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National Cancer Institute®
Ultima Vez Modificado: 1 de febrero del 2002
UI - 11778566
AU - Cao K; Huang H; Tu M
TI - [Clinical study of prophylactic cranial irradiation for small-cell lung cancer]
SO - Zhonghua Zhong Liu Za Zhi 2000 Jul;22(4):336-8
AD - Radiotherapy Department, Cancer Center, Sun Yat-sen University of Medical Sciences, Guangzhou 510060, China.
OBJECTIVE: To study the influence of prophylactic cranial irradiation (PCI) on survival and brain metastases in patients with limited small-cell lung cancer (SCLC). METHODS: Fiftyone patients with limited SCLC under complete remission after chemoradiotherapy were randomly divided into prophylactic cranial irradiation (PCI) group (n = 26) and control group (n = 25). Patients in PCI group received irradiation at a dose of 25.2-30.6 Gy. Survival rates were analyzed and compared by life table and Long-Rank, incidence of cranial metastases by chi 2 test. RESULTS: The clinical features of patients such as age, sex, effect of treatment before PCI were similar between the two groups. The incidence of cranial metastases was 3.8% in PCI group in contrast to 28% in the control group (P < 0.05). The 1, 2, 3-year survival rate was 84.6%, 73.1%, 42.3% respectively in PCI group and 72%, 40%, 32% respectively in the control group. The differences between the two groups of petients were statistically insignificant. No serious sequela was observed in patients receiving PCI. CONCLUSION: PCI decreases the incidence of cranial metastases for patients with limited SCLC following complete response to chemoradiotherapy, but it does not improve survival.
UI - 11521802
AU - Quoix E; Breton JL; Daniel C; Jacoulet P; Debieuvre D; Paillot N;
TI - Kessler R; Moreau L; Coetmeur D; Lemarie E; Milleron B Etoposide phosphate with carboplatin in the treatment of elderly patients with small-cell lung cancer: a phase II study.
SO - Ann Oncol 2001 Jul;12(7):957-62
AD - Pulmonology Unit, University Hospital, Strasbourg, France. Elisabeth.Quoix@chru-strasbourg.fr
BACKGROUND: Although the average age of lung cancer patients is increasing, many elderly patients remain undertreated, mainly because of the fear of higher treatment toxicity in this category of patients. We conducted a study to evaluate the efficacy and tolerability of a combination therapy with carboplatin (C) and etoposide phosphate (EP) in elderly patients with Small-Cell Lung Cancer (SCLC). PATIENTS AND METHODS: Previously untreated patients older than 70 years with stage IIIB/IV SCLC received a combination of EP (100 mg/m2 D1, D2, D3) and C (D1, dose calculated according to the Calvert formula). Response rate, survival and toxicity were assessed. RESULTS: Thirty-eight patients (mean age 76 years, range 70-88 years) received a total of 162 cycles. Eighteen patients (47%) received the six scheduled cycles. Thirty patients were evaluable for efficacy (2 CR and 20 PR). The median survival was 237 days and the one-year probability of survival was 26%. The most common adverse effect was transient grade 3 or 4 neutropenia, observed during 57% of evaluable cycles, while five episodes of febrile neutropenia also occurred, with one fatal (bacteremia). It is noteworthy that no renal or liver toxicity was observed, and no mucitis was noted. Unfortunately, a relatively high proportion of patients died shortly after the start of the study. Although most deaths seemed unrelated to the treatment, the possibility of its exacerbatory effect on comorbidities, especially cardiovascular, cannot be excluded. CONCLUSION: The two-drug regimen of carboplatin and etoposide phosphate is feasible in most elderly patients with an acceptable toxicity, and the overall results suggest that patients even older than 70 years may benefit from full treatment. Therefore, consideration should be given to offering active treatment to most patients with SCLC, regardless of age but with special attention paid to comorbidities.
UI - 11720739
AU - Kaye FJ
TI - Molecular biology of lung cancer.
SO - Lung Cancer 2001 Dec;34 Suppl 2():S35-41
AD - Genetics Branch, Center for Cancer Research, National Cancer Institute-Navy Oncology and National Naval Medical Center, Naval Hospital, Building 8/Room 5105, Bethesda, MD 20889, USA. email@example.com
Lung cancer develops slowly over many years from the sequential accumulation of gene alterations in susceptible pulmonary cells. The global epidemic of tobacco addiction has accelerated the incidence of lung cancer and has now focused increased attention on this disease worldwide. This review will briefly outline some of the tumor suppressor gene pathways that are known or suspected to play an important role in the development of this deadly malignancy.
UI - 11773518
AU - Prakash P; Manfredi TG; Jackson CL; Gerber LE
TI - Beta-carotene alters the morphology of NCI-H69 small cell lung cancer cells.
