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Purpose: Gefitinib is an effective first-line chemotherapy for advanced non-small cell lung cancer (NSCLC) patients harboring sensitive EGFR mutations. However, whether second-line platinum combination chemotherapy after first-line gefitinib treatment shows similar effects to first-line platinum combination chemotherapy in these patients remains unclear. Therefore, we here aimed to investigate the efficacy of platinum combination chemotherapy after first-line gefitinib treatment in NSCLC patients harboring sensitive EGFR mutations. Methods/patients: We retrospectively evaluated the clinical effects of second-line platinum combination chemotherapy after first-line gefitinib treatment in NSCLC patients harboring sensitive EGFR mutations (exon 19 deletion or exon 21 L858R mutation) at five institutions. All patients were initially treated with gefitinib (250 mg/day) followed by platinum combination chemotherapy as second-line chemotherapy. Results: Between January 2006 and December 2012, 42 patients [8 men, 34 women; median age, 63 years (range 39-75 years)] were enrolled. The overall response rate, disease control rate, and median progression-free survival (PFS) were 26.2, 61.9 %, and 5.1 months, respectively, after the second-line treatment. The corresponding values for first-line gefitinib treatment were 69.0, 95.2 %, and 11.1 months, respectively. Moreover, second-line platinum combination chemotherapy with pemetrexed or bevacizumab-containing regimens was independently associated with improved PFS. Conclusions: Second-line platinum combination chemotherapy after first-line gefitinib treatment in NSCLC patients harboring sensitive EGFR mutations was effective and showed equivalent outcomes to first-line platinum combination chemotherapy. After failure of first-line gefitinib therapy, second-line platinum combination chemotherapy with pemetrexed or bevacizumab might result in improved PFS. [ABSTRACT FROM AUTHOR]

Background The association between human papillomavirus ( HPV) and squamous cell carcinoma ( SCC) has been reported; however, the prevalence of HPV infection varies, and the clinical characteristics of HPV-positive cases remain unknown. Objectives To elucidate the frequency of HPV infection in a series of Japanese patients with SCC and to identify the characteristics of HPV-positive cases. Methods We evaluated 38 patients with SCC treated at our department. HPV typing was performed using SCC samples from different body sites. Immunohistochemical staining for HPV proteins and p16 INK4a was performed, in addition to polymerase chain reaction and in situ hybridization. The clinical characteristics of the HPV-positive cases were clarified. Results Two genital lesions were positive for HPV type 16. Both cases showed basaloid features histopathologically, and were considered to have SCC that had arisen from bowenoid papulosis. p16 INK4a expression was observed in 11 cases, including the two HPV-positive cases. Conclusions The present study indicates that the prevalence of HPV is not high and that bowenoid papulosis is an HPV-associated precancerous lesion. Further investigation is necessary to assess the relationship between HPV infection and SCC. [ABSTRACT FROM AUTHOR]

Background:Amino-acid transporters are necessary for the tumour cell growth and survival, and have a crucial role in the development and invasiveness of cancer cells. But, it remains unclear about the prognostic significance of L-type amino-acid transporter 1 (LAT1), system ASC amino-acid transporter-2 (ASCT2), and xCT expression in patients with tongue cancer. We conducted the clinicopathological study to investigate the protein expression of these amino-acid transporters in tongue cancer.Methods:Eighty-five patients with surgically resected tongue cancer were evaluated. Tumour sections were stained by immunohistochemistry for LAT1, ASCT2, xCT, 4F2hc/CD98hc (4F2hc), Ki-67, and microvessel density (MVD) determined by CD34, and p53.Results:L-type amino-acid transporter 1 and 4F2hc were highly expressed in 61% (52 out of 85) and 45% (38 out of 47), respectively. ASC amino-acid transporter-2 and xCT were positively expressed in 59% (50 out of 85) and 21% (18 out of 85), respectively. The expression of both LAT1 and ASCT2 was significantly associated with disease staging, lymph-node metastasis, lymphatic permeation, 4F2hc expression and cell proliferation (Ki-67). xCT expression indicated a significant association with advanced stage and tumour factor. By univariate analysis, disease staging, lymphatic permeation, vascular invasion, LAT1, ASCT2, 4F2hc, and Ki-67 had a significant relationship with overall survival. Multivariate analysis confirmed that LAT1 was an independent prognostic factor for predicting poor prognosis.Conclusions:L-type amino-acid transporter 1 and ASCT2 can serve as a significant prognostic factor for predicting worse outcome after surgical treatment and may have an important role in the development and aggressiveness of tongue cancer. [ABSTRACT FROM AUTHOR]

