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Background 2‐deoxy‐2‐[fluorine‐18] fluoro‐d‐glucose (18F‐FDG) positron emission tomography (18F‐FDG‐PET) is a convenient modality to assess the metabolic activity within tumor cells. However, there is no consensus regarding the relationship between 18F‐FDG uptake and the immune environment in thymic epithelial tumors (TETs). We conducted a clinicopathological study to elucidate the relationship between 18F‐FDG uptake and programmed death ligands 1 and 2 (PD‐L1/PD‐L2) expression in patients with TETs. Methods: A total of 108 patients with histologically confirmed TETs classified as thymomas or thymic carcinomas who underwent surgical resection or biopsy or needle biopsy and 18F‐FDG PET before any treatment between August 2007 and March 2020 were enrolled in this study. Tumor specimens underwent immunohistochemical staining for PD‐L1, PD‐L2, GLUT1, HIF‐1α, VEGFR2, VEGF‐C, and β2 adrenergic receptor. Results: High uptakes of SUVmax, SUVmean, MTV, and TLG were identified in 28 (25.9%), 61 (56.5%), 55 (50.9%), and 55 (50.9%) of 108 patients, respectively. High uptake of SUVmax significantly correlated with PS (performance status) of 1–2, thymic carcinoma, and advanced stage, and SUVmax on 18F‐FDG uptake displayed a close association with PD‐L1 and PD‐L2 expressions, but not with MTV and TLG. Our analysis revealed that SUVmax was identified as being significant relationship for positive PD‐L1/PD‐L2 expression. GLUT1, HIF‐1α, and VEGFR2 were significantly associated with the expression of PD‐L1/PD‐L2 from the biological viewpoint. Conclusion 18F‐FDG accumulation was closely associated with the expression of PD‐L1/PD‐L2, which, in turn, was correlated with glucose metabolism and hypoxia. PD‐L1/PD‐L2 could affect the glucose metabolism and hypoxia in thymic tumor cells., High expression of PD‐L1/PD‐L2 was closely associated with high accumulation of 18F‐FDG. Angiogenetic markers were linked to the expression of PD‐L1/PD‐L2. PD‐L1 and PD‐L2 exhibited a close relationship with upregulation of tumor glucose metabolism and hypoxia.

Chyle leaks are attributed to damage to the thoracic duct itself or its tributaries during surgery. Chylothorax after lung cancer surgery can occur due to damaged thoracic duct tributaries; however, little is known of the mechanism involved. A 71‐year‐old female underwent a left upper lobectomy with hilar and mediastinal lymphadenectomy for a 1.8‐cm primary squamous cell carcinoma, and developed a chylothorax a day later. Catheter lymphangiography revealed high‐flow chyle leaks from a damaged thoracic duct tributary, known as a bronchomediastinal lymph trunk, due to a lymphatic reflex from the thoracic duct. Subsequently, catheter embolization of the tributary repaired the chylothorax. The potential for persistent chylothorax after lung cancer surgery and successful lymphatic intervention should be noted., Chylothorax after lung cancer surgery can be associated with lymphatic reflux into the damaged tributary from the thoracic duct. Catheter lymphangiography proved useful in detecting the location and direction of flow of lymphatic leakages as well as that in subsequent embolization.

Lung cancers associated with cystic airspaces have a life‐threatening risk of a missed or delayed diagnosis. Here, we report a case of pulmonary high‐grade fetal adenocarcinoma, a rare lung carcinoma associated with cystic airspaces, as confirmed by computed tomography (CT) scan. A 73‐year‐old asymptomatic male with a 52‐pack a year smoking habit was referred to our hospital. Lung CT showed a thin‐walled cystic space with exophytic and endophytic solid nodules along the cyst wall. After surgery, histological analysis of a resected lung specimen revealed a pure high‐grade fetal adenocarcinoma probably associated with emphysematous bullae in pulmonary emphysema, suggesting smoking contributed to this pure form, as well as the emphysema. In conclusion, when treating elderly men with a smoking history, physicians need to carefully examine the walls of cystic airspaces on CT for fetal adenocarcinoma. Key points Significant findings of the study • Pulmonary high‐grade fetal adenocarcinoma may be associated with emphysematous bullae manifesting as cystic air spaces as shown by computed tomography. What this study adds • When scanning by computed tomography, physicians should carefully examine the pulmonary cystic airspace walls in elderly men with a smoking history.

