GHSR methylation-dependent expression of a variant ligand and receptor of the ghrelin system induces thymoma tumorigenesis.

Our previous study reported that the DNA methylation of growth hormone secretagogue receptor (GHSR) was significantly higher in thymoma or thymic carcinoma (TC) than in normal thymic tissue samples. Thymic epithelial tumors (TETs) with higher GHSR DNA methylation were associated with significantly worse prognosis than those with lower levels of DNA methylation. Diversified components of the ghrelin-GHSR axis may exert opposing effects in cancer progression, depending on the cancer type in question. However, the precise function of the axis remains unclear. In the present study, the mRNA expression of five key components of the ghrelin system [native ligand ghrelin, variant ligand In-1 ghrelin, native receptor GHSR1a, variant receptor GHSR1b and acylation enzyme ghrelin O-acyltransferase (GOAT)] were examined in 58 TET samples by reverse transcription-quantitative PCR, and protein expression of GHSR1a and GHSR1b was assessed in 20 TETs using immunohistochemistry. The results revealed that In-1 ghrelin, GHSR1b (variant forms) and GOAT were more strongly expressed in thymoma compared with thymic-adjacent tissue. By contrast, no significant differences were observed in the expression of ghrelin and GHSR1a (native forms) between thymoma and thymic tissue. The mRNA expression of In-1 ghrelin and GHSR1b (variant forms) was positively associated with GHSR methylation in thymoma tissue samples. However, a relationship was not found between ghrelin, GHSR1a or GOAT expression (native forms) and GHSR methylation in thymoma. Immunohistochemical analysis revealed that mRNA expression of GHSR1a and GHSR1b generally correlated with expression of the corresponding protein, and that the expression of GHSR1b was increased in advanced-stage TETs. These results indicate that the DNA methylation of GHSR is associated with a shift from native expression (ghrelin and GHSR1a) to variant expression (In-1 ghrelin and GHSR1b), which induces the tumorigenesis of thymoma, but not TC.

Rapid growing mediastinal ectopic pancreas within ruptured thymic cyst treated using video-assisted thoracic surgery.

Ectopic pancreas (EP) is typically found within other gastrointestinal organs. Its discovery in other parts of the body, especially in the mediastinum, is exceedingly rare. This paper presents a case of a 17-year-old female patient with EP in a large, rapidly growing thymic cyst. She presented to our institution with persistent chest pain. Video-assisted thoracic surgery revealed a mediastinal mass in the setting of pleural effusion. Analysis of the fluid contents of the mass and the pleural effusion demonstrated high levels of pancreatic amylase, which supported the presence of pancreatic tissue within the mass. This is the first reported case of EP in a thymic cyst with an active pancreatic exocrine function. It is also the first reported case of mediastinal EP rupture secondary to autodigestion by amylase.

GAD1 expression and its methylation as indicators of malignant behavior in thymic epithelial tumors.

Thymic epithelial tumors (TETs) comprise thymomas and thymic carcinoma (TC). TC has more aggressive features and a poorer prognosis than thymomas. Genetic and epigenetic alterations in thymomas and TC have been investigated in an attempt to identify novel target molecules for TC. In the present study, genome-wide screening was performed on aberrantly methylated CpG islands in thymomas and TC, and the glutamate decarboxylase 1 gene (GAD1) was identified as the 4th significantly hypermethylated CpG island in TC compared with thymomas. GAD1 catalyzes the production of γ-aminobutyric acid from L-glutamic acid. GAD1 expression is abundant in the brain but rare in other tissues, including the thymus. A total of 73 thymomas and 17 TC tissues were obtained from 90 patients who underwent surgery or biopsy at Tokushima University Hospital between 1990 and 2017. DNA methylation was examined by bisulfite pyrosequencing, and the mRNA and protein expression levels of GAD1 were analyzed using reverse transcription-quantitative PCR and immunohistochemistry, respectively. The DNA methylation levels of GAD1 were significantly higher in TC tissues than in the normal thymus and thymoma tissues, and GAD1 methylation exhibited high sensitivity and specificity for discriminating between TC and thymoma. The mRNA and protein expression levels of GAD1 were significantly higher in TC tissues than in thymomas. Patients with TET with high GAD1 DNA hypermethylation and high mRNA and protein expression levels had significantly shorter relapse-free survival rates than those with low levels. In conclusion, significantly more epigenetic alterations were observed in TC tissues compared with in thymomas, which may contribute to the clinical features and prognosis of patients.

