, or active smoking status. After the resection of the regenerated fibula, the patient was ambulatory without further bone regeneration or pain. This case report suggests that bone regeneration may occur even in adults. The surgeon should not leave any part of the periosteum behind in patients undergoing amputation. In adult amputees complaining of stump pain, the possibility of bone regeneration may be considered.

Chlamydia Peritonitis Mimicking Juvenile Carcinomatous Peritonitis Diagnosed by Exploratory Laparoscopy: A Case Report.

Chlamydia trachomatis infections may occur in multiple organs, including the lungs, lymph nodes, peritoneal cavity, and genitourinary systems. This disease results in significant ascites, the swelling of lymph nodes, and elevated tumor markers (CA125), sometimes mimicking an ovarian malignancy. At our hospital, we often perform examination laparoscopic surgery in cases of suspected gynecologic cancers before initial treatment. In this paper, we report the case of a 19-year-old woman who came to our hospital because of an ovarian tumor and ascites. There was no history of sexual intercourse (self-reported). We suspected ovarian cancer from image inspections, so we performed laparoscopic surgery for diagnosis. The final pathological diagnosis was acute-to-chronic inflammation of the bilateral fallopian tubes, and a cytologic examination of the ascites was negative for malignant cells. The C. trachomatis antigen was positive on vaginal examination after the operation. Based on this result, we diagnosed this patient with C. trachomatis infection. Chlamydia peritonitis should be a differential diagnosis for cancer peritonitis in juvenile patients with abnormal ascites. Exploratory laparoscopy should help confirm the pathological diagnosis.

Immune profile analysis of peripheral blood and tumors of lung cancer patients treated with immune checkpoint inhibitors.

Background: Immune checkpoint inhibitors (ICIs) have become central to lung cancer drug therapy, and establishing biomarkers that can predict effects and adverse events (AEs) is awaited. We prospectively analyzed the association between the immune-related molecular expression in peripheral blood mononuclear cells (PBMCs) and lung cancer tissues, and the effects of ICI monotherapy. Methods: Twenty-one patients with advanced non-small cell lung cancer (NSCLC) who received ICI monotherapy were included. Changes in the expression of immune-related molecules in PBMCs before and after the administration of ICI were analyzed by flow cytometry. The major histocompatibility complex (MHC) class I and programmed cell death-ligand 1 (PD-L1) expression of cancer cells, and the PD-L1, CD8 and CD103 expression of tumor infiltrating immune cells in lung cancer tissue before the administration of ICI were confirmed by immunohistochemistry (IHC). Results: Twenty-one patients were investigated, including 11 adenocarcinoma and 10 squamous cell carcinoma cases. Anti-programmed cell death protein-1 (PD-1) antibody (n=18) and anti-PD-L1 antibody (n=3) were administered. The clinical responses were graded as follows: complete response (CR) (n=1), partial response (PR) (n=7), stable disease (SD) (n=10) and progressive disease (PD) (n=3). Among immune-related molecules expressed in PBMCs, the CD103+ CD39+ CD8+ T cell change after administration closely correlated with the clinical response. In the univariate analyses of the factors associated with progression-free survival (PFS), CD103+ CD39+ CD8+ cell change after administration was identified as a significant prognostic factor, while the CD103+ CD39+ CD8+ cell change after administration and Brinkman index were independent prognostic factors in a multivariate analysis of the factors associated with PFS. Conclusions: The CD103+ CD39+ CD8+ cell change after administration may predict the efficacy of ICIs.

[Giant Anastomotic Aneurysm Associated with Albumin/Glutaraldehyde Sealant as a Late Complication after Acute Aortic Dissection Surgery:Report of a Case].

A 74-year-old woman was taken to our hospital with a chief complaint of chest and back pain. She was diagnosed with Stanford type A acute aortic dissection and underwent ascending aortic replacement. Fifteen months after surgery, a giant anastomotic aneurysm was found at the proximal and distal anastomoses on chest computed tomography (CT), and reoperation was indicated. Following sternal re-entry, anastomotic dehiscence was found where BioGlue, albumin/glutaraldehyde sealant, had been applied during the previous surgery, and caused aneurysm. Severe postoperative adhesion precluded extensive surgery, and redo replacement of the ascending aorta was carried out. Histopathological examination revealed extensive necrosis of smooth muscle cells in the aortic wall at the anastomotic site and a marked inflammatory cell infiltration around the aortic wall and the artificial graft, and association of BioGlue use was suggested. The use of appropriate tissue adhesives to reinforce the dissected aortic wall is important, as well as careful long-term follow-up.