SO - J Nutr 2002 Jan;132(1):121-4
AD - Department of Food Science and Nutrition, University of Rhode Island, Kingston, RI 02881, USA. firstname.lastname@example.org
The effect of beta-carotene on the morphology of NCI-H69 small cell lung cancer cells that had undergone beta-carotene-induced growth reduction (P < 0.05) was examined. The cells were grown at 1 x 10(8) cells/L and were cultured with or without 20 micromol/L beta-carotene. The qualitative electron microscopic observations revealed that beta-carotene-treated cells contained more vacuoles than control cells not treated with beta-carotene. The quantitative image analysis showed a significantly smaller (P < 0.05) value of the nuclear roundness factor for treated cells compared with control cells, indicating an irregular nuclear morphology of beta-carotene-treated cells. The major diameter of the cells and the minor diameter of the nuclei were significantly smaller (P < 0.05), and the nuclear perimeter was significantly larger (P < 0.05) in beta-carotene-treated cells. The ratio of nucleus to cytoplasm was significantly less (P < 0.05) in beta-carotene-treated cells compared with control cells, indicating a less malignant growth of the cells. These results demonstrate that the treatment of small cell lung cancer cells with beta-carotene induces morphological changes in the cells concomitant with a reduction in their proliferation. Further investigation is required to show a direct effect of beta-carotene or its intracellular polar metabolites on the morphology of these cells.
UI - 11747218
AU - Yang YJ; Steele CT; Ou XL; Snyder KP; Kohman LJ
TI - Diagnosis of high-grade pulmonary neuroendocrine carcinoma by fine-needle aspiration biopsy: nonsmall-cell or small-cell type?
SO - Diagn Cytopathol 2001 Nov;25(5):292-300
AD - Department of Pathology, Upstate Medical University, State University of New York, Syracuse, New York 13210, USA. email@example.com
A consensus optimal therapy for large-cell neuroendocrine carcinoma of the lung has not been achieved since this entity was proposed in 1991. Accumulation of clinical data and investigation, however, can be greatly impeded by erroneous cytological diagnosis, based on which treatment may be initiated. To avoid erroneous diagnoses, cytological criteria need to be defined. Twenty cases of fine-needle aspiration specimens with a diagnosis of neuroendocrine tumor by either cytology or follow-up histology were retrospectively reviewed for cytomorphologic features. Patients' clinical data were also reviewed. Three cytomorphologic patterns were identified for large-cell neuroendocrine carcinoma, i.e., nonsmall-cell-like, small-cell-like and, mixed nonsmall-cell-small-cell-like. Small-cell-like large-cell neuroendocrine carcinoma can be mistaken for small-cell carcinoma. The most important differential features between these two entities are nuclear size and perceptibility of nucleoli of tumor cells. Copyright 2001 Wiley-Liss, Inc.
UI - 11747231
AU - Chhieng DC; Ko EC; Yee HT; Shultz JJ; Dorvault CC; Eltoum IA
TI - Malignant pleural effusions due to small-cell lung carcinoma: a cytologic and immunocytochemical study.
SO - Diagn Cytopathol 2001 Dec;25(6):356-60
AD - Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama 35249-6823, USA. firstname.lastname@example.org
Patients with small-cell lung carcinoma (SCLC) rarely present with pleural effusions. Based on morphology alone, recognition of SCLC in effusion cytology may be challenging because of the resemblance of neoplastic cells to lymphocytes. Immunocytochemistry may be helpful in its diagnosis. The objective of this study was to review the morphology and evaluate the use of immunocytochemistry in diagnosing SCLC in pleural fluids. Patients with SCLC who presented with pleural effusions were identified during a 6-yr period. The cytology and medical records were reviewed. Formalin-fixed, paraffin-embedded cell blocks of fluid specimens were immunostained with neuroendocrine markers (chromogranin A and synatophysin), cytokeratin 20 (CK20), and thyroid transcription factor-1 (TTF-1). The latter is a nuclear transcription protein that is expressed in normal respiratory epithelium and also in more than 90% of SCLCs. Of the 256 patients diagnosed with SCLC during the study period, 8 (2.7%) patients (3 females and 4 males, age range from 56-85 yr) also developed pleural effusions. One patient had 2 fluid specimens during the course of their disease, giving a total of 9 specimens. Four specimens had a positive cytologic diagnosis of SCLC, and 2 were initially diagnosed as suspicious for SCLC. The remaining 3 specimens were negative for SCLS. The specimens with a positive or suspicious diagnosis showed single and aggregates of small to medium-sized single cells with a high nuclear:cytoplasmic (N:C) ratio, round to angulated nuclei, and salt-and-pepper chromatin. Nuclear molding was also noted. Five out of 6 (83%) specimens with a positive or suspicious diagnosis of SCLC were positive for both chromogranin A and TTF-1. Synaptophysin was positive in 3 of 6 (50%) positive or suspicious cases. None of the cases were positive for CK20. All cases with a negative cytologic diagnosis were negative for chromogranin A, synatophysin, CK20, and TTF-1. In conclusion, patients with SCLC rarely present with pleural effusions. The cytology of SCLC is characteristic. The use of immunocytochemistry, particularly with antibodies to chromogranin A, TTF-1, and CK 20, aids in the differential diagnosis. Copyright 2001 Wiley-Liss, Inc.