Post-mortem biopsy of a patient with late exacerbation of COVID-19 pneumonia.

Pathological findings of coronavirus disease (COVID-19) have rarely been reported owing to its contagious nature. Here, we treated an 82-year-old man whose condition was diagnosed as COVID-19 pneumonia, which exacerbated approximately 25 days after the initial onset. The patient died despite receiving intensive care. Post-mortem percutaneous needle biopsy of the lungs and liver tissue was performed, including genomic analysis, immunochemical tests, and pathological studies. Histopathology of the lungs showed both exudative and organizing diffuse alveolar damage. Supposedly, the organizing phase of acute respiratory distress syndrome (ARDS) induced COVID-19. Polymerase chain reaction (PCR) test and immunostaining of biopsy specimens showed negative results for COVID-19. Post-mortem percutaneous needle biopsy was more effective in reducing the risk of contagiousness than autopsy.

Chromate exposure induces DNA hypermethylation of the mismatch repair gene MLH1 in lung cancer.

Hexavalent chromium is recognized as a human carcinogen. Our previous studies revealed that lung cancer (LC) in chromate-exposed workers (chromate LC) had molecular features of frequent microsatellite instability (MSI), repression of MLH1 level, and aberrant DNA methylation of several tumor-suppressor genes, including MLH1. In the present study, we quantitatively investigated MLH1-promoter methylation status using bisulfite pyrosequencing of paired tumorous/nontumorous tissues from chromate and nonchromate LCs to determine the effect of chromate exposure on MLH1-promoter methylation. The methylation level of MLH1 promoter was significantly higher in chromate LC tumors (P < .001) than nonchromate LC tumors and, among chromate LC, significantly higher in tumorous tissue than nontumorous tissue (P = .004). Moreover, the methylation level of MLH1 promoter in normal lung tissue tended to be higher in chromate LC than nonchromate LC (P = .062). In addition, LC with reduced levels of MLH1 showed significantly higher methylation levels of MLH1 promoter than LC exhibiting normal MLH1 levels (P = .019). Moreover, immunohistochemical analyses determined that levels of SUV39H1, an H3K9me2-related methyltransferase, were higher in chromate LC than nonchromate LC (P = .076). Furthermore, we evaluated three DNA double-strand break-repair genes (MRE11, RAD50, and DNA-PKcs) as possible targets of MSI by fragment-length polymorphism analysis, revealing the mutation frequency of RAD50 as significantly higher in chromate LC than nonchromate LC (P = .047). These results suggest that chromate exposure might induce MLH1 hypermethylation in LC as a mechanism of chromate-induced carcinogenesis.

DNA methylation of GHSR, GNG4, HOXD9 and SALL3 is a common epigenetic alteration in thymic carcinoma.