Plasma exosomal DOK3 reflects immunological states in lung tumor and predicts prognosis of gefitinib treatment.

To identify liquid biomarkers that predict clinical outcomes of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), we enrolled patients with EGFR gene mutation-positive non-small-cell lung cancer who were intended to receive gefitinib treatment. Using plasma samples obtained prior to gefitinib treatment from 12 enrolled patients, we performed comprehensive proteomic analysis of plasma exosomes to explore proteins correlating with tumor reduction rate (TRR), progression-free survival (PFS), or overall survival (OS). Of the detected 1769 proteins, 119, 130, or 119 proteins demonstrated a strong correlation (|r| > 0.5) with TRR, PFS, or OS, respectively. Interestingly, 34 (29%), 41 (32%), or 27 (23%) of them, respectively, were functionally involved in the regulation of the immune response. CD8α chain was consistently listed as a molecule positively correlated with PFS and OS, suggesting that the long-lasting effects of gefitinib may be due to the antitumor effects of CD8+ T cells, as well as the induction of immunogenic apoptosis of tumor cells by blocking the EGFR signaling pathway. Notably, Doking Protein 3 (DOK3), a molecule involved in B-cell receptor signaling, and some immunoglobulin and complement molecules exhibited a clear correlation with PFS longevity of gefitinib treatment. Indeed, the strong expression of DOK3 in B cells was confirmed within tertiary lymphoid structures of lung cancer tissues derived from patients with long PFS. These findings suggest that the patients with active B-cell and T-cell immunity as a host immunological feature are more likely to benefit from gefitinib therapy. Circulating exosomal DOK3 has the potential as a predictive marker of response to gefitinib indicating this immunological feature.

Potential inhibitory effects of low-dose thoron inhalation and ascorbic acid administration on alcohol-induced hepatopathy in mice.

Although thoron inhalation exerts antioxidative effects in several organs, there are no reports on whether it inhibits oxidative stress-induced damage. In this study, we examined the combined effects of thoron inhalation and ascorbic acid (AA) administration on alcohol-induced liver damage. Mice were subjected to thoron inhalation at 500 or 2000 Bq/m3 and were administered 50% ethanol (alcohol) and 300 mg/kg AA. Results showed that although alcohol administration increased the levels of glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) in the serum, the combination of thoron inhalation (500 Bq/m3) and AA administration 24 h after alcohol administration effectively inhibited alcohol-induced liver damage. The combination of thoron inhalation (500 Bq/m3) and AA administration 24 h after alcohol administration increased catalase (CAT) activity. Alcohol administration significantly decreased glutathione (GSH) levels in the liver. The GSH content in the liver after 2000 Bq/m3 thoron inhalation was lower than that after 500 Bq/m3 thoron inhalation. These findings suggest that the combination of thoron inhalation at 500 Bq/m3 and AA administration has positive effects on the recovery from alcohol-induced liver damage. The results also suggested that thoron inhalation at 500 Bq/m3 was more effective than that at 2000 Bq/m3, possibly because of the decrease in GSH content in the liver. In conclusion, the combination of thoron inhalation at 500 Bq/m3 and AA administration promoted an early recovery from alcohol-induced liver damage.

Radon Solubility and Diffusion in the Skin Surface Layer.

In specific situations such as bathing in a radon spa, where the radon activity concentration in thermal water is far higher than that in air, it has been revealed that radon uptake via skin can occur and should be considered for more precise dose evaluation. The primary aim of the present study was to numerically demonstrate the distribution as well as the degree of diffusion of radon in the skin, with a focus on its surface layer (i.e., stratum corneum). We developed a biokinetic model that included diffusion theory at the stratum corneum, and measured radon solubility in that tissue layer as a crucial parameter. The implementation of the model suggested that the diffusion coefficient in the stratum corneum was as low as general radon-proof sheets. After a 20-min immersion in water, the simulated depth profile of radon in the skin showed that the radon activity concentration at the top surface skin layer was approximately 103 times higher than that at the viable skin layer. The information on the position of radon as a radiation source would contribute to special dose evaluation where specific target cell layers are assumed for the skin.