Purpose: (18)F-FAMT as an amino-acid tracer for positron emission tomography (PET) is useful for detecting human neoplasms. (18)F-FAMT is accumulated in tumour cells solely via L-type amino-acid transporter 1 (LAT1). This study was conducted to investigate the biological significance of (18)F-FAMT uptake in patients with oesophageal cancer.Methods: From April 2008 to December 2011, 42 patients with oesophageal cancer underwent both (18)F-FAMT PET/CT and (18)F-FDG PET/CT before surgical treatment. The immunohistochemical analysis of LAT1, CD98, Ki-67, CD34, p53, p-Akt and p-mTOR was performed on the primary lesions. In vitro experiments were performed to examine the mechanism of (18)F-FAMT uptake.Results: High uptake of (18)F-FAMT was significantly associated with advanced stage, lymph node metastasis and the expression of LAT1, CD98, Ki-67 and CD34. LAT1 expression yielded a statistically significant correlation with CD98 expression, cell proliferation, angiogenesis and glucose metabolism. In vitro experiments revealed that (18)F-FAMT was specifically transported by LAT1.Conclusions: The uptake of (18)F-FAMT within tumour cells is determined by the LAT1 expression and correlated with cell proliferation and angiogenesis in oesophageal cancer. The present experiments also confirmed the presence of LAT1 as an underlying mechanism of (18)F-FAMT accumulation. [ABSTRACT FROM AUTHOR]

Background:ASC amino-acid transporter 2 (ASCT2) is a major glutamine transporter that has an essential role in tumour growth and progression. Although ASCT2 is highly expressed in various cancer cells, the clinicopathological significance of its expression in non-small cell lung cancer (NSCLC) remains unclear.Methods:One hundred and four patients with surgically resected NSCLC were evaluated as one institutional cohort. Tumour sections were stained by immunohistochemistry (IHC) for ASCT2, Ki-67, phospho-mTOR (mammalian target of rapamycin), and CD34 to assess the microvessel density. Two hundred and four patients with NSCLC were also validated by IHC from an independent cohort.Results:ASC amino-acid transporter 2 was expressed in 66% of patients, and was closely correlated with disease stage, lymphatic permeation, vascular invasion, CD98, cell proliferation, angiogenesis, and mTOR phosphorylation, particularly in patients with adenocarcinoma (AC). Moreover, two independent cohorts confirmed that ASCT2 was an independent marker for poor outcome in AC patients.Conclusions:ASC amino-acid transporter 2 expression has a crucial role in the metastasis of pulmonary AC, and is a potential molecular marker for predicting poor prognosis after surgery. [ABSTRACT FROM AUTHOR]