The lung is the organ most commonly affected by primary synovial sarcoma. Intratumoral calcification is less common in this organ versus soft tissue. Meanwhile, the presence of calcification in a lung nodule reduces the risk of lung cancer. Here, we report a case of pulmonary synovial sarcoma which manifested as a nodule with calcification, depicted on computed tomography (CT). A 52‐year‐old asymptomatic male was referred to Saitama Medical University International Medical Center and CT revealed a well‐defined nodule (1.8 cm), with punctate and eccentric calcification in the right lower lobe. Enhanced CT and 18F‐fluorodeoxyglucose positron‐emission tomography suggested a malignant tumor, and surgery was performed. Histology provided a preliminary diagnosis of monophasic spindle‐cell synovial sarcoma with hyalinized collagen bands and calcifications. Genetically, the presence of the SYT‐SSX2 fusion gene was consistent with the features of this disease. We conclude that primary pulmonary synovial sarcoma should be listed as a differential diagnosis for solitary pulmonary nodules with calcification.

Background2-Deoxy-2-[fluorine-18]-fluoro-d-glucose (18F-FDG) positron emission tomography (18F-FDG-PET) is a convenient modality to assess metabolic activity within tumor cells. However, there is no consensus regarding the relationship between 18F-FDG uptake and the immune environment in thymic epithelial tumors (TETs). We conducted a clinicopathological study to elucidate the relationship between 18F-FDG uptake and programmed death ligands 1 and 2 (PD-L1/PD-L2) expression in patients with TETs. MethodsA total of 108 patients with histologically confirmed TETs classified as thymomas or thymic carcinomas who underwent surgical resection or biopsy or needle biopsy and 18F-FDG PET before any treatment between August 2007 and March 2020 were enrolled in this study. Tumor specimens underwent immunohistochemical staining for PD-L1, PD-L2, GLUT1, HIF-1α, VEGFR2, VEGF-C and β2 adrenergic receptor. ResultsHigh uptakes of SUVmax, SUVmean, MTV and TLG were identified in 28 (25.9%), 61 (56.5%), 55 (50.9%) and 55 (50.9%) of 108 patients, respectively. High uptake of SUVmax significantly correlated with PS of 1-2, thymic carcinoma and advanced stage, and SUVmax on 18F-FDG uptake displayed a close association with PD-L1 and PD-L2 expression, but not MTV and TLG. Multivariate analysis revealed that SUVmax was identified as an independent predictor for positive PD-L1 /PD-L2 expression. GLUT1 was clarified as a significant marker for the expression of PD-L1/PD-L2 from the biological viewpoint. Conclusion18F-FDG accumulation was closely associated with the expression of PD-L1/PD-L2, which, in turn, was correlated with glucose metabolism and hypoxia. PD-L1/PD-L2 could affect glucose metabolism and hypoxia in thymic tumor cells.