Thymic epithelial tumors comprise thymoma, thymic carcinoma and neuroendocrine tumors of the thymus. Recent studies have revealed that the incidence of somatic non­synonymous mutations is significantly higher in thymic carcinoma than in thymoma. However, limited information is currently available on epigenetic alterations in these types of cancer. In this study, we thus performed genome­wide screening of aberrantly methylated CpG islands in thymoma and thymic carcinoma using Illumina HumanMethylation450 K BeadChip. We identified 92 CpG islands significantly hypermethylated in thymic carcinoma in relation to thymoma and selected G protein subunit gamma 4 (GNG4), growth hormone secretagogue receptor (GHSR), homeobox D9 (HOXD9) and spalt like transcription factor 3 (SALL3), which are related to cancer. We examined the promoter methylation of 4 genes in 46 thymic epithelial tumors and 20 paired thymus tissues using bisulfite pyrosequencing. Promoter methylation was significantly higher in thymic carcinoma than in thymoma and revealed a high discrimination between thymic carcinoma and thymoma in all 4 genes. Promoter methylation was higher in thymic carcinoma than in the thymus. No significant differences were observed in the promoter methylation of GNG4, HOXD9, or SALL3 between thymoma and the thymus. The promoter methylation of the 4 genes was not significantly higher in advanced­stage tumors than in early­stage tumors in all thymic epithelial tumors. Among the 4 genes, relapse­free survival was significantly worse in tumors with a higher DNA methylation than in those with a lower DNA methylation in all thymic epithelial tumors. Moreover, relapse­free survival was significantly worse in thymomas with a higher DNA methylation of HOXD9 and SALL3 than in those with a lower DNA methylation. On the whole, the findings of this study indicated that the promoter methylation of cancer­related genes was significantly higher in thymic carcinoma than in thymoma and the thymus. This is a common epigenetic alteration of high diagnostic value in thymic carcinoma and may be involved in the carcinogenesis of thymic carcinoma. However, epigenetic alterations in the 3 genes, apart from GHSR, are not involved in the tumorigenesis of thymoma.

Removal of lung lavage fluid during whole-lung lavage using biphasic cuirass ventilation chest percussion in a patient with autoimmune pulmonary alveolar proteinosis.

Autoimmune pulmonary alveolar proteinosis (PAP) is a rare lung disease. Although recombinant human granulocyte macrophage colony-stimulating factor (GM-CSF) therapy has emerged as a new therapeutic modality, whole-lung lavage (WLL) with manual chest percussion has been a standard therapy in advanced cases. The application of biphasic cuirass ventilation (BCV) instead of chest percussion has rarely been reported. We describe the case of a patient with advanced PAP who recovered well in both lungs, without complication, after we performed WLL with BCV under anesthetic mechanical ventilation. Both radiographical chest findings and clinical symptoms were improved, and oxygen therapy was finally withdrawn. This case illustrates that BCV can enhance the effective removal of lavage fluid and is an alternative to manual percussion.

Haemoptysis and bronchial congestion due to pulmonary vein stenosis after maze procedure.

Pulmonary vein stenosis (PVS) is a rare disease that can cause haemoptysis. Acquired PVS is indicated as a complication associated with cardiac catheter intervention; however, the maze procedure has not been reported to induce PVS. Here, we describe the diagnosis and treatment strategy for the first case of PVS with haemoptysis due to the maze procedure. A 56-year-old man who underwent the maze procedure seven years previously was referred for repeated haemoptysis. Contrast-enhanced computed tomography (CT) revealed complete occlusion of the left superior pulmonary vein. Bronchoscopy revealed localized bronchial congestion and varices. He was diagnosed with PVS due to the maze procedure, and he underwent catheter-balloon angioplasty. After treatment, haemoptysis disappeared and bronchial congestion and varices improved. History of cardiac ablation (surgical or catheter intervention) and localized bronchial congestion findings might facilitate the accurate diagnosis of PVS with haemoptysis. Catheter-balloon angioplasty is a minimally invasive treatment for PVS.

Prognostic significance of GAD1 overexpression in patients with resected lung adenocarcinoma.