UI - 11732293
AU - Szczesny TJ; Szczesna A
TI - [Surgical treatment of limited small cell lung cancer]
SO - Pneumonol Alergol Pol 2001;69(5-6):300-10
AD - Klinika Chirurgii Instytutu Gruzlicy i Chorob Pluc w Warszawie.
UI - 11802049
AU - Kuriakose MA; Loree TR; Rubenfeld A; Anderson TM; Datta RV; Hill H;
TI - Rigual NR; Orner J; Singh A; Hicks WL Jr Simultaneously presenting head and neck and lung cancer: a diagnostic and treatment dilemma.
SO - Laryngoscope 2002 Jan;112(1):120-3
AD - Department of Head and Neck Surgery, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, U.S.A.
OBJECTIVES/HYPOTHESIS: Synchronous tumors are defined as malignancies presenting within 6 months of the index tumors. A significant subset of patients present at initial evaluation with malignant tumors of both the head and neck (head and neck squamous cell carcinoma) and the lung, which are termed simultaneous primaries. The management and treatment outcomes in this cohort of patients have not been clearly defined and are the subject of the present review. STUDY DESIGN: Retrospective chart squamous cell carcinoma of the head and neck. Forty-two patients fulfilled the criteria for synchronous head and neck and lung malignancy. Of these, 27 patients had simultaneous tumors of the head and neck and the lung. This cohort of patients (n = 27) was stratified into three treatment groups. Patients in group A (n = 10) had resectable head and neck and lung primaries treated with curative intent. Group B (n = 8) was composed of patients who could have been treated with curative intent but declined and were given only palliative therapy. Patients in group C (n = 9) were candidates for only palliative treatment. RESULTS: The estimated 5-year disease-specific survival in group A was 47%, whereas patients in group B had a 5-year disease-specific survival of only 13% (P =.05). There were no survivors beyond 1 year in group C. The presence of mediastinal adenopathy in patients in group A portended poor clinical outcome. There was an estimated 5-year disease-specific survival of 51% in patients with no preoperative evidence of mediastinal adenopathy (n = 7), whereas 67% of patients with radiological evidence of mediastinal adenopathy died (two of three patients). CONCLUSION: The presence of simultaneous head and neck squamous cell carcinoma and pulmonary malignancies should not be a deterrent to aggressive surgical therapy because a potentially satisfactory outcome can be expected in these patients.
UI - 11807782
AU - Sartorius UA; Krammer PH
TI - Upregulation of Bcl-2 is involved in the mediation of chemotherapy resistance in human small cell lung cancer cell lines.
SO - Int J Cancer 2002 Feb 10;97(5):584-92
AD - Tumor Immunology Program, Division of Immunogenetics, German Cancer Research Center, Heidelberg, Germany.
Chemotherapeutic drugs eliminate cancer cells by induction of apoptosis. Resistance to chemotherapy is partly due to a decreased apoptosis rate. Here we investigated resistance to anticancer drugs in 9 small cell lung cancer (SCLC) cell lines. Apoptosis was induced by cisplatin, doxorubicin and etoposide and was found to be independent of caspase-8 expression. Since caspase-8 is essential for signal transduction of death receptor-mediated apoptosis, all known death receptor systems are thus not required for drug-induced apoptosis in SCLC. Furthermore, we found that anticancer drugs could activate the mitochondrial pathway of apoptosis without involvement of upstream caspases. Finally, by culturing 3 sensitive cell lines in subtherapeutic concentrations of etoposide, resistant cells were generated that exhibit cross-resistance to cisplatin and doxorubicin. Drug resistance was paralleled by strong upregulation of Bcl-2, which diminished apoptosis by inhibiting the loss of the mitochondrial transmembrane potential and the release of cytochrome c. The role of bcl-2 in these processes was supported by bcl-2 transfection and antisense inhibition. These results indicate that Bcl-2 contributes to drug resistance in SCLC, a finding that has profound therapeutic implications. Copyright 2001 Wiley-Liss, Inc.
UI - 11807797
AU - Blizzard L; Dwyer T
TI - Lung cancer incidence in Australia: impact of filter-tip cigarettes with unchanged tar yields.