Pulmonary lobectomy is the standard surgical procedure for resectable non-small cell lung cancer (NSCLC), while sublobar resection is an important surgical alternative for high-risk patients with comorbidities. We evaluated the treatment outcome and prognostic factors of sublobar resection in high-risk patients with NSCLC.Eighty three high-risk patients who underwent compromised sublobar resection for clinical-N0 NSCLC with a solid appearance were retrospectively reviewed. A total of 47 wedge resections and 36 segmentectomies performed.Poor pulmonary function and synchronous or metachronous multiple lung cancer were found in 56.7% and 20.5% of patients respectively, all requiring sublobar resection. There were 21 instances of tumor recurrence and 24 deaths during a mean follow-up of 1,500 days. There was no local recurrence in the segmentectomy group. The 3-year recurrence free survival (RFS) and overall survival (OS) were 72.6% and 73.8% respectively. A multivariate analysis indicated that resection type and lymphatic invasion were independent prognostic factors for RFS. In the wedge resection group, a ratio of surgical margin to clinical tumor size greater than 1 (MT ratio≥1) was an independent prognostic factor for RFS( 87.1%,p=0.001).Segmentectomy leads to a favorable prognosis. MT ratio was independently associated with a longer RFS in the wedge resection group.

The aim of this study was to investigate distinguishing clinicopathological features, in addition to histological invasiveness, in adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) of the lung.Patients with lung adenocarcinoma who underwent surgery at our hospital between 2007 and 2014 were reviewed, focusing on computed tomography (CT) images, operative procedures and clinical outcomes, histopathology, Ki-67 immunostaining, and EGFR-mutation status. EGFR mutations were examined using a peptide nucleic acid-locked nucleic acid PCR clamp method. Group comparisons were investigated by Mann-Whitney U or Fisher's exact tests.Of 629 patients with lung adenocarcinoma who underwent surgery, 91 (14%) of 103 AIS (n = 34) or MIA (n = 69) tumors were reviewed. The ratio of male to female patients with MIA compared to AIS was significantly higher (p 0.02). Of 103 tumors, 99 (96%) were non-mucinous. By CT, 74% of AIS appeared as pure ground-glass nodules and 75% of MIAs as part-solid ground-glass nodules. Pathological tumor diameters and Ki-67 labeling index (LI) values were significantly greater for MIAs compared to AIS (p 0.001 for both). A Ki-67 LI of ≥2.8% indicated the presence of an MIA rather than an AIS. EGFR mutations were more frequently detected in MIAs (33/69, 48%) than AIS (9/34, 26%; p = 0.055). The ratio of exon 19 deletions to exon 21 missense mutations in MIAs tended to be higher than those in AIS (p = 0.06). Patients did not experience a local recurrence or metastasis after AIS and MIAs were removed by wedge resection, segmentectomy or lobectomy. Five-year recurrence-free survival rates were 100%.Despite similar surgical outcomes for AIS and MIAs, we found differences in terms of gender, tumor diameters, CT findings, Ki-67 LI and a subset of EGFR mutations, highlighting the validity of classifying the two subtypes.

Background Immune checkpoint inhibitors (ICI) improve survival in patients with advanced non-small cell lung cancer (NSCLC) and have become one of standard therapy. It was demonstrated that nivolumab therapy for resectable NSCLC patients prior to surgery resulted in major pathological responses in 40% of the patients. On the other hand, adjuvant nivolumab therapy for melanoma resulted in longer recurrence-free survivals. Thus, it is still uncertain which host immunological status is appropriate for ICI therapy, before or after surgery. In this study, we examined the peripheral blood, and tumor tissues to elucidate immunological impact of surgery in NSCLC patients. Methods The present study comprised of 20 surgically resectable early (stage I, II, or IIIA) NSCLC patients in Saitama Medical University International Medical Center. Peripheral blood samples were collected before and after surgical resection of NSCLC. PBMCs were analyzed with LSR FortessaTM. Results Interestingly, more effector memory (EM) CCR7-CD45RA- CD8+ T cells and CD62Llow CD4+ T cells were observed in early stage NSCLC patients, compared with stage IV NSCLC patients. Significant decrease of the percentages of EM CD8+ T cells (P = 0.0045) and CD62Llow CD4+ T cells (P Conclusions After surgical removal of lung cancer, EM type T cells were converted to CM type T cells. It seems that surgery may have negative influence for innate immunity. Because PD-1 blockade therapy only activates primed effector T cells, the immunological status before surgery seems more appropriate for ICI therapy. Legal entity responsible for the study Saitama Medical University International Medical Center. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