Background:On the basis of our recent findings of oncogenic KRAS-induced interleukin-8 (IL-8) overexpression in non-small cell lung cancer, we assessed the clinicopathological and prognostic significances of IL-8 expression and its relationship to KRAS mutations in lung adenocarcinomas.Methods:IL-8 expression was examined by quantitative RT-PCR using 136 of surgical specimens from lung adenocarcinoma patients. The association between IL-8 expression, clinicopathological features, KRAS or EGFR mutation status and survival was analysed.Results:IL-8 was highly expressed in tumours from elderly patients or smokers and in tumours with pleural involvement or vascular invasion. In a non-smokers' subgroup, IL-8 level positively correlated with age. IL-8 was highly expressed in tumours with KRAS mutations compared with those with EGFR mutations or wild-type EGFR/KRAS. Lung adenocarcinoma patients with high IL-8 showed significantly shorter disease-free survival (DFS) and overall survival (OS) than those with low IL8. DFS and OS were significantly shorter in the patients with mutant KRAS/high IL-8 than in those with wild-type KRAS/low IL-8. Cox regression analyses demonstrated that elevated IL-8 expression correlated with unfavourable prognosis.Conclusions:Our findings suggest that IL-8 expression is associated with certain clinicopathological features including age and is a potent prognostic marker in lung adenocarcinoma, especially in oncogenic KRAS-driven adenocarcinoma. [ABSTRACT FROM AUTHOR]

Purpose:18F-FAMT as an amino-acid tracer for positron emission tomography (PET) is useful for detecting human neoplasms. 18F-FAMT is accumulated in tumour cells solely via L-type amino-acid transporter 1 (LAT1). This study was conducted to investigate the biological significance of 18F-FAMT uptake in patients with oesophageal cancer.Methods:From April 2008 to December 2011, 42 patients with oesophageal cancer underwent both 18F-FAMT PET/CT and 18F-FDG PET/CT before surgical treatment. The immunohistochemical analysis of LAT1, CD98, Ki-67, CD34, p53, p-Akt and p-mTOR was performed on the primary lesions. In vitro experiments were performed to examine the mechanism of 18F-FAMT uptake.Results:High uptake of 18F-FAMT was significantly associated with advanced stage, lymph node metastasis and the expression of LAT1, CD98, Ki-67 and CD34. LAT1 expression yielded a statistically significant correlation with CD98 expression, cell proliferation, angiogenesis and glucose metabolism. In vitro experiments revealed that 18F-FAMT was specifically transported by LAT1.Conclusions:The uptake of 18F-FAMT within tumour cells is determined by the LAT1 expression and correlated with cell proliferation and angiogenesis in oesophageal cancer. The present experiments also confirmed the presence of LAT1 as an underlying mechanism of 18F-FAMT accumulation. [ABSTRACT FROM AUTHOR]

KRAS mutations are one of the most common driver mutations in non-small-cell lung cancer (NSCLC) and finding druggable target molecules to inhibit oncogenic KRAS signaling is a significant challenge in NSCLC therapy. We recently identified epiregulin (EREG) as one of several putative transcriptional targets of oncogenic KRAS signaling in both KRAS-mutant NSCLC cells and immortalized bronchial epithelial cells expressing ectopic mutant KRAS. In the current study, we found that EREG is overexpressed in NSCLCs harboring KRAS, BRAF or EGFR mutations compared with NSCLCs with wild-type KRAS/BRAF/EGFR. Small interfering RNAs (siRNAs) targeting mutant KRAS, but not an siRNA targeting wild-type KRAS, significantly reduced EREG expression in KRAS-mutant and EREG-overexpressing NSCLC cell lines. In these cell lines, EREG expression was downregulated by MEK and ERK inhibitors. Importantly, EREG expression significantly correlated with KRAS expression or KRAS copy number in KRAS-mutant NSCLC cell lines. Further expression analysis using 89 NSCLC specimens showed that EREG was predominantly expressed in NSCLCs with pleural involvement, lymphatic permeation or vascular invasion and in KRAS-mutant adenocarcinomas. In addition, multivariate analysis revealed that EREG expression is an independent prognostic marker and EREG overexpression in combination with KRAS mutations was associated with an unfavorable prognosis for lung adenocarcinoma patients. In KRAS-mutant and EREG overexpressing NSCLC cells, siRNA-mediated EREG silencing inhibited anchorage-dependent and -independent growth and induced apoptosis. Our findings suggest that oncogenic KRAS-induced EREG overexpression contributes to an aggressive phenotype and could be a promising therapeutic target in oncogenic KRAS-driven NSCLC. [ABSTRACT FROM AUTHOR]