SO - Int J Cancer 2002 Feb 10;97(5):679-84
AD - Menzies Centre for Population Health Research, University of Tasmania, Hobart, Australia. Leigh.Blizzard@utas.edu.au
Filter-tip cigarettes became popular in Australia in the late 1950s, but "tar" yields remained high for another decade. Because of this, the effect of filters independently of tar reductions can be estimated by comparing the age-adjusted incidence of lung cancer for relevant birth cohorts of Australians. Separate analyses by histologic type may throw some light on the specific effects of filters. Age-adjusted incidence of squamous cell carcinoma (SCC), small cell lung carcinoma (SCLC) and adenocarcinoma (AC) was estimated by Poisson regression for 5-year birth cohorts of Australians using lung cancer registration data for 1982-95. To take account of changes in smoking prevalence, ever-smoker less never-smoker differences in age-adjusted incidence were estimated. Comparisons were made for smokers born during 1930-34 and 1940-44. Smokers born in 1940-44 commenced smoking at the time of introduction of filter-tips. Age-adjusted incidence of SCC (-23%) and SCLC (-21%) but not AC (+7%) was lower for female smokers born during 1940-44. For male smokers, rates of SCC (-42%), SCLC (-43%) and AC (-24%) were each lower. The high rates overall of 1940s-born women were due to disproportionately higher incidence of AC, the type that comprised 42% of diagnoses with histologic confirmation. In Australia, the switch to filter-tip cigarettes prior to any reduction in tar yields was associated with reduced incidence of SCC and SCLC, and of AC for men only. Rates of AC were not reduced for women, indicating that other factors were important for this type of lung cancer. Copyright 2001 Wiley-Liss, Inc.
UI - 11693903
AU - Argiris A; Murren JR
TI - Staging and clinical prognostic factors for small-cell lung cancer.
SO - Cancer J 2001 Sep-Oct;7(5):437-47
AD - Northwestern University Medical School and Robert H. Lurie Comprehensive Cancer Center, Chicago, Illinois 60611, USA.
The two-stage system introduced by the Veterans' Affairs Lung Study Group continues to be widely utilized in small-cell lung cancer (SCLC), mainly because of its simplicity and clinical utility. Approximately one third of patients with SCLC present with limited-stage disease, which is defined as disease that can be encompassed in a tolerable radiation field. However, this definition is controversial when it is applied to the staging classification of patients with locoregionally advanced disease manifested as the presence of an ipsilateral pleural effusion, contralateral supraclavicular lymphadenopathy, or contralateral mediastinal lymphadenopathy. The more descriptive TNM system is useful for patients with disease limited to the lung, when surgical resection may be feasible; this occurs in far less than 10% of cases. As shown by clinical studies and autopsy data, metastatic disease frequently involves the liver, adrenals, bone, bone marrow, and brain. History and physical examination, complete blood count and chemistry studies, chest x-ray studies, computed tomography of the chest or upper abdomen, computed tomographic scanning or magnetic resonance imaging of the brain, and bone scans are recommended for the pretreatment evaluation of patients with SCLC. A bone marrow biopsy may be omitted for patients with normal blood counts, normal lactate dehydrogenase level, and negative result on bone scan. The use of new imaging modalities, such as magnetic resonance imaging of the bone marrow and positron emission tomographic scanning, may optimize staging evaluation. Multiple prognostic parameters have been identified for patients with SCLC, the most important of which are the stage or extent of disease, performance status, serum lactate dehydrogenase level, and male gender. Identification of risk factors for treatment-related mortality is important for the management of patients with SCLC.
UI - 11782387
AU - Konishi H; Nakagawa T; Harano T; Mizuno K; Saito H; Masuda A; Matsuda H;
TI - Osada H; Takahashi T Identification of frequent G(2) checkpoint impairment and a homozygous deletion of 14-3-3epsilon at 17p13.3 in small cell lung cancers.
SO - Cancer Res 2002 Jan 1;62(1):271-6
AD - Division of Molecular Oncology, Aichi Cancer Center Research Institute, Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan.
Accumulating evidence suggests that a coordinately controlled G(2) checkpoint prevents cells with damaged DNA from entering mitosis, thus playing an important role in the maintenance of chromosomal integrity. In the study presented here, we identified a homozygous deletion of the 14-3-3epsilon gene, which resides within a previously identified, commonly deleted region at 17p13.3 in lung cancers, in two small cell lung cancer cell lines that originate from distinct metastatic sites of the same patients. The introduction of 14-3-3epsilon induced significantly restored G(2) checkpoint responses, which resulted in the reduction of mitotic cells as well as of aberrant mitotic figures in the X-ray-irradiated 14-3-3epsilon-null small cell lung cancer cell line. Interestingly, we also found that the G(2) checkpoint response is frequently impaired to various degrees in a large fraction of small cell lung cancer cell lines. These findings suggest the possible involvement of the perturbed G(2) checkpoint in the pathogenesis of this aggressive form of human lung cancers.
UI - 11720426
AU - Sculier JP; Paesmans M; Lecomte J; Van Cutsem O; Lafitte JJ; Berghmans
TI - T; Koumakis G; Florin MC; Thiriaux J; Michel J; Giner V; Berchier MC; Mommen P; Ninane V; Klastersky J; European Lung Cancer Working Party A three-arm phase III randomised trial assessing, in patients with extensive-disease small-cell lung cancer, accelerated chemotherapy with support of haematological growth factor or oral antibiotics.
SO - Br J Cancer 2001 Nov 16;85(10):1444-51
AD - Department of Medicine, Institut Jules Bordet, 1rue Heger-Bordet, B-1000 Bruxelles, Belgium.