BACKGROUND AND OBJECTIVES: In a previous genome-wide screening, we identified hypermethylated CpG islands around glutamate decarboxylase 1 (GAD1) in lung adenocarcinoma (LADC). In this study, we aimed to investigate the methylation and expression status of GAD1 and its prognostic value in patients with LADC. METHODS: GAD1 methylation and mRNA expression status were analyzed using 33 tumorous and paired non-tumorous LADC samples and publicly available datasets. The prognostic value of GAD1 overexpression was investigated using publicly available datasets of mRNA levels and 162 cases of LADC by immunohistochemistry. RESULTS: The methylation and mRNA expression levels of GAD1, each having a positive correlation, were significantly higher in LADC tumors than in paired non-tumorous tissues. LADC patients with higher GAD1 mRNA expression showed significantly poorer prognosis for overall survival in publicly available datasets. Higher immunoreactivity of GAD1 was significantly associated with the pathological stage, pleural invasion, lymph vessel invasion, and poorer prognosis for cancer-specific and disease-free survival. Multivariate analysis revealed that GAD1 protein overexpression is an independent prognosticator for disease-free survival. CONCLUSIONS: GAD1 mRNA and protein expression levels were significant prognostic factors in LADC, suggesting that they might be useful biomarkers to stratify patients with worse clinical outcomes after resection.

Evaluation of the components of mediastinal cystic lesions using imaging techniques.

OBJECTIVE: To identify and differentiate patients with mediastinal cysts from those with cystic tumors requiring surgery. METHODS: A total of 36 patients with mediastinal cystic lesions were enrolled. The patients were separated into two groups based on pathological findings : those with mediastinal cysts (n=23) and those with mediastinal tumors (n=13). The cystic components were measured using imaging parameters including mean computed tomography (CT) value, apparent diffusion coefficient (ADC), T1 signal intensity ratio (T1SIratio), and T2 signal intensity ratio (T2SI-ratio), acquired from magnetic resonance imaging (MRI) ; and standardized maximum uptake value (SUVmax) from18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). Both groups were statistically compared. RESULTS: Comparative parameters between the cysts and tumors revealed the following ratios : CT value, 40.9?21.2 versus (vs) 24.8?12.9 (p = 0.019) ;SUVmax, 1.18?0.50 vs 4.32?3.52 (p = 0.003) ; ADC, 3.46?0.96 vs 2.68?0.74 (p = 0.022) ; T1SI-ratio, 1.06?0.60 vs 1.35? 0.92 (p = 0.648) ; T2SI-ratio, 5.40?1.80 vs 4.33?1.58 (p = 0.194). However, there was no correlation between FDG uptake and ADC value. CONCLUSIONS: SUVmax from18F-FDG PET/CT and ADC derived from MRI were effective in facilitating preoperative diagnosis to differentiate mediastinal cysts from tumors. However, these examinations may be complementary to one another, not dominant. J. Med. Invest. 66 : 106-111, February, 2019.

Non­invasive monitoring of cisplatin and erlotinib efficacy against lung cancer in orthotopic SCID mouse models by small animal FDG­PET/CT and CT.

We established patient­like models of lung cancer metastasis by orthotopically implanting human non­small cell lung cancer cell lines into SCID mice. We evaluated the utilities of small­animal computed tomography (CT) and positron­emission tomography­computed tomography (PET/CT) in these models to non­invasively and repeatedly monitor the anticancer effects of cisplatin and erlotinib. We orthotopically implanted three non­small cell lung cancer cell lines, A549, FT821 and PC­9, into SCID mice. These mice were then divided into three groups: Control, cis­diamminedichloroplatinum (II) (CDDP) (7­mg/kg CDDP, single administration intraperitoneally), and erlotinib (25 mg/kg erlotinib/day, oral administration 5 days/week). After treatment initiation, we repeatedly performed PET/CT and CT measurements and assessed anticancer effects based on tumor volumes and FDG uptake. A549 tumors were not affected by CDDP or erlotinib. FT821 tumors were highly responsive to CDDP. PC­9 tumors, which have an epidermal growth factor receptor mutation, were highly responsive to erlotinib. Histological results and metastatic rates correlated with the anticancer effects shown by CT. In our orthotopic SCID mouse lung cancer models, 18FDG­PET/CT and CT imaging non­invasively and repeatedly monitored the efficacies of cisplatin and erlotinib against not only implanted tumors, but also mediastinal lymph node metastases.