Objectives Malignant pleural effusion (MPE) has a poor prognosis. Most patients are treated with tube thoracostomy and sclerotherapy, although its success rate is around 64%. We have investigated intrapleural perfusion with hyperthermic chemotherapy (IPHC) using cisplatin in a study with a pharmacokinetic evaluation. Methods Patients with MPE, performance status of 0–1, possibility of good lung expansion and Cr 2 . Under video-assisted thoracoscopic surgery, the thoracic cavity was filled and perfused at a speed of approximately 1L/min at a temperature of 43°C for 1h. Perfusion solution and plasma samples were periodically collected, and concentrations of protein-unbound (free) platinum, which was the active derivative of cisplatin, and total platinum were determined by flameless atomic absorption spectrometry. Results Twenty patients with MPE (8 lung cancers, 7 mesotheliomas, and 5 others) were enrolled in this study. Rate of free platinum concentration relative to total platinum concentration in perfusion solution after 1hr IPHC at 43°C was 61.1±12.9%. Area under curve (AUC) of free platinum in the pleural space was calculated to be 26.3μg/mLxh, resulting in complete control of pleural effusion for 3 months after IHPC in all cases (95% confidence interval: 83–100%). While, absorption rate of total platinum from the pleural space was 33.8±17.0% (27.4±13.6mg/m 2 ), and the maximum concentration of total platinum in serum was low, 0.66±0.31μg/mL, resulting in controllable side effects; grade 1 renal toxicity: 6 patients, grade 1 emesis: 7 patients. Conclusions IPHC with cisplatin showed favorable pharmacokinetic profiles for an optional treatment to control malignant pleural effusion.

背景．末梢肺に孤立性に発生した乳頭腫は稀であり，術前診断に難渋する．今回我々はその3切除例を報告する．症例．年齢は74，72，40歳の女性で非喫煙者であった．咳嗽1例，無症状2例で，CT画像ではそれぞれ径2.0，2.2，3.0 cmの比較的境界明瞭な充実性腫瘍であった．全症例で血中SCCの軽度上昇，1症例で血中CEAの軽度上昇を認め，FDG-PETを施行した2例とも異常高値を呈した．肺悪性腫瘍を疑い，肺葉切除を行った．病理では，3腫瘍とも扁平上皮成分と腺上皮成分に被われた線維血管性間質が乳頭状に増殖していたが，細胞異型はなく，最終診断は扁平上皮腺上皮性混合型乳頭腫であった．現在術後の再発はない．本邦における報告例15例を含めて検討した．結論．末梢肺発生の孤立性乳頭腫は，画像所見や生検による肺癌との鑑別は困難だが，腫瘍の完全切除により根治できると思われる．

症例は55歳，男性．胸部CT検診で異常陰影を指摘され，縦隔腫瘍が疑われ当科紹介受診となった．画像上，大動脈弓部直上の左鎖骨下動脈分岐部背側に接して29×29×31mmの境界明瞭な結節像を認めた．造影効果は明瞭でなく，腫瘤内に隔壁を認め，嚢胞変性のある縦隔腫瘍を疑い手術を行った．胸腔鏡で胸腔内を観察すると，大動脈弓上部に縦隔腫瘍はなく，左上葉S1+2の縦隔面に肺表面より半分程突出する硬い白色腫瘤認めた．腫瘤を含めて肺部分切除を施行した．組織学的に腫瘍は気管支上皮成分と軟骨成分より成り，肺過誤腫であった．まれではあるが，腫瘍の存在部位と隣接臓器との関係において，縦隔腫瘍と術前診断される肺腫瘍がある．