The European Lung Cancer Working Party (ELCWP) designed a 3-arm phase III randomised trial to determine the role of accelerated chemotherapy in extensive-disease (ED) small-cell lung cancer (SCLC). Eligible patients were randomised between the 3 following arms: (A) Standard chemotherapy with 6 courses of EVI (epirubicin 60 mg m(-2), vindesine 3 mg m(-2), ifosfamide 5 g m(-2); all drugs given on day 1 repeated every three weeks. (B) Accelerated chemotherapy with EVI administered every 2 weeks and GM-CSF support. (C) Accelerated chemotherapy with EVI and oral antibiotics (cotrimoxazole). Primary endpoint was survival. 233 eligible patients were randomised. Chemotherapy could be significantly accelerated in arm B with increased absolute dose-intensity. Best response rates, in the population of evaluable patients, were, respectively for arm A, B and C, 59%, 76% and 70%. The response rate was significantly higher in arm B in comparison to arm A (P = 0.04). There was, however, no survival difference with respective median duration and 2-year rate of 286 days and 5% for arm A, 264 days and 6% for arm B and 264 days and 6% for arm C. Severe thrombopenia occurred more frequently in arm B but without an increased rate of bleeding. Non-severe infections were more frequent in arm B and severe infections were less frequent in arm C. Our trial failed to demonstrate, in ED-SCLC, a survival benefit of chemotherapy acceleration by using GM-CSF support.
UI - 11778234
AU - Yang J; Li R; Li A
TI - [Clinical significance of ProGRP31-98 in patients with small-cell lung cancer]
SO - Zhonghua Zhong Liu Za Zhi 2000 May;22(3):216-8
AD - Department of Medical Oncology, First Clinical Medical College, Xi'an Medical University, Xi'an 710061, China.
OBJECTIVE: To determine the clinical significance of serum level of pro-gastrin-releasing peptide 31-98 (ProGRP31-98) for small-cell lung cancer (SCLC) in comparison with neuron-specific enolase (NSE). METHODS: Serum level of ProGRP31-98 was measured by ELISa in 30 patients with SCLC, 30 patients with non-small-cell lung cancer (NSCLC), 10 patients with SCLC who had received treatment, 15 patients with benign lung diseases and 15 normal subjects. The receiver operating characteristic (ROC) curve was used to set the cut-off value and evaluate the diagnostic accuracy. RESULTS: The serum level of ProGRP31-98 was significantly increased in patients with SCLC as compared to that of the normal controls as well as that in any other groups of patients. It was higher in SCLC patients with extensive disease than in patients with limited disease. In patients with distant metastases, it was also higher than in those without. Increase in serum ProGRP31-98 and NSE was both seen in SCLC patients, but the former was of much greater magnitude when compared to the normal controls. Given the cut-off levels of 40 pg/ml for ProGRP31-98 and 8 micrograms/L for NSE, their sensitivity of diagnosis in SCLC was 73% and 60%, respectively. The area under ROC curve of ProGRP31-98 was significantly larger than that of NSE. Similar results of diagnostic sensitivity and area under ROC curve were observed in SCLC patients with limited disease. All patients responded to chemotherapy showed marked decrease in ProGRP31-98. CONCLUSION: ProGRP31-98 is a more specific and sensitive marker than NSE for the diagnosis of SCLC.
UI - 11798192
AU - Zhang Y; Thant AA; Hiraiwa Y; Naito Y; Sein TT; Sohara Y; Matsuda S;
TI - Hamaguchi M A role for focal adhesion kinase in hyluronan-dependent MMP-2 secretion in a human small-cell lung carcinoma cell line, QG90.
SO - Biochem Biophys Res Commun 2002 Jan 25;290(3):1123-7
AD - Laboratory of Molecular Pathogenesis, Nagoya University School of Medicine, Showaku, Nagoya, 466-8550, Japan.
Hyluronan (HA), a nonsulfated high-molecular mass glycoaminoglycan, has been assigned as a clinical marker for the progression of various tumors. We found that HA stimulation of QG90, a cell line derived from human small-cell lung carcinoma, activates the secretion of matrix metalloproteinase-2 (MMP-2) in a focal adhesion kinase (FAK)-dependent manner. HA stimulation of QG90 cells activated MMP-2 secretion in a time-dependent manner. Larger sizes of HA seemed to have higher activities than smaller size one in MMP-2 secretion. Under HA stimulation, tyrosine phosphorylation of cellular proteins including FAK was activated. By use of antisense oligonucleotide to FAK, we found that FAK signaling was required for the activation of MMP-2 secretion and for the sustained activation of MAP kinase by HA treatment. These results strongly suggest that FAK-MAPK signaling is involved, at least in part, in HA-dependent activation of MMP-2 secretion in QG90 cells.