Aorto-pleural fistula successfully treated by one-lung ventilation and Endobronchial Watanabe Spigots.

Aorto-pleural fistula (APF) is a rare, potentially fatal condition that should be immediately treated by an endovascular or surgical approach. In this case, we treated APF using bronchial occlusion with Endobronchial Watanabe Spigots (EWSs) after one-lung ventilation. Notably, EWS is composed of silicon for endobronchial occlusion under bronchoscopy. An 88-year-old man was referred to our hospital for sudden massive hemoptysis. We maintained the airway by emergent intubation into the right main bronchus through guided bronchoscopy. Computed tomography demonstrated an aortic aneurysm at the aortic arch, penetrating the upper lobe of the left lung. On the 18th hospital day, we performed prophylactic endobronchial occlusion with EWS. The patient was extubated shortly thereafter. Endobronchial occlusion with EWS might be effective in patients with APF who exhibit generally poor conditions. Endobronchial occlusion treatment should be performed after controlling massive bleeding by one-lung ventilation.

A case of solitary paraaortic lymph node recurrence of lung squamous cell carcinoma after resection.

Solitary abdominal paraaortic lymph node recurrence after radical lung cancer surgery is very rare. Here, we report a case of a solitary abdominal paraaortic lymph node recurrence of lung squamous cell carcinoma (SCC). A 63-year-old man was diagnosed with lung SCC (cT1cN0M0 stage IA3), underwent a video-assisted right lower lobectomy (ND2a-1), and the pathological findings showed SCC (pT1cN0M0 stage IA3). The EGFR mutation and ALK translocation statuses of SCC were negative, and adjuvant therapy was not performed. Follow-up positron emission tomography - computed tomography (PET/CT) showed a solitary fluorodeoxyglucose (FDG)-concentrated region in the swollen paraaortic lymph node. A paraaortic lymph node biopsy was performed by open laparotomy, to determine the precise diagnosis and identify the genetic status. Pathological findings revealed that the paraaortic lymph node contained poorly differentiated SCC, which was thought to metastasize from the lung cancer. The genetic status of the lymph node recurrence revealed a lack of EGFR mutations, ALK translocations, and ROS1 mutations, while the tumor proportion score (TPS) of PD-L1 was 55%, and we therefore administered pembrolizumab, an immune checkpoint inhibitor. Biopsies are very important for achieving precise diagnoses and determining the genetic statuses of tumors, since molecular-targeting drugs and immune checkpoint inhibitors are available. J. Med. Invest. 65:283-285, August, 2018.

Autofluorescence for the diagnosis of visceral pleural invasion in non-small-cell lung cancer.

OBJECTIVES: This study was conducted to evaluate the accuracy of autofluorescence as a mode of diagnosis for visceral pleural invasion of non-small-cell lung cancer compared with white-light by means of clinical questions to several thoracic surgeons. METHODS: Eight independent thoracic surgeons evaluated visceral pleural invasion in 25 cases of non-small-cell lung cancer attached to the visceral pleura on lung windows of preoperative computed tomography images. At the first study meeting to evaluate the accuracy of visceral pleural invasion diagnosis using conventional white-light images, the surgeons diagnosed visceral pleural invasion based on information in preoperative computed tomography images, histological types and videos recorded with white-light mode using a thoracoscope. At the second study meeting to evaluate the accuracy of visceral pleural invasion diagnosis using autofluorescence, the same surgeons diagnosed visceral pleural invasion based on information in 2 videos recorded in white-light mode and in autofluorescence mode using the thoracoscope. RESULTS: The overall average sensitivity, specificity and accuracy of visceral pleural invasion diagnosis by white-light versus autofluorescence mode were 64.6% vs 83.3%, 53.9% vs 73.7% and 56.5% vs 76.0%, respectively. CONCLUSIONS: The sensitivity, specificity and accuracy of visceral pleural invasion diagnosis was improved through the additional use of the autofluorescence mode compared with the white-light mode alone.