The first case report of pediatric acute appendicitis caused by "Candidatus Actinobaculum timonae".

A 14-year-old boy presented to the hospital with pain in the right lower abdomen. His condition was diagnosed as acute appendicitis. An emergency operation was performed, and histopathological examination revealed an actinomycete-related organism in the excised appendicitis specimen. On 16S rRNA gene sequence analysis, "Candidatus Actinobaculum timonae" was identified, which is the first known case in a pediatric patient.

[Subacute cognitive impairment and urinary retention due to primary central nervous system post-transplant lymphoproliferative disorder: a case report].

We report a 66-year-old man with primary central nervous system post-transplant lymphoproliferative disorder (PCNS-PTLD). He had received a living-donor kidney transplantation at the age of 64 years. Although he had a good postoperative course by continuing to take oral immunosuppressive agents, he was admitted to our hospital for subacute cognitive impairment and urinary retention two years after the transplantation. Brain MRI revealed high-intensity lesions on FLAIR and T2-weighted images in the left parietal operculum, deep white matter around the anterior horn of the lateral ventricle, and the genu and splenium of the corpus callosum. A part of these lesions showed ring enhancement. The cerebrospinal fluid examination revealed lymphocytic pleocytosis, elevation of protein level, and mild hypoglycorrhachia. Blood tests showed no abnormalities except for positive serum VCA-IgG antibody of Epstein-Barr virus. A brain biopsy was performed and diagnosis of PCNS-PTLD was made. There was no evidence of systemic PTLD. We reduced the dose of immunosuppressive agents and started the initial treatment with methylprednisolone pulse therapy. The patient showed a partial response to the treatment and transferred to another hospital for subsequent chemotherapy. PTLD is an important post-transplant complication that can affect the patient's prognosis. The incidence of PTLD is increasing with the growing numbers of transplantations and older age of donors and recipients. Although CNS involvement is known to be rare, PCNS-PTLD is an important differential diagnosis when symptoms of CNS origin develop in post-transplant patients.

Periosteal Myxoid Leiomyosarcoma Histologically Mimicking Extraskeletal Myxoid Chondrosarcoma: Report of a Case with Histopathological and Cytopathological Comparison with Extraskeletal Myxoid Chondrosarcoma.

Myxoid leiomyosarcoma (MLS) is a rare variant of leiomyosarcoma, with most cases occurring in the uterus. A case of MLS arising in the periosteal region of the tibia, mimicking extraskeletal myxoid chondrosarcoma (EMC), is described. The evaluation included histological and cytological comparison with EMC. The patient was a 77-year-old man with a palpable mass at the anterior aspect of the right lower leg. After diagnosis by cytopathology and biopsy examination, a wide resection was performed. The resulting cytological smears were composed primarily of spindle-shaped tumor cells in a myxoid and hemorrhagic background. Histologically, the tumor showed abundant myxoid matrix and tumor cells proliferating in a cord-like to reticular pattern, exhibiting a lace-like arrangement that mimicked EMC. Although immunohistochemical findings suggested leiomyosarcoma, a diagnosis of EMC eventually was excluded by the lack of a split signal when assessed for a rearrangement of NR4A3 by chromogenic in situ hybridization. Despite histological similarity to EMC, characteristic cytological findings of EMC such as epithelioid structures with a cord-like pattern and chondroblast-like lacunar structures were not observed in the smears of this patient's MLS. We propose that cytopathological examination of bone and soft tissue lesions is useful as a diagnostic tool in similar cases. A total diagnostic workup, including clinical, radiographic, cytopathological, histopathological, and molecular findings, is needed to ensure an accurate final diagnosis and to reduce diagnostic error.

An analysis of the immunological tumor microenvironment of primary tumors and regional lymph nodes in squamous cell lung cancer.