UI - 11826488
AU - Gorbunova VA; Orel NF; Semina OV; Besova NS; Kadagidze ZG
TI - [Nitrullin -- a new original Russian drug of the nitrosomethylurea group]
SO - Vopr Onkol 2001;47(6):680-3
AD - N.N. Blokhin Center for Oncology Research, Russian Academy of Medical Sciences, Moscow.
Hematologic thrombopenia and leukopenia formation limits use of nitrullin as a toxic hazard. The drug showed moderate effect in treating inoperable non-small cell cancer of the lung and satisfactory end results. The treatment had marked symptomatic effect in patients with this cancer and, as a consequence, improved the quality of life. Nutrullin had immuno-modulating effect. Its application alone or in combination with VPN showed good results in the management of small-cell cancer of the lung.
UI - 11710837
AU - Pedersen MW; Thykjaer T; Orntoft TF; Damstrup L; Poulsen HS
TI - Profile of differentially expressed genes mediated by the type III epidermal growth factor receptor mutation expressed in a small-cell lung cancer cell line.
SO - Br J Cancer 2001 Oct 19;85(8):1211-8
AD - Department of Radiation Biology, The Finsen Centre, National University Hospital, Section 6321, Copenhagen, DK-2100, Denmark.
Previous studies have shown a correlation between expression of the EGF receptor type III mutation (EGFRvIII) and a more malignant phenotype of various cancers including: non-small-cell lung cancer, glioblastoma multiforme, prostate cancer and breast cancer. Thus, a detailed molecular genetic understanding of how the EGFRvIII contributes to the malignant phenotype is of major importance for future therapy. The GeneChip Hu6800Set developed by Affymetrix was used to identify changes in gene expression caused by the expression of EGFRvIII. The cell line selected for the study was an EGF receptor negative small-cell-lung cancer cell line, GLC3, stably transfected with the EGFRvIII gene in a Tet-On system. By comparison of mRNA levels in EGFRvIII-GLC3 with those of Tet-On-GLC3, it was found that the levels of mRNAs encoding several transcription factors (ATF-3, JunD, and c-Myb), cell adhesion molecules (CD36, CD24), signal transduction related molecules (MKP-1) and other molecules related to cancer (CD98, thymosin beta-10) were altered in the EGFRvIII transfected cell line. Northern hybridisations and Western blot analyses were used to verify selected results. The results indicate that expression of EGFRvIII alters expression of genes involved in the control of cell growth, survival and motility. Copyright 2001 Cancer Research Campaign http://www.bjcancer.com.
UI - 11783071
AU - Huang X; Li L; Guo Z
TI - [Immunoelectron microscopic analysis of P-glycoprotein, p53, and Bcl-2 proteins expressions in lung cancer]
SO - Zhonghua Zhong Liu Za Zhi 2001 Jan;23(1):53-6
AD - Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China.
OBJECTIVE: To determine the ultrastructural localization of P-gp, p53 protein, and Bcl-2 protein in lung cancer cells, their relation to multidrug resistance and possible mechanisms of action. METHODS: Expression of P-gp, p53, and Bcl-2 proteins was examined in 8 NSCLC surgical specimens and 7 SCLC bronchoscopically biopsied specimens using postembedding PAG immunolabelling technique for electron microscopy. RESULTS: P-gp was detected on the cell membrane and the periphery of endoplasmic reticulum (ER). P53 protein was observed not only in the nuclei associated with heterochromatin but also in the cytosol. Bcl-2 protein immunoreactivity was associated with mitochondria and ER. P-gp, p53, and Bcl-2 were detected in 5(33%), 9(60%), and 4 (26.7%) out of the 15 samples examined, respectively. In 8 normal lung tissues, these three proteins were detected. Of 5 P-gp positive samples 4 were NSCLC, only 1 was SCLC after chemotherapy. CONCLUSION: P-gp, p53, and Bcl-2 proteins are detectable immuno-electron microscopically in lung cancer cells. No correlation in expression existed between of p53 and P-gp, nor did that between p53 and Bcl-2. The plasma membrane localization of P-gp supports its action as a transmembrane drug efflux pump. P-gp may play a role in MDR in lung cancer.
UI - 11783073
AU - Han Y; Yuan Y; Chu J
TI - [Detection and diagnosis of small peripheral lung cancers less than 15 mm in diameter]
SO - Zhonghua Zhong Liu Za Zhi 2001 Jan;23(1):60-3
AD - Department of Radiology, Dalian University Affiliated Central Hospital, Dalian 116033, China.
OBJECTIVE: To assess the value of chest film, conventional CT (CCT), Spiral CT (SCT) and high resolution CT (HRCT) for detection and diagnosis of small peripheral lung cancers less than 15 mm in diameter. METHODS: Chest film, CCT, SCT and HRCT were taken in 59 cases of peripheral lung cancers less than 15 mm in diameter confirmed by operation and pathology. Their value in the diagnosis was analysed retrospectively. RESULTS: In 47% of chest films and 17% of CCT, the small lung cancer was not detected. However no tumor escaped detection by SCT. HRCT was superior for showing density and detailed image signs compared to chest film and CCT. The CT features of small peripheral lung cancers was different from those of larger peripheral lung cancers. CONCLUSION: The SCT is the best method for detection, and HRCT for diagnosis of small peripheral lung cancers less than 15 mm in diameter.