Ipsilateral shoulder pain in patients following lung resection in the decubitus position.

AIMS AND OBJECTIVES: To examine the frequency, influencing factors and clinical course of shoulder pain in patients following lung resection. BACKGROUND: Thoracoscopes have been introduced in the surgical treatment of lung cancer and allow for less invasive surgery with a minimal incision. However, decubitus position-related shoulder pain on the operated side has not yet been investigated. DESIGN: A longitudinal descriptive study. METHODS: Patients who underwent lung resection in the decubitus position. Patients were interviewed 2 days before surgery and once daily for 5 days after surgery. Interview items included background data, the concomitant use of epidural anaesthesia, operative duration, the presence of preoperative shoulder stiffness (excluding shoulder pain), type of surgery and site of operation. The intensity of pain was approximately 5 on an 11-point numerical rating scale. Descriptive statistics on patient backgrounds were obtained using SPSS Statistics 22 for Windows. RESULTS: Of the 74 patients who underwent lung resection in a decubitus position, 30 (40.5%) developed shoulder pain on the operated side. The highest rating occurred 1 day after surgery and decreased over time. The following two factors were found to influence shoulder pain on the operated side: operative duration (Z = -2.63; p = .01) and the presence of preoperative shoulder stiffness (excluding shoulder pain) (χ2  = 4.16; p = .04). CONCLUSIONS: This study demonstrated that approximately 40% of patients who underwent lung resection in the decubitus position developed shoulder pain. RELEVANCE TO CLINICAL PRACTICE: The presence of postoperative shoulder pain was related to both the duration of the operation and to the presence of preoperative shoulder stiffness. Although the shoulder pain resolves within 4 days, it causes the patient additional discomfort and distress. Therefore, further research is needed on positioning for thoracotomy in order to investigate ways to reduce or eliminate this complication of lung surgery.

Frequent silencing of RASSF1A by DNA methylation in thymic neuroendocrine tumours.

OBJECTIVES: Aberrant methylation of promoter CpG islands (CGIs) of tumour suppressor genes is a common epigenetic mechanism underlying cancer pathogenesis. The methylation patterns of thymic tumours have not been studied in detail since such tumours are rare. Herein, we sought to identify genes that could serve as epigenetic targets for thymic neuroendocrine tumour (NET) therapy. MATERIALS AND METHODS: Genome-wide screening for aberrantly methylated CGIs was performed in three NET samples, seven thymic carcinoma (TC) samples, and eight type-B3 thymoma samples. The methylation status of thymic epithelial tumours (TETs) samples was validated by pyrosequencing in a larger cohort. The expression status was analysed by quantitative polymerase chain reaction (PCR) and immunohistochemistry. RESULTS: We identified a CGI on a novel gene, RASSF1A, which was strongly hypermethylated in NET, but not in thymic carcinoma or B3 thymoma. RASSF1A was identified as a candidate gene statistically and bibliographically, as it showed frequent CGI hypermethylation in NET by genome-wide screening. Pyrosequencing confirmed significant hypermethylation of a RASSF1A CGI in NET. Low-grade NET tissue was more strongly methylated than high-grade NET. Quantitative PCR and immunohistochemical staining revealed that RASSF1A mRNA and protein expression levels were negatively regulated by DNA methylation. CONCLUSIONS: RASSF1A is a tumour suppressor gene epigenetically dysregulated in NET. Aberrant methylation of RASSF1A has been reported in various tumours, but this is the first report of RASSF1A hypermethylation in TETs. RASSF1A may represent an epigenetic therapeutic target in thymic NET.