Objective: L-[3-(18)F]-alpha-methyltyrosine ((18)F-FAMT) is an amino-acid tracer for positron emission tomography (PET), with uptake related to overexpression of L-type amino-acid transporter 1 and proliferative activity in tumour cells. This study evaluated the diagnostic performance of (18)F-FAMT PET compared with 2-[(18)F]-fluoro-2-deoxy-D-glucose ((18)F-FDG) PET in patients with multiple myeloma (MM). Methods: Eleven patients with MM (newly diagnosed, n = 3; relapsed after treatment, n = 8) underwent whole-body (18)F-FAMT and (18)F-FDG PET within a 2-week interval. Magnetic resonance imaging (MRI) of the spine was also performed to assess patterns of bone marrow infiltration. Tracer uptake was semi-quantitatively evaluated using maximal standardized uptake value (SUV(max)). Mean SUV was also determined for normal bone marrow and the aortic arch as mediastinal background SUV to calculate lesion-to-bone marrow (L/B) and lesion-to-mediastinum (L/M) ratios, respectively. Those values were statistically compared using Student's t test. Results: In 8 patients showing focal infiltration on MRI, 34 FDG-avid bone lesions were identified, with each showing increased FAMT uptake. Mean SUV(max) and L/B ratio of FDG (3.1 ± 1.2 and 3.3 ± 1.9, respectively) were significantly higher than those of FAMT (2.0 ± 1.0 and 2.6 ± 1.1, respectively; p < 0.05 each). In contrast, the L/M ratio of FDG showed no significant difference to that of FAMT (2.2 ± 1.0 and 2.4 ± 1.2, respectively; p = 0.3). Conclusions: Clear (18)F-FAMT PET uptake was seen in most (18)F-FDG-avid lesions among patients with MM, and an equivalent semi-quantitative value was obtained using L/M ratio. Our preliminary data suggest that (18)F-FAMT PET provides a useful imaging modality for detecting active myelomatous lesions. [ABSTRACT FROM AUTHOR]

Background:The expression of L-type amino-acid transporter 1 (LAT1) is tumour-specific and has been shown to have essential roles in cell growth and survival. However, little is known regarding the clinical significance of LAT1 expression in pancreatic cancer. This study was conducted to determine the prognostic significance of LAT1 expression.Methods:A total of 97 consecutive patients with surgically resected pathological stage I-IV pancreatic ductal adenocarcinoma were retrospectively reviewed. Tumour sections were stained by immunohistochemistry for LAT1, CD98, Ki-67 and vascular endothelial growth factor (VEGF), and microvessel density was determined by CD34 and p53.Results:L-type amino-acid transporter 1 and CD98 were highly expressed in 52.6% (51/97) and 56.7% (55/97) of cases, respectively (P=0.568). The expression of LAT1 within pancreatic cancer cells was significantly associated with disease stage, tumour size, Ki-67, VEGF, CD34, p53 and CD98. L-type amino-acid transporter 1 expression was confirmed to be a significant prognostic factor for predicting poor outcome by multivariate analysis.Conclusion:L-type amino-acid transporter 1 expression is a promising pathological marker for the prediction of outcome in patients with pancreatic cancer. [ABSTRACT FROM AUTHOR]