BACKGROUND: Various immune cells that play a central role in antitumor immunity accumulate in primary tumors and regional lymph nodes. Such cellular accumulation and the molecular expression were analyzed to elucidate the immunological tumor microenvironment. METHODS: Fifty squamous cell lung cancer patients with complete resection were included. Resected specimens from primary lung tumors and regional lymph nodes were immunostained for immune-related molecules, such as CD8, CD103, major histocompatibility complex (MHC) class I, and programmed cell death protein ligand-1 (PD-L1), and the relationship between the prognosis and clinicopathological factors was retrospectively analyzed. RESULTS: Tumor-infiltrating lymphocytes and CD8+ lymphocytes, intratumoral and intrastromal CD103+ lymphocytes, tumor diameter, pathological T and N factors, and pathological stage were significant prognostic factors for the disease-specific survival (DSS) in a univariate analysis. In a multivariate analysis, intratumoral and intrastromal CD103+ lymphocytes and pathological T and N factors were independent prognostic factors of the DSS. Significant concordance was found between the PD-L1 expression of primary tumors and metastatic lymph nodes as well as among tumor-infiltrating lymphocytes, CD8+ lymphocytes and CD103+ lymphocytes. Infiltration of CD103+ lymphocytes into the tumor was significantly correlated with an increased PD-L1 expression of cancer cells in both primary tumors and reginal lymph node metastases. Both the intratumoral infiltration of CD103+ lymphocytes and PD-L1 expression of cancer cells were significantly higher in lymph node metastases than in primary tumors. CONCLUSIONS: CD103+ lymphocyte infiltration in the primary tumor was shown to be strongly involved in the prognosis.

Cytological features of BCOR-CCNB3 sarcoma: Comparison with Ewing sarcoma and synovial sarcoma.

INTRODUCTION: BCOR-CCNB3 sarcoma (BCS) is one of the histological types classified as an undifferentiated small round cell sarcoma of bone and soft tissue. This sarcoma frequently develops in males under 20 years of age. Histologically, a delicate capillary network has been reported as a conspicuous finding. In this study, the cytological findings of BCS were observed in two cases of primary lesions and one case of a lung metastatic lesion. The cytological findings of BCS were compared with its histological mimics, and the characteristic findings of BCS were examined. METHODS: Three cases of BCS were studied, and a cytological comparison was performed with 8 cases of Ewing sarcoma (ES) and 10 cases of synovial sarcoma (SS; monophasic type: 7 cases, biphasic type: 2 cases, poorly differentiated: 1 case). RESULTS: In all BCS cases, small clusters with thin and delicate vascular cores and tiny vascular fragments were conspicuous. In ES and SS cases, although small clusters with vascular cores were observed, the vascular cores were thicker than in BCS, and no tiny vascular fragments appeared in most cases. Cytomorphological differences of tumour cells were also observed among BCS, ES, and SS. Predominantly rounded nuclei with fine chromatin and inconspicuous nucleoli can be cytological clues for BCS. CONCLUSIONS: BCS shows characteristic cytological findings that make the diagnosis of BCS more likely than that of ES and SS. Cytological evaluation is a useful tool for appropriate differential diagnosis that leads to a more accurate final diagnosis and rapid treatment.

Skeletal EWSR1-NFATC2 sarcoma previously diagnosed as Ewing-like adamantinoma: A case report and literature review emphasizing its unique radiological features.

Ewing-like adamantinoma (EAD) is a rare bone tumor. It remains unclear whether EAD belongs to adamantinoma, Ewing sarcoma (ES), or an independent category. Herein, we present a case of femoral sarcoma previously diagnosed as EAD in a 26-year-old woman. We observed amplified EWSR1 and NFATC2 fusion signals using fluorescence in situ hybridization. Prompted by its unique radiological features, we reviewed the current literature on skeletal EWSR1-NFATC2 sarcoma (ENS) and EAD. In addition to the similar histological features, we found that both ENS and EAD displayed similar characteristic radiological features, such as the tendency to occur in the diaphysis of long bones, cortical expansion and buttressing-type thickening, and bone surface involvement with saucer-like erosion without cortical destruction. We believe that these unique radiological features were related to its indolent behavior. Altogether, it is possible that previously reported EAD cases may be neither ES nor the classic adamantinoma but ENS. Further studies are needed to clarify the relationship between EAD and ENS.

Pretreatment neutrophil-to-lymphocyte ratio predicts treatment efficacy and prognosis of cytotoxic anticancer drugs, molecular targeted drugs, and immune checkpoint inhibitors in patients with advanced non-small cell lung cancer.

BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) has recently attracted attention as a prognostic predictor in patients with non-small cell lung cancer (NSCLC) who receive immune checkpoint inhibitors (ICIs). However, the utility of NLR in relation to cytotoxic anticancer drugs or molecular targeted drugs remains unclear. We determined if NLR could predict the treatment efficacy and prognosis in NSCLC patients who receive cytotoxic anticancer drugs or molecular targeted drugs, as well as ICIs, in a cross-sectional manner. METHODS: Of 658 patients with advanced NSCLC who received first-line systemic treatment in our hospital between 2008 and 2019, 312 who met the analytical criteria were included in the study. We retrospectively analyzed the ability of NLR with a cut-off value of 5 to predict time to treatment failure (TTF) and overall survival (OS) in patients who received the following treatments: first-line treatment with molecular targeted drugs (mt group, n=100); first-line treatment with cytotoxic anticancer drugs (wt group, n=212); and first-line treatment with cytotoxic anticancer drugs followed by ICIs (ICI group, n=58). RESULTS: In the high- and low-NLR mt subgroups, median TTFs were 6.7 and 14.9 months (P<0.01), respectively, and median survival times (MSTs) were 17.8 and 39.1 months (P<0.01), respectively. In the high- and low-NLR wt subgroups, median TTFs were 1.5 and 5.8 months (P<0.01), and MSTs were 6.3 and 20.7 months (P<0.01), respectively. In the high- and low-NLR ICI subgroups, median TTFs were 1.3 and 6.8 months (P<0.01), and MSTs were 9.2 and 25.8 months (P<0.01), respectively. Multivariate analysis identified NLR as a significant independent predictor of TTF [hazard ratio (HR) 1.89, P=0.01; HR 2.51, P<0.01; and HR 5.06, P<0.01 in the mt, wt, and ICI groups, respectively) and OS (HR 3.81, P<0.01; HR 2.59, P<0.01; and HR 2.48, P<0.01, respectively). CONCLUSIONS: This study showed that NLR might be a predictor of treatment efficacy and prognosis in advanced NSCLC patients who receive various systemic treatments. This finding of consistent applicability of NLR to a wide variety of systemic treatments is of great significance.

Concurrent epithelioid hemangioma and diffuse cavernous hemangioma in the rectum clinically mimicking a malignant tumor: a case report.

Epithelioid hemangioma is a rare benign vascular tumor that consists of capillary-sized vessels lined by epithelioid endothelial cells. Diffuse cavernous hemangioma is a congenital benign vascular neoplasm consisting of increased dilated vessels. We report a case of epithelioid hemangioma and diffuse cavernous hemangioma that co-occurred in the rectum. To our knowledge, this is the first report in which two rare vascular lesions coexisted. Because both epithelioid hemangioma and diffuse cavernous hemangioma are often clinically confounded by malignant tumors, differentiating these benign lesions from other possible malignant tumors is significant.

Portal hypertension in prolonged anorexia nervosa with laxative abuse: a case report with liver and kidney biopsy data.

PURPOSE: We previously reported three cases of portal hypertension in patients with prolonged anorexia nervosa (AN) with laxative abuse and self-induced vomiting; we now report a fourth, similar case. METHODS: A 34-year-old woman with anorexia nervosa, binge-eating/purging type (AN-BP), presented to the Kohnodai Hospital National Center for Global Health and Medicine Psychosomatic Medicine Department for treatment of low body weight. We conducted hepatic and renal biopsies and cardiac magnetic resonance imaging (CMR) to evaluate her complicated liver disease, renal failure, and cardiac insufficiency, respectively. RESULTS: Enhanced computed tomography revealed ascites, splenomegaly, and gastroesophageal varices, indicating portal hypertension. The liver and kidney biopsies demonstrated chronic hepatitis without evidence of hepatic cirrhosis and tubulointerstitial nephritis, respectively. CMR demonstrated decreased myocardial mass. CONCLUSION: We found tubulointerstitial nephritis and decreased myocardial mass in a patient with non-cirrhotic portal hypertension and prolonged AN with laxative abuse and habitual self-induced vomiting. We propose that reciprocal interactions between multiple factors related to AN, including laxative toxicity, dehydration, renal disorder, and cardiac insufficiency, result in portal hypertension. Level of Evidence Level V.

Relationship between Kita-Kyushu Lung Cancer antigen-1 expression and prognosis of cases with lung squamous cell carcinoma.