[Malignant Pleural Mesothelioma Presenting Refractory Pneumothorax Successfully Treated by Intrapleural Administration of Diluted Fibrin Glue;Report of a Case].

Malignant pleural mesothelioma sometimes accompanies intractable neumothorax due to the visceral pleural invasion of the tumor. A 68-years-old man was found to have massive pleural effusion and pleural mass combined with pneumothorax by computed tomography(CT). CT guided biopsy revealed the mass to be malignant pleural mesothelioma. Since continuous air leakage was observed by chest drainage, pleurodesis by OK-432 twice and bronchial occlusion by Endobronchial Watanabe Spigot (EWS)were performed. But air leakage continued, and the surgery was performed, however the treatment failed to stop the air leakage. Finally, the intrapleural administration of diluted fibrin glue was challenged and the air leakage stopped immediately after the treatment.

Frequent silencing of the candidate tumor suppressor TRIM58 by promoter methylation in early-stage lung adenocarcinoma.

In this study, we aimed to identify novel drivers that would be epigenetically altered through aberrant methylation in early-stage lung adenocarcinoma (LADC), regardless of the presence or absence of tobacco smoking-induced epigenetic field defects. Through genome-wide screening for aberrantly methylated CpG islands (CGIs) in 12 clinically uniform, stage-I LADC cases affecting six non-smokers and six smokers, we identified candidate tumor-suppressor genes (TSGs) inactivated by hypermethylation. Through systematic expression analyses of those candidates in panels of additional tumor samples and cell lines treated or not treated with 5-aza-deoxycitidine followed by validation analyses of cancer-specific silencing by CGI hypermethylation using a public database, we identified TRIM58 as the most prominent candidate for TSG. TRIM58 was robustly silenced by hypermethylation even in early-stage primary LADC, and the restoration of TRIM58 expression in LADC cell lines inhibited cell growth in vitro and in vivo in anchorage-dependent and -independent manners. Our findings suggest that aberrant inactivation of TRIM58 consequent to CGI hypermethylation might stimulate the early carcinogenesis of LADC regardless of smoking status; furthermore, TRIM58 methylation might be a possible early diagnostic and epigenetic therapeutic target in LADC.

Non-invasive monitoring of anticancer effects of cisplatin on lung cancer in an orthotopic SCID mouse model using [¹8F] FDG PET-CT.

Positron emission tomography-computed tomography (PET-CT) with [18F] fluorodeoxyglucose (FDG) has recently been applied for evaluating tumor response to anticancer therapy. The aim of the present study was to evaluate the utility of FDG PET-CT in monitoring non-invasively and repeatedly the inhibitory effect of cisplatin (CDDP) on an orthotopic lung cancer model. Validation of in vivo FDG uptake in human lung cancer Ma44-3 cell line in an orthotopic SCID mouse model was carried out. Next, we assessed the use of FDG PET-CT to monitor the response of orthotopic lung cancer to the anticancer effect of CDDP. SCID mice were divided into the CDDP group (7 mg/kg single dose intraperitoneally) and the control group. Tumor volume and maximal standardized uptake value (SUV max) were calculated for all mice. All mice were sacrificed for histopathologic analysis. Validation of FDG PET-CT showed that tumor volume and SUV max were significantly correlated with postmortem tumor length measured in specimens (P=0.023) and (P=0.012), respectively, and there was a significant correlation between SUV max and tumor volume (P=0.048). Response monitoring showed that significant growth inhibition by CDDP in the form of SUV max of the CDDP group was significantly lower than that of the control group on day 8 (P=0.02) and on day 13 (P=0.003). Tumor volume of the CDDP group was significantly lower than that of the control group on day 13 (P=0.03). The present study supports using FDG PET-CT in monitoring tumor progression and therapeutic response of lung cancer in an orthotopic model non­invasively and repeatedly.