Background: Positron emission tomography (PET) with fluorine-18-fluorodeoxyglucose ((18)F-FDG) has been studied in thymic epithelial tumors. We evaluated the usefulness of (18)F-FDG PET for monitoring after treatment in unresectable thymic epithelial tumors. Method: Twelve patients with unresectable/metastatic thymic epithelial tumors underwent PET study with (18)F-FDG before and after chemotherapy or radiotherapy. Response and survival were analyzed according to the ratio of the peak standardized uptake value (SUV) of the tumor to the mean SUV of the mediastinum (T/M ratio). Results: Partial response (PR) evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) was noted in 4 (33%) of 12 patients, and partial metabolic response (PMR) was observed in 6 (50%) of 12 patients. PR was observed in 4 of 6 patients with PMR. In 6 patients with any response, the T/M ratio at post-treatment was significantly lower than at baseline (p = 0.0017). In 6 patients with stable disease (SD), stable metabolic disease (SMD) was observed in 5 by use of (18)F-FDG PET. No statistically significant difference of (18)F-FDG uptake between at baseline and post-therapy was observed in 6 patients with SD (p = 0.4157) and SMD (p = 0.8419). Although the overall survival after treatment showed no statistically significant difference between PMR and SMD or progressive metabolic disease in the whole group of patients including thymoma, a statistically significant difference in the overall survival was observed between 5 patients with PMR and 5 patients with non-PMR (p = 0.0280). Conclusion: Our preliminary study suggests that (18)F-FDG PET is useful for monitoring response and outcome after treatment in unresectable thymic epithelial tumors. [ABSTRACT FROM AUTHOR]

Gastrointestinal (GI) metastasis from non-small-cell lung cancer (NSCLC) is relatively rare. As most patients with GI metastasis are diagnosed on the occasion of serious complications, such as ileus or perforation, the appropriate diagnosis is important. Here, we report a case of NSCLC metastatic to the small intestine diagnosed at initial staging using ¹⁸F-fluorodeoxyglucose positron emission tomography. [ABSTRACT FROM AUTHOR]

The clinical significance of L-type amino acid transporter 1 (LAT1) expression remains unclear, whereas many experimental studies have demonstrated that LAT1 is associated with the proliferation of cancer cells. The purpose of this study was to evaluate the prognostic value of LAT1 in patients with nonsmall cell lung cancer (NSCLC). A total of 321 consecutive patients with completely resected pathologic stage I-III NSCLC were retrospectively reviewed. Expression of LAT1 and proliferative activity, as determined by the Ki-67 labelling index, was also evaluated immunohistochemically and correlated with the prognosis of patients who underwent complete resection of the tumour. Expression of LAT1 was positive in 163 patients (51%) (29% of adenocaricnoma (58 of 200 patients), 91% of squamous cell carcinoma (91 of 100 patients), and 67% of large cell carcinoma (14 of 21 patients)). The 5-year survival rate of LAT1-positive patients (51.8%) was significantly worse than that of LAT1-negative patients (87.8%; P<0.001). L-type amino acid transporter 1 expression was significantly associated with lymph node metastasis and disease stage. Multivariate analysis confirmed that positive expression of LAT1 was an independent factor for predicting a poor prognosis. There was a significant correlation between LAT1 expression and Ki-67 labelling index. LAT1 expression is a promising pathological factor to predict the prognosis in patients with resectable stage I-III NSCLC. [ABSTRACT FROM AUTHOR]

Objectives: L-[3-(18)F]-alpha-methyltyrosine ((18)F-FMT) is an amino-acid tracer for positron emission tomography (PET) and is used for tumor detection because malignant tumor cells accumulate (18)F-FMT based on the increased expression of an amino-acid transporter. This study was conducted to investigate the usefulness of (18)F-FMT PET in combination with fluorine-18-fluorodeoxyglucose ((18)F-FDG) PET for the diagnosis of sarcoidosis in patients with suspected malignancy. Setting: Twenty-four sarcoidosis patients with suspected malignancy underwent (18)F-FDG and (18)F-FMT PET. The study included 17 patients with extrapulmonary manifestation mimicking malignant disease (13 patients with systemic lymphadenopathy, 3 of them with concomitant hepatosplenic processes; 3 patients with hepatosplenic processes without concomitant lymphadenopathy; and 1 patient with multiple bone lesions), 3 patients with occurrence of bilateral hilar lymphadenopathy in cancer patients, and 4 patients with multiple nodules mimicking pulmonary metastasis. Results: All patients showed increased uptake of (18)F-FDG and no increase in the accumulation of (18)F-FMT in their lymphadenopathy. Standardized uptake values (SUVs) of (18)F-FDG and (18)F-FMT were 5.01 +/- 2.15 and 0.77 +/- 0.24, respectively (mean +/- SD). All extranodal lesions such as liver, spleen, and bone were visually positive on (18)F-FDG PET and negative on (18)F-FMT PET. No neoplasm was confirmed in all patients. In a control group of patients with lung cancer, SUVs for (18)F-FDG and (18)F-FMT were 6.34 +/- 2.52 and 1.54 +/- 0.82, respectively. Conclusion: The uptake of (18)F-FDG was positive in the sarcoid lesions, and therefore (18)F-FDG PET could not differentiate sarcoidosis from malignant disease. Use of (18)F-FMT PET in combination with (18)F-FDG PET may be the effective method to distinguish sarcoidosis from malignancy. [ABSTRACT FROM AUTHOR]