BACKGROUND: Previously, we identified the highly immunogenic cancer testicular antigen named Kita-Kyushu Lung Cancer antigen-1 (KK-LC-1). In this study, we analyzed the effect of KK-LC-1 expression on the prognosis of patients with resected squamous cell lung cancer. METHODS: Fifty squamous cell lung cancer patients, who received complete resection, were enrolled in this study. The expressions of KK-LC-1, CD8, human leukocyte antigen (HLA) class I, and programmed cell death protein ligand-1 (PD-L1) were assessed via immunohistochemistry staining using the specimens obtained from the participants. The association between the expression of the abovementioned molecules and patient prognosis was investigated. RESULTS: KK-LC-1 expression was observed in 21 of 50 recruited cases (42%). However, no significant correlation was found between KK-LC-1 expression and patient prognosis. The prognosis was significantly better in lung cancer cases with KK-LC-1 expression in which CD8+ T cells infiltrated the tumor. Regardless of the HLA class I expression or the PD-L1 expression, the KK-LC-1 expression in squamous cell lung cancer could not be detected as a significant prognostic factor. Furthermore, considering the polarity of the cancer tissue as epithelium, staining of KK-LC-1 tended to be strong in the area corresponding to the basal side of the tumor tissue. The Ki-67 expression was frequently observed in cancer cells on the basal side, which was consistent with the KK-LC-1 expression in representative four cases with KK-LC-1-positive squamous cell lung cancer. CONCLUSIONS: Our results indicated that lung squamous cell cancer patients with KK-LC-1 expression and the tumor infiltrating CD8+ T cells might exhibit better prognosis. KK-LC-1 might be highly expressed in cancer cells with high proliferative capacity. Larger cohort analysis is still required for further elucidation and validation of the results of this study.

Reactive astrocytes express Aggregatin (FAM222A) in the brains of Alzheimer's disease and Nasu-Hakola disease.

By combining genomic data and brain imaging data, a recent study has identified a novel gene named FAM222A that participates in the formation of amyloid-ß (Aß) plaques and brain atrophy in Alzheimer's disease (AD). FAM222A encodes a 47-kDa protein designated Aggregatin that accumulates in the center of amyloid plaques and physically interacts with Aß to facilitate Aß aggregation. Aggregatin is expressed predominantly in the central nervous system (CNS) and its levels are increased in brains of the patients with AD and in mouse models of AD. However, at present, the precise cell types that express Aggregatin in the human CNS remain unknown. By immunohistochemistry, we studied Aggregatin expression in the frontal lobe of the patients with AD, Nasu-Hakola disease (NHD), and the subjects who died of non-neurological causes (NNC). We identified the clusters of Aggregatin-positive reactive astrocytes distributed widely in the cerebral cortex of most cases examined. In contrast, small numbers of cortical neurons showed variable immunoreactivities for Aggregatin, whereas microglia and oligodendrocytes did not express Aggregatin. Importantly, amyloid plaques were not clearly labelled with anti-Aggregatin antibody. These results suggest that Aggregatin plays a primarily role in generation of reactive astrocytes in the human CNS.

Comparison of antioxidative effects between radon and thoron inhalation in mouse organs.

Radon therapy has been traditionally performed globally for oxidative stress-related diseases. Many researchers have studied the beneficial effects of radon exposure in living organisms. However, the effects of thoron, a radioisotope of radon, have not been fully examined. In this study, we aimed to compare the biological effects of radon and thoron inhalation on mouse organs with a focus on oxidative stress. Male BALB/c mice were randomly divided into 15 groups: sham inhalation, radon inhalation at a dose of 500 Bq/m3 or 2000 Bq/m3, and thoron inhalation at a dose of 500 Bq/m3 or 2000 Bq/m3 were carried out. Immediately after inhalation, mouse tissues were excised for biochemical assays. The results showed a significant increase in superoxide dismutase and total glutathione, and a significant decrease in lipid peroxide following thoron inhalation under several conditions. Additionally, similar effects were observed for different doses and inhalation times between radon and thoron. Our results suggest that thoron inhalation also exerts antioxidative effects against oxidative stress in organs. However, the inhalation conditions should be carefully analyzed because of the differences in physical characteristics between radon and thoron.