頸部伸展・頸部襟状切開にて摘出できた縦隔内甲状腺腫の切除例を報告する。【症例1】75歳女性。胸部異常陰影にて紹介。気管は右側に圧排され，甲状腺左葉下極から中縦隔に進展する7 cm大の充実性腫瘤を認めた。腫瘤の下縁は大動脈弓の高さであった。頸部襟状切開にて摘出手術を行った。腫瘍と甲状腺との連続は認めなかった。腫瘍は周囲組織から容易に剥離可能で頸部からのアプローチのみで切除できた。【症例2】48歳男性。胸部異常陰影にて紹介。右上縦隔に異常陰影を認め，気管を左側に圧排。甲状腺右葉下極から中縦隔に進展する9 cm大の充実性腫瘤を認めた。腫瘤は左腕頭静脈の背側を通過して縦隔内に進展し，下縁は奇静脈の高さであった。同様に頸部襟状切開にて摘出手術を行った。鈍的剥離によって容易に頸部に脱転され，頸部からのアプローチのみで甲状腺右葉と腫瘍を切除できた。2例とも術後経過は良好であり，病理検査でどちらも腺腫様甲状腺腫と診断された。

現在普及している自然気胸に対する胸腔鏡下手術は，従来の開胸術と比較して術後再発率がやや高い．その理由の一つとして，自動縫合器使用後の縫合線近傍のブラ新生がある．我々は臓側胸膜を強化しブラ新生の抑制と破裂防止のため，ポリグリコール酸（PGA）シートと自己血による縫合線を含めた臓側胸膜被覆法を行った．2004年1月から2006年12月までに胸腔鏡下手術を行った，術後再発が集中した40歳未満の自然気胸初回手術症例100例を，被覆法有無による術後再発の比較検討の対象とした．被覆無い症例58例，PGAシートと自己血を用いた症例33例，PGAシートとフィブリン糊を用いた症例4例，PGAシートのみの症例5例中，術後再発例はすべて被覆無い症例58例中11例（18.9％）であった．自己血の使用はフィブリン糊よりも生物学的に安全で，低コストであり，またこの被覆法は気胸再発防止に有用な方法と思われる．

Prostaglandin E1 (PGE1) has several potential therapeutic effects, including cytoprotection, vasodilation, and inhibition of platelet aggregation. This study investigates the protective action of PGE1 against hepatic ischemia/reperfusion injury in vivo using a complementary DNA microarray. PGE1 or saline was continuously administered intravenously to mice in which the left lobe of the liver was made ischemic for 30 minutes and then reperfused. Livers were harvested 0, 10, and 30 minutes postreperfusion. Messenger RNA was extracted, and the samples were labeled with two different fluorescent dyes and hybridized to the RIKEN set of 18,816 full-length enriched mouse complementary DNA microarrays. Serum alanine aminotransferase and aspartate aminotransferase levels at 180 minutes postreperfusion were significantly lower in the PGE1-treated group than in the saline-treated group. The cDNA microarray analysis revealed that the genes encoding heat-shock protein (HSP) 70, glucose-regulated protein 78, HSP86, and glutathione S-transferase were upregulated at the end of the ischemic period (0 minutes postreperfusion) in the PGE1 group. Our results suggested that PGE1 induces HSPs immediately after ischemia reperfusion. HSPs might therefore play an important role in the protective effects of PGE1 against ischemia/reperfusion injury of the liver.