There are no established treatments for patients with extramedullary plasmacytomas; decision to select surgery, radiation, or chemotherapy is made depending on the condition of the tumor. After 2 months from chemoradiotherapy, the patient complained of nasal bleeding; facial computed tomography (CT) revealed marked growth of the intranasal tumor (Fig. [Extracted from the article]

Traumatic pulmonary pneumatocele, occurring after blunt trauma, is a relatively rare event. Traumatic pneumatoceles are benign lesions resulting from blunt chest trauma that need only conservative treatment unless complications arise. A 45-year old man was involved in a vehicle collision and was transferred to our institution. Chest imaging revealed multiple pneumatoceles in bilateral lung fields. The patient was treated conservatively without surgical intervention. The pneumatocele had completely disappeared after 4 months. [ABSTRACT FROM AUTHOR]

The article presents a rare case of expectoration of bronchogenic tumour tissue by a 77-year-old man who was diagnosed with small-cell lung cancer. The patient had a paroxysm of coughing and expectorated a greyish red fragment of tissue, and was identified as small-cell carcinoma through histological examination. After the expectoration, the patient felt better and repeated chest X-ray indicated re-expansion of the right lung.

The article presents a case study of a 41-year-old woman with pretibial dominant dystrophic epidermolysis bullosa (DDEB-Pt). Topics mentioned include the screening of DDEB-Pt, the basal cells analysis, and the immunofluorescent staining. Also mentioned are the antibody analysis, the development of protein response, and the heat shock protein.

Pseudomesotheliomatous adenocarcinoma is an uncommon variant of peripheral lung cancer. This condition mimics a malignant mesothelioma in terms of its clinical presentation and its gross and microscopic appearance. An immunohistochemical investigation is important when it is difficult to determine whether diffuse carcinomatous involvement of the pleura is secondary to metastasis, lung cancer, or mesothelioma. We herein report a very rare case of concomitant pseudomesotheliomatous adenocarcinoma, gastric cancer and esophageal cancer. [ABSTRACT FROM AUTHOR]

The article presents the case study of a 50-year-old woman who suffered with hyperglycemic coma and aspiration pneumonia. She had known to had a type 2 diabetes mellitus and had other features of the metabolic syndrome including hypertension and dyslipidemia. A differential diagnosis is suspected by changes in liver enzymes and been supported by results from various imaging modalities including ultrasonography.

The article reports that pulmonary adenocarcinoma with a localized extrapulmonary growth pattern presenting as a localized pleural tumor has not previously been disabled. Primary lung cancer mimicking pleural neoplasm--"pseudomesotheliomatous carcinoma" is considered to represent a type of peripheral lung adenocarcinoma with a distinctive diffuse growth pattern. The clinical similarities between the present case and pseudomesotheliomatous carcinoma are the marked extrapulmonary growth and the presence of a small subpleural nodule. Although the pattern of recurrence also showed a localized pleural mass, surgery for metastases can improve survival.