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Small Cell Lung Carcinoma (small + cell_lung_carcinoma)

Distribution by Scientific Domains

Medical Sciences	87%
Life Sciences	12%

Distribution within Medical Sciences

Oncology & Radiotherapy	71%
Pathology	28%

Selected Abstracts

Genetic alterations in early-stage pulmonary large cell neuroendocrine carcinoma

CANCER, Issue 6 2004
Kenzo Hiroshima M.D.
Abstract BACKGROUND Small cell lung carcinoma (SCLC) and pulmonary large cell neuroendocrine carcinoma (LCNEC) are high-grade malignant neuroendocrine tumors. Histologic differentiation between SCLC and LCNEC is difficult in some cases and to the authors' knowledge, genetic alterations associated with LCNEC have not been identified. Therefore, the authors studied genetic alterations found in LCNEC and compared them with those of SCLC and classic large cell carcinoma (CLCC). METHODS Twenty-two patients with UICC TNM Stage I LCNEC, 12 patients with Stage I CLCC, and 11 patients with SCLC with limited disease were studied. All tumors were resected completely. Loss of heterozygosity (LOH) of the tumor cells was detected using fluorescent primers. Methylation status of the p16 gene and expression of the p53 protein, retinoblastoma protein, and p16 protein were evaluated immunohistochemically. RESULTS LOH at TP53 and 13q14 was observed in most patients. The prevalence of LOH at D3S1295, D3S1234, and D5S407 was significantly higher in patients with LCNEC and SCLC than in patients with CLCC. The prevalence of LOH at D5S422 was higher in patients with CLCC and in patients with SCLC than in patients with LCNEC. Expression of the p16 protein was observed more frequently in SCLC than in CLCC or LCNEC. Hypermethylation of the p16 gene was observed more frequently in LCNEC than in SCLC. Patients with allelic losses at D3S1234 and D10S1686 had poorer prognoses compared with patients without allelic losses at these sites. CONCLUSIONS Genetic alterations of LCNEC were akin to those of SCLC. However, allelic losses at 5q and abnormalities in the p16 gene may differentiate LCNEC from SCLC. Cancer 2004. © 2004 American Cancer Society. [source]

Detection of tumor specific gene expression in bone marrow and peripheral blood from patients with small cell lung carcinoma

CANCER, Issue 4 2003
Masato Shingyoji M.D.
Abstract BACKGROUND Small cell lung carcinoma (SCLC) has the propensity to grow rapidly and metastasize extensively. Detection of micro-dissemination of SCLC may have clinical relevance. For its detection, tumor-specific gene expressions were examined in peripheral blood and bone marrow aspirate from patients with SCLC. METHODS Expression of prepro-gastrin-releasing peptide (preproGRP), neuromedin B receptor (NMB-R) and gastrin-releasing peptide receptor (GRP-R) were examined by reverse transcriptase polymerase chain reaction (RT-PCR) in peripheral blood and bone marrow aspirate from 40 untreated patients with SCLC. Control samples consisted of peripheral blood samples from 5 patients with nonsmall cell lung cancer (NSCLC) and 20 healthy volunteers. RESULTS Positive rates of preproGRP, NMB-R, and GRP-R in bone marrow aspirate of patients with SCLC were 23% (9/40), 8% (3/40), and 10% (4/40), respectively. Those rates in peripheral blood were 11% (4/38), 5% (2/38), and 29% (11/38), respectively. Although GRP-R expression was detected in patients with NSCLC and in healthy volunteers, preproGRP and NMB-R expressions were not detected in patients with NSCLC and in healthy volunteers. All three gene expressions in bone marrow were more frequently observed in patients with bone marrow metastasis, accessed by biopsy, than in patients without. PreproGRP gene expression in bone marrow was also more frequent in patients with bone metastasis, accessed by bone scintigram, than in patients without, and was related to poorer survival. CONCLUSIONS Micro-dissemination of SCLC was detectable by RT-PCR of preproGRP and NMB-R, both specific for SCLC. These gene expressions in bone marrow may be related to disease extent and prognosis. Cancer 2003;97:1057,62. © 2003 American Cancer Society. DOI 10.1002/cncr.11108 [source]

Real-time RT-PCR detection of CK19, CK7 and MUC1 mRNA for diagnosis of lymph node micrometastases in non small cell lung carcinoma