UI - 11697833
AU - Skarlos DV; Samantas E; Briassoulis E; Panoussaki E; Pavlidis N;
TI - Kalofonos HP; Kardamakis D; Tsiakopoulos E; Kosmidis P; Tsavdaridis D; Tzitzikas J; Tsekeris P; Kouvatseas G; Zamboglou N; Fountzilas G Randomized comparison of early versus late hyperfractionated thoracic irradiation concurrently with chemotherapy in limited disease small-cell lung cancer: a randomized phase II study of the Hellenic Cooperative Oncology Group (HeCOG).
SO - Ann Oncol 2001 Sep;12(9):1231-8
AD - Athens Medical Center, Greece. email@example.com
BACKGROUND: Concurrent platinum etoposide chemotherapy given in combination with hyperfractionated thoracic radiation therapy (HTRT) in limited disease (LD) small cell lung cancer (SCLC) is associated with a high response rate and significant prolongation of survival. Given these results, the Hellenic Cooperative Oncology Group (HeCOG) performed a multicenter randomized phase II study in patients with LD SCLC to evaluate the timing of HTRT (early vs. late) when given concurrently with chemotherapy. PATIENTS AND METHODS: To be eligible for the study, patients were required to have histologically or cytologically proven LD SCLC, confined to one hemithorax and/or ipsilateral mediastinal or supraclavicular lymphnodes and absence of pleural effusion or controlateral supraclavicular lymphnode involvement. Moreover, patients had to have a good performance status and adequate haematological, liver and renal function. Patients with LD SCLC were randomized to receive HTRT either concurrently with the first (Group A) or with the fourth (Group B) cycle of chemotherapy. Chemotherapy consisted of carboplatin administered at an AUC of six given as an i.v. 1-hour-infusion immediately followed by etoposide at a dose of 100 mg/m2 i.v. as a two-hour infusion for three consecutive days every three weeks up to a total of six cycles. Prophylactic cranial irradiation was also given to patients achieving a complete response. RESULTS: 42 and 39 patients, were eligible for efficacy evaluation in group A and B respectively. The overall response rate was 76% in group A and 92.5% in group B (P = 0.07) with a complete response rate of 40.5% and 56.5%, respectively. After a median follow-up of 35 months, time to progression was 9.5 months in group A and 10.5 in group B (NS) while overall median survival was 17.5 and 17 months respectively (NS). The 2-year survival was 36% in group A and 29% in group B (NS) and the 3-year survival 22% and 13%, respectively (NS). The distant relapse rate was 38% in group A and 61% in group B (P = 0.046). Severe grade 3 4 anemia was recorded in 19% of group A and 12.5% of group B (NS), while severe leucopenia was recorded in 35.5% and 20.5% (P = 0.09) and neutropenic fever in 5% and 2.5% (NS), respectively. Severe thrombocytopenia did not differ significantly between the two treatment groups being 21.5% and 23%, respectively. Severe grade 2-3 esophageal toxicity was 19% in group A and 23% in group B (NS), while grade 3 lung toxicity was 5% and 7.5% (NS), respectively. No toxicity-related deaths were recorded. CONCLUSION: Concurrent administration of HTRT with carboplatin etoposide is associated with a high response and survival rate. Although a trend for higher response rate was recorded in the group of patients who received late HTRT, the overall median, 2-year and 3-year survival rates did not differ significantly between the two treatment groups. The toxicity of this promising therapeutic approach was acceptable. Comparative phase III studies with an adequate number of patients are recommended in order to answer this question.
UI - 11783024
AU - Feng F; He X; Shi Y
TI - [Clinical study of topotecan in the treatment of small cell lung cancer and recurrent ovarian cancer]
SO - Zhonghua Zhong Liu Za Zhi 2001 Mar;23(2):155-8
AD - Cancer Institute (Hospital), Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100021, China.
OBJECTIVE: To evaluate the effect and adverse reaction of China made topotecan in the treatment of small-cell lung cancer (ACLC) and recurrent ovarian cancer (OV). METHODS: From January to July, 2000, topotecan was used to treat 141 patients at a dose of 1.2 mg/m2, given daily as 30-min i.v. infusion for 5 days. Treatment was repeated once every 3 weeks. Of the 141 patients, 118 were evaluable for therapeutic efficacy. All the patients received a total of 286 cycles of treatment were assessable for analysis of adverse reactions. RESULTS: Among the evaluable patients, there were 5 CR, 35 PR, with an overall response rate (RR) of 33.8%. There were 3 CR and 26 PR in 89 patients with SCLC (RR 32.5%). The response rate of patients with or without prior chemotherapy was 15.6% and 50%, respectively. In 29 patients with recurrent OV, there were 2 CR and 9 PR (RR 37.9%). The major toxic effect was myelosuppression. Non-hematopoietic toxicities were mild and tolerable. CONCLUSION: Topotecan is an effective drug for the treatment of SCLC and recurrent OV. It is still efficacious in some patients who previously received standard chemotherapy. The major dose-limiting toxicity is myelosuppression. The response rate and toxicity of the domestically made topotecan are comparable with those of the imported one.