ObjectiveDistinction of lymph node stations is one of the most crucial topics still not entirely resolved by many lung cancer surgeons. The nodes around the junction of the hilum and mediastinum are key points at issue. We examined the spread pattern of lymph node metastases, investigated the prognosis according to the level of the involved nodes, and conclusively analyzed the border between N1 and N2 stations.MethodsWe reviewed the records of 604 consecutive patients who underwent complete resection for non-small cell lung carcinoma of the lower lobe.ResultsThere were 390 patients (64.6%) with N0 disease, 127 (21.0%) with N1, and 87 (14.4%) with N2. Whereas 11.3% of patients with right N2 disease had skip metastases limited to the subcarinal nodes, 32.6% of patients with left N2 disease had skip metastases, of which 64.2% had involvement of N2 station nodes, except the subcarinal ones. The overall 5-year survivals of patients with N0, N1, and N2 disease were 71.0%, 50.8%, and 16.7%, respectively (N0 vs N1 P = .0001, N1 vs N2, P < .0001). Although there were no significant differences in survival according to the side of the tumor among patients with N0 or N1 disease, patients with a left N2 tumor had a worse prognosis than those with a right N2 tumor (P = .0387). The overall 5-year survivals of patients with N0, intralobar N1, hilar N1, lower mediastinal N2, and upper mediastinal N2 disease were 71.0%, 60.1%, 38.8%, 24.8%, and 0%, respectively. Significant differences were observed between intralobar N1 and hilar N1 disease (P = .0489), hilar N1 and lower mediastinal N2 disease (P = .0158), and lower and upper mediastinal N2 disease (P = .0446). Also, the 5-year survivals of patients with involvement up to station 11, up to station 10, and up to station 7 were 41.4%, 37.9% and 37.7%, respectively (difference not significant).ConclusionsN1 and N2 diseases appeared as a combination of subgroups: intralobar N1 disease, hilar N1 disease, lower mediastinal N2 disease, and upper mediastinal N2 disease. Interestingly, the survivals of patients with involvement up to interlobar nodes (station 11), main bronchus nodes (station 10), and subcarinal nodes (station 7) were identical. These data constitute the basis for a larger investigation to develop a lymph node map in lung cancer.

We report a rare case of primary mucinous adenocarcinoma of the posterior mediastinum. A 36-year-old man was referred to our hospital with right flank pain. Computed tomography showed a cystic mass in the posterior mediastinum, and the tumor displaced the diaphragm downward and the inferior vena cava forward. The patient underwent extirpation of the tumor. The cut surface of the resected tumor showed a unilocular cyst filled with abundant gray gelatinous fluid. Microscopically, the tumor had a fibrous capsule lined with cuboidal and columnar malignant epithelial cells with intracellular mucin accumulation and was diagnosed as a mucinous adenocarcinoma.

We studied the expression profiles of various stages of colorectal tumors (adenoma (AD), seven samples; carcinoma (CA), 16 samples) by using cDNA microarrays and developed ADMS (algorithm for diagnosing malignant state) method, selecting 335 clones characteristic of CA state. We, then, applied ADMS to 12 additional samples (five from primary lesions with metastasis and seven metastases); all 16 CAs and 12 metastatic tumors were diagnosed correctly as cancerous states. Although three of the seven ADs were diagnosed as "cancerous," the large size of two of these tumors suggested their potential malignancy. Our strategy for selecting clones characteristic of the malignant state is widely applicable to diagnosis and for predicting the stage of progression during multistep carcinogenesis. Of the 335 clones we selected, 135 were known genes. Included in the 135 genes were tumor suppressor and growth factor-related genes and were consistent with the literature. ADMS is a reliable means for identifying genes useful for the diagnosis of cancer.

Primary tumors of the diaphragm are very rare, and we often have difficulties in preoperative diagnosis and accurate evaluation of invasion. We experienced 3 surgical cases of tumor of diaphragm:primary mucinous adenocarcinoma, metastatic gastrointestinal stromal tumor, and mesothelioma. Besides computed tomography (CT) and conventional magnetic resonance imaging(MRI), respiratory dynamic cine magnetic resonance imaging (cine MRI) was performed. Cine MRI was acquired using steady state free precession (SSFP) sequence, and about 80 consecutive images of the same slice were taken while a patient breathed deeply. In all cases, cine MRI showed lack of tumor movement along the diaphragm during respiration. During surgery, we found that tumor was originated from diaphragm and there was no adhesion to other organs. Securing a sufficient margin, we resected tumor including the diaphragm. Since the defect of diaphragm was from 4 to 5cm in short diameter, we could close the diaphragm by direct suture. Cine MRI could provide useful information concerning discrimination between diaphragmatic and para-diaphragmatic tumor.