INTERNATIONAL JOURNAL OF CANCER, Issue 5 2005
Pierre Saintigny
Abstract Metastatic lymph nodes (LNs) are the major prognostic factor in resected non small cell lung carcinoma (NSCLC). However, almost 50% of pN0 patients relapse, suggesting metastatic cells undetected by current staging procedures. A combination of markers [cytokeratins 19 and 7 (CK19, CK7) and mucin type 1 (MUC1) mRNAs] was therefore evaluated by real-time RT-PCR in order to detect occult cancer cells. Forty-three NSCLC tumor samples, 4 micrometastatic, 6 metastatic and 84 histologically negative mediastinal LNs from 19 patients with NSCLC were evaluated as well as blood mononuclear cells from 29 healthy volunteers and 17 benign LNs. When tested on cell lines, RT-PCR was particularly efficient for evaluation of CK19, CK7 and MUC1 mRNA expression. All tumor samples were positive for at least 1 marker and 74% of samples were positive for all 3 markers. CK7 and CK19 mRNA were not detected in benign LN and blood cells from healthy donors in contrast with MUC1 mRNA. Only CK7 and CK19 mRNA were therefore used for evaluation of mediastinal LNs: the 6 histologically metastatic and the 4 micrometastatic LNs were positive for at least one marker. Among the 84 histologically negative LNs, 6 (7%) were positive for at least one marker, potentially changing the stage of 2 out of 19 patients. In conclusion, in our feasibility study, parallel molecular detection of CK19 and CK7 mRNA can be considered a specific diagnostic tool for the assessment of microscopic lymphatic spread. Its prognostic impact remains to be evaluated in a prospective study. © 2005 Wiley-Liss, Inc. [source]

The T-box transcription factor Tbx2: Its role in development and possible implication in cancer

IUBMB LIFE, Issue 2 2010
Amaal Abrahams
Abstract Tbx2 is a member of the T-box family of transcription factors that are crucial in embryonic development. Recent studies suggest that T-box factors may also play a role in controlling cell cycle progression and in the genesis of cancer. Tbx2 has been implicated in several developmental processes such as coordinating cell fate, patterning and morphogenesis of a wide range of tissues and organs including limbs, kidneys, lungs, mammary glands, heart, and craniofacial structures. Importantly, Tbx2 is overexpressed in several cancers including melanoma, small cell lung carcinoma, breast, pancreatic, liver, and bladder cancers and can suppress senescence, a cellular process, which serves as a barrier to cancer development. This review presents a state of the art overview of the role and regulation of Tbx2 in early embryonic development and in cancer. © 2009 IUBMB IUBMB Life, 62(2): 92,102, 2010 [source]

Significant high expression of cytokeratins 7, 8, 18, 19 in pulmonary large cell neuroendocrine carcinomas, compared to small cell lung carcinomas

PATHOLOGY INTERNATIONAL, Issue 2 2010
Ryo Nagashio
The aim of the present study was to clarify protein profiling in small cell lung carcinoma (SCLC) and pulmonary large cell neuroendocrine carcinoma (LCNEC). The proteomic approach was used, and involved cell lysate from two cell lines (N231 derived from SCLC and LCN1 derived from LCNEC), with 2-D gel electrophoresis (2-DE). In the present study, 25 protein spots with greater than twofold quantitative differences between LCN1 and N231 cells on 2-DE gels were confirmed. Within the 25 identified proteins, cytokeratins (CK) 7, 8, 18 and 19 were upregulated in LCN1 cells compared with N231 cells. The expression of CK7, 8, 18, and 19 was further studied on immunohistochemistry with 81 formalin-fixed and paraffin-embedded pulmonary carcinomas, which included 27 SCLC, 30 LCNEC, 14 adenocarcinomas, and 10 squamous cell carcinomas. Although the expression of CK7, 8, 18, and 19 was observed in all histological types, the mean immunostaining scores of CK7, 8, 18, and 19 were significantly higher in LCNEC than in SCLC (P < 0.001, P < 0.001, P < 0.01 and P < 0.001, respectively). These data suggest that the biological characteristics of LCNEC and SCLC may be different and the expression of CK may serve as differential diagnostic markers. [source]