We have systematically characterized gene expression patterns in 49 adult and embryonic mouse tissues by using cDNA microarrays with 18,816 mouse cDNAs. Cluster analysis defined sets of genes that were expressed ubiquitously or in similar groups of tissues such as digestive organs and muscle. Clustering of expression profiles was observed in embryonic brain, postnatal cerebellum, and adult olfactory bulb, reflecting similarities in neurogenesis and remodeling. Finally, clustering genes coding for known enzymes into 78 metabolic pathways revealed a surprising coordination of expression within each pathway among different tissues. On the other hand, a more detailed examination of glycolysis revealed tissue-specific differences in profiles of key regulatory enzymes. Thus, by surveying global gene expression by using microarrays with a large number of elements, we provide insights into the commonality and diversity of pathways responsible for the development and maintenance of the mammalian body plan.

We reviewed the data on 149 patients who underwent complete resection for small-sized (≤ 2 cm)peripheral non-small cell lung cancer at our institution between January 2002 and July 2010. Patients with small-sized lung cancer underwent a lobectomy in 121, segmentectomy in 13, and wedge resection in 15 cases. The overall and 5-year disease-free survivals were 89% and 82%, respectively. The 5-year disease-free survival of patients with tumors exceeding 1.5 cm was lower than that of patients with tumors 1.5 cm or smaller (p=0.01). The 5-year disease-free survival for patients without pleulal invasion was 87%, whereas it was 45% for those with pleulal invasion (p=0.004). The 5-year disease-free survival according to the serum level of carcinoembrionic antigen( CEA) were 82% for the normal group and 70% for the high group( p=0.007). Although the results were not significantly different, patients with tumors with high maximum standardized uptake value (SUV) on FDG-PET/CT showed a trend toward a lower 5-year disease-free survival rate( p=0.10). There were no recurrences in patients with ground-glass opacity (GGO) or GGO-dominant lesion including those who underwent sublober resection. Multivariate analysis showed that tumor size and pleural invasion were independent prognostic factors. Indication of sublober resection for solid-type small-sized non-small cell lung cancer (NSCLC) should be carefully determined considering tumor size, pleural involvement, serum carcinoembryonic antigen( CEA) level, and maximum SUV.

Prostaglandin E1 (PGE1) has several potential therapeutic effects, including cytoprotection, vasodilation, and inhibition of platelet aggregation. This study investigates the protective action of PGE1 against hepatic ischemia/reperfusion injury in vivo using a complementary DNA microarray. PGE1 or saline was continuously administered intravenously to mice in which the left lobe of the liver was made ischemic for 30 minutes and then reperfused. Livers were harvested 0, 10, and 30 minutes postreperfusion. Messenger RNA was extracted, and the samples were labeled with two different fluorescent dyes and hybridized to the RIKEN set of 18,816 full-length enriched mouse complementary DNA microarrays. Serum alanine aminotransferase and aspartate aminotransferase levels at 180 minutes postreperfusion were significantly lower in the PGE1-treated group than in the saline-treated group. The cDNA microarray analysis revealed that the genes encoding heat-shock protein (HSP) 70, glucose-regulated protein 78, HSP86, and glutathione S-transferase were upregulated at the end of the ischemic period (0 minutes postreperfusion) in the PGE1 group. Our results suggested that PGE1 induces HSPs immediately after ischemia reperfusion. HSPs might therefore play an important role in the protective effects of PGE1 against ischemia/reperfusion injury of the liver.