LKB1 protein expression in neuroendocrine tumors of the lung

PATHOLOGY INTERNATIONAL, Issue 2 2008
Randa Mahmoud Sobhi Amin
During a recent investigation of LKB1 gene abnormality in lung lesions, strong expression of LKB1 protein in normal neuroendocrine (NE) cells of the bronchial epithelium was found. Because LKB1 functions as a tumor suppressor gene, the question of whether alteration of LKB1 expression is related to the development of pulmonary NE tumors of various grades was investigated. LKB1 immunohistochemistry was examined in a total of 68 primary pulmonary NE tumors consisting of 30 specimens of small cell lung carcinoma (SCLC), 23 large cell neuroendocrine carcinomas (LCNEC), two atypical carcinoids, and 13 typical carcinoids. Loss or low expression (<20% immunoreactive cells) of LKB1 protein expression was more frequently observed in high-grade NE tumors (SCLC and LCNEC; 45/53, 84.9%) than in typical and atypical carcinoids (3/15; 20%). The difference in LKB1 immunoreactivity between the high-grade NE tumors and the carcinoid group was statistically significant (P < 0.0001). In conclusion, marked reduction of LKB1 expression in high-grade NE tumors of the lung suggests a possible role of LKB1 inactivation in its tumorigenesis. Although a few previous studies indicated rare genetic alterations of LKB1 in SCLC, further studies including analysis of other NE tumors and focusing on epigenetic abnormalities of LKB1 gene are warranted. [source]

Proneurotensin/neuromedin N secreted from small cell lung carcinoma cell lines as a potential tumor marker

PROTEOMICS - CLINICAL APPLICATIONS, Issue 12 2008
Shun-ichiro Ogura
Abstract Proteins secreted from specific cancer cells have a high potential for use as tumor markers. We identified secreted proteins produced by 15 different carcinoma cell lines grown in serum-free medium using MS/MS. Proneurotensin/neuromedin N (proNT/NMN) was found in conditioned medium from four of seven small cell lung carcinoma cell lines but not from eight nonsmall cell lung carcinoma cell lines. These results indicate proNT/NMN has potential as a specific tumor marker of small cell lung carcinoma. [source]

A multicenter, randomized, Phase II study of cisplatin, etoposide, and gemcitabine or cisplatin plus gemcitabine as first-line treatment in patients with poor-prognosis small cell lung carcinoma

CANCER, Issue 4 2005
Filippo De Marinis M.D.
Abstract BACKGROUND The objective of this study was to evaluate the activity and toxicity of combined cisplatin, etoposide, and gemcitabine (PEG) and combined cisplatin plus gemcitabine (PG) in previously untreated patients with extensive-stage and poor-prognosis limited-stage small-cell lung carcinoma. METHODS One hundred forty patients (70 patients in two arms) were randomized to receive either cisplatin 70 mg/m2 on Day 1, etoposide 50 mg/m2 on Days 1,3, and gemcitabine 1000 mg/m2 on Days 1 and 8 or cisplatin 70 mg/m2 on Day 1 plus gemcitabine 1250 mg/m2 on Days 1 and 8. Both regimens were recycled every 21 days. RESULTS In total, 626 cycles were delivered (303 cycles of PEG and 323 cycles of PG), with a median of 4 cycles per patient in both arms. The objective response rate was 63% (95% confidence interval [95%CI], 49,71%) for PEG and 57% (95%CI, 43,67%) for PG, with the suggestion of a higher complete response rate in the PEG arm (18.6% and 4.3%, respectively). A similar time to disease progression (6 months in the PEG arm and 7 months in the PG arm) and a similar median survival (9.5 months in the PEG arm and 10 months in the PG arm) were observed in both arms. The PEG regimen was associated with more severe hematologic toxicity in terms of neutropenia, febrile neutropenia, and a higher rate of treatment delays and dose reductions, whereas nonhematologic toxicities did not differ between the two arms. CONCLUSIONS According to the results of this Phase II randomized trial, the PEG regimen produced a higher complete response rate but more toxicity compared with the PG regimen in patients with extensive-stage or poor-prognosis, limited-stage small cell lung carcinoma. Cancer 2005. © 2005 American Cancer Society. [source]

Neurologic disorders in 432 consecutive patients with small cell lung carcinoma

CANCER, Issue 4 2004
Tatjana Seute M.D.
Abstract BACKGROUND Neurologic complications are an important cause of morbidity and possibly also mortality in patients with small cell lung carcinoma (SCLC). The current study was undertaken to prospectively investigate survival and the frequency of neurologic disorders in patients with SCLC. METHODS Between October 1980 and September 2001, 432 consecutive patients with microscopically proven SCLC were included in the current study. Patients underwent neurologic examinations on a regular basis prior to, during, and after treatment. Routine imaging of the brain (computed tomography or magnetic resonance imaging) was performed before and after systemic therapy. RESULTS A neurologic disorder was diagnosed in approximately 56% of the SCLC patients. In nearly half of the cases, the neurologic disorder already was present at the time of diagnosis. Brain metastases (BM) were diagnosed most frequently. Seventy-four patients (18%) had BM at the time of diagnosis; in 20 of these patients, the BM did not demonstrate clinical signs. Another 101 patients developed BM during follow-up. The 2-year cumulative risk of BM reached 49% for patients with limited disease (LD) and 65% for patients with extensive disease (ED). Patients with BM as the only site of disease dissemination were found to have a poorer survival compared with LD patients. The majority of the nonmetastatic disorders preceded the diagnosis of SCLC. The syndrome of inappropriate antidiuretic hormone secretion (SIADH) was diagnosed most frequently. CONCLUSIONS In this prospective study, neurologic disorders were diagnosed in greater than half of the patients with SCLC. BM were detected most frequently. Approximately 18% of the patients were found to have BM at the time of diagnosis. In approximately 33% of the cases, these BM did not cause symptoms. BM were found to have a negative effect on survival in patients with SCLC. Cancer 2004;100:801,6. © 2004 American Cancer Society. [source]

Detection of tumor specific gene expression in bone marrow and peripheral blood from patients with small cell lung carcinoma

Epidermal growth factor receptor mutation status and clinicopathological features of combined small cell carcinoma with adenocarcinoma of the lung

CANCER SCIENCE, Issue 11 2007
Tomoya Fukui
In lung cancer, somatic mutations of epidermal growth factor receptor (EGFR) are concentrated in exons 18,21, especially in adenocarcinoma (Ad), but these mutations have rarely been reported in small cell lung carcinoma (SCLC). Combined SCLC is rare, and the EGFR mutation status and its relationship to the clinicopathological features of this tumor type have not yet been elucidated. We retrospectively studied six patients with combined SCLC with Ad components among 64 consecutive patients who underwent resection of SCLC. The clinicopathological features of each patient were reviewed, especially for the distribution pattern of the Ad component and lymph node metastases. EGFR mutations were screened by high-resolution melting analysis in each case, and were confirmed by sequencing of each mutation in the microdissected SCLC or Ad components. Regarding EGFR, no specific mutation was detected in five of the six patients, whereas one female patient who had never smoked had a missense mutation. In this case, both the SCLC and Ad components shared the same mutation in exon 21 (L858R). We identified a patient with combined SCLC with Ad sharing an identical EGFR mutation in both the SCLC and Ad components. In addition to the clinicopathological characteristics of this rare histological type of lung cancer, these findings provide useful information for better understanding the biology, natural history and clinical management of SCLC. (Cancer Sci 2007; 98: 1714,1719) [source]

Correlation between morphology and human telomerase gene amplification in bronchial brushing cells for the diagnosis of lung cancer

DIAGNOSTIC CYTOPATHOLOGY, Issue 6 2010
Yi-Bo Fan M.D.
Abstract The aim of this study was to investigate the frequency of amplification of the human telomerase gene (TERC), as measured by fluorescence in situ hybridization (FISH), in routine liquid-based cytological preparations from bronchial brushing specimens, and to assess the associations between TERC amplification, cytological diagnosis, and cytological morphology, in order to obtain further insight into these associations. Bronchial brushings from 102 patients with lung carcinoma (52 squamous-cell carcinomas, 22 adenocarcinomas, 28 small cell lung carcinomas) and 40 patients with nonmalignant disease were used. Amplification of TERC was performed using a commercially available two-color FISH probe, and slides were prepared for the SurePath liquid-based Pap test (LPT) using the same samples. Amplification of TERC was significantly associated with histological diagnoses (P < 0.05). Patients with lung cancer, and especially those with nonsmall cell lung cancer, had significantly higher percentages of cells with amplification of TERC than did patients with nonmalignant disease (P < 0.05). Comparing the FISH and LPT results, there was no significant difference in diagnostic sensitivity between the two methods (P > 0.05). However the difference in diagnostic sensitivity of the two methods for squamous-cell carcinoma was significant (P < 0.01). FISH can be performed on bronchial brushing specimens to detect amplification of TERC. This test may be an adjunct to cytology screening, especially in squamous-cell carcinoma, and may provide an indication of the potential of individual lesions to progress. Diagn. Cytopathol. 2010. © 2009 Wiley-Liss, Inc. [source]