The number of known mRNA transcripts in the mouse has been greatly expanded by the RIKEN Mouse Gene Encyclopedia project. Validation of their reproducible expression in a tissue is an important contribution to the study of functional genomics. In this report, we determine the expression profile of 57,931 clones on 20 mouse tissues using cDNA microarrays. Of these 57,931 clones, 22,928 clones correspond to the FANTOM2 clone set. The set represents 20,234 transcriptional units (TUs) out of 33,409 TUs in the FANTOM2 set. We identified 7206 separate clones that satisfied stringent criteria for tissue-specific expression. Gene Ontology terms were assigned for these 7206 clones, and the proportion of `molecular function' ontology for each tissue-specific clone was examined. These data will provide insights into the function of each tissue. Tissue-specific gene expression profiles obtained using our cDNA microarrays were also compared with the data extracted from the GNF Expression Atlas based on Affymetrix microarrays. One major outcome of the RIKEN transcriptome analysis is the identification of numerous nonprotein-coding mRNAs. The expression profile was also used to obtain evidence of expression for putative noncoding RNAs. In addition, 1926 clones (70%) of 2768 clones that were categorized as “unknown EST,” and 1969 (58%) clones of 3388 clones that were categorized as “unclassifiable” were also shown to be reproducibly expressed.

Brain metastases occur in 15% to 30% of breast cancer patients, usually as a late event. The patterns of metastases to different organs are determined by the tumor cell phenotype and interactions between the tumor cells and the organ environment.We investigated the gene expression profile occurring in brain metastases from a breast cancer cell line. We used cDNA microarrays to compare patterns of gene expression between the mouse breast cancer cell line Jyg MC (A) and a subline that often metastasis to brain, (B).By Microarray analysis about 350 of 21,000 genes were significantly up-regulated in Jyg MC (B). Many candidate genes that may be associated with the establishment of brain metastasis from breast cancer were included. Interestingly, we found that the expression of astrocyte derived cytokine receptors (IL-6 receptor, TGF-beta receptor and IGF receptor) were significantly increased in Jyg MC (B) cells. These results were confirmed by RT-PCR.These results suggest that cytokines produced by glial cells in vivo may contribute, in a paracrine manner, to the development of brain metastases from breast cancer cells.

Most public-founded large-scale sequencing projects that use cDNAs are primarily using cDNA libraries which are not enriched for full-length cDNAs. Consequently, only a fraction of the resulting ESTs matches the 5' end of the original transcript. The target of the Genome Science Laboratory of RIKEN is to clone and sequence the largest number possible of full-length mouse cDNAs in two phases. The first phase is to classify the cDNAs and the second is to complete full-length sequencing and functional annotations. We have developed two original methods to construct full-length cDNAs efficiently: 'cap-trapper', which preferentially recognizes the Cap site of mRNA; and the 'trehalose-thermoactivated reverse transcriptase', which allows the reverse transcriptase reaction at higher (60°C) temperatures. We have constructed over 80 libraries from embryonic tissues of different developmental stages and adult tissues to ensure the greatest possible coverage of the expressed mRNA. More than 200,000 successful sequencing passes have been performed with the use of two tools developed in-house: a high-throughput plasmid preparation system and the RISA 384 capillary sequencer. Most of the sequences were performed from the 3' end to select individual cDNAs. We have selected more than 30,000 different cDNAs. Using these sets of RIKEN full-length cDNA, we have established gene expression microarrays containing a 20 K set of RIKEN full-length cDNA unique mouse genes (http://genome.rtc.riken.go.jp). This set has been used to profile expression patterns of various adult and embryonic tissues. Target DNAs were PCR amplified and printed on Poly-L-lysine coated glass slides. Target DNAs were blocked by excess amounts of Cot1DNA. Probes were labelled by two-colour fluorescent dye using random primer and reverse transcriptase. Normalization has been achieved using a global normalization method. We have also developed a program to filter the noise. The experiment was done twice and reproducible results were extracted and clustered. We will present a large set of data that show the spatial and temporal expression patterns of mice. These mouse full-length 20 K cDNA microarrays are widely applicable to analyse the global expression profiling of normal and diseased status of mice.