UI - 11783029
AU - Li Q; Zhou J; Qu F
TI - [A comparative clinical study of carboplatin solution and carboplatin powder]
SO - Zhonghua Zhong Liu Za Zhi 2001 Mar;23(2):170-2
AD - Department of Medical Oncology, Cancer Institute (Hospital), Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100021, China.
OBJECTIVE: To observe the efficacy and side effects of carboplatin solution in comparison with carboplatin powder. METHODS: A multicenter, open randomized controlled trial was carried out. A total of 121 patients with small cell lung cancer (SCLC), non-small cell lung cancer (NSCLC) and breast cancer (BC) were randomized into carboplatin injection group (study group) and carboplatin powder group (control group), treated with CE, CIE and CAF protocol, respectively. The same drugs and dosage were used in the two groups. RESULTS: The response rate of the study group and the control group was 94% and 67% in SCLC (P > 0.05), 12% and 22% in NSCLC (P > 0.05) and 71.4% and 67% in BC (P > 0.05), respectively. The major side effects were myelosuppression and gastrointestinal reactions, the frequency and intensity of which were statistically not different in the 2 groups of patients. CONCLUSION: Carboplatin solution is as effective as carboplatin powder for the treatment of cancer.
UI - 11748482
AU - Milman N; Pedersen LM
TI - The serum ferritin concentration is a significant prognostic indicator of survival in primary lung cancer.
SO - Oncol Rep 2002 Jan-Feb;9(1):193-8
AD - Department of Pulmonary Medicine, Naestved Hospital, DK-4700 Naestved, Denmark. firstname.lastname@example.org
The prognostic significance of serum ferritin on survival in lung cancer was evaluated. One hundred and ninety-seven patients were referred for evaluation of pulmonary lesions; 115 patients (85 men) had primary lung cancer. Their median age was 57 years. Seventy-four patients (43 men) with benign lung disease were enrolled as controls. Their median age was 53 years. Serum ferritin was measured at diagnosis. Non-small cell lung cancer (NSCLC) (n=90) was graded according to the TNM-system and small cell lung cancer (SCLC) (n=25) in limited and extensive disease. Follow-up was median 30 months (range 23-36). Patients with lung cancer had higher median ferritin than controls (245 vs. 145 microg/l, p<0.00001): the prevalence of ferritin >300 microg/l was 37% in patients with lung cancer and 14% in controls (p<0.001). There was no significant difference in ferritin between patients with different stages either in NSCLC or in SCLC. Patients with SCLC had higher median ferritin than patients with NSCLC (344 vs. 233 microg/l, p<0.05). No significant differences in ferritin could be demonstrated among the other histological tumour types. The overall survival rate in patients with lung cancer was 52% after 1 year, 33% after 2 years, and 13% after 3 years. Survival rate was lower in patients with ferritin >300 microg/l than in those with ferritin < or =300 microg/l (p<0.0001). The probability of survival 1, 2 and 3 years after diagnosis in patients with ferritin >300 microg/l was 36, 20 and 4%, respectively, and in patients with ferritin < or =300 it was 63, 42 and 18%, respectively (p<0.0001). An elevated ferritin was a significant prognostic factor (p<0.01) even after adjustment for performance status, age, sex, TNM stage, and histological tumour type. TNM stage and performance status were likewise predictors of survival (p<0.01 and p<0.001, respectively). There exists a clinically relevant relationship between serum ferritin concentration and the prognosis of survival in patients with primary lung cancer. The routine use of serum ferritin should be considered in the evaluation and follow-up of pulmonary malignancies.
UI - 11748453
AU - Kakihana M; Yahata N; Hirano T; Honda H; Ikeda N; Kawate N; Konaka C;
TI - Ebihara Y; Ohyashiki K; Kato H Telomerase activity during carcinogenesis in the bronchus.
SO - Oncol Rep 2002 Jan-Feb;9(1):43-9
AD - First Department of Surgery, Tokyo Medical University School of Medicine, Shinjuku-ku, Tokyo 160-0023, Japan. email@example.com
Telomerase is a ribonucleoprotein reverse transcriptase that synthesizes telomeric DNA onto chromosome ends, and is not detected in most normal cells. It has been clarified that some bronchial squamous cell carcinomas may arise through the metaplasia and dysplasia sequence accompanied by accumulation of genetic mutations in metaplastic cells. Recently a highly sensitive polymerase chain reaction (PCR)-based telomerase assay (TRAP assay) was developed for the detection of telomerase activity. Telomerase activity has been found in most malignant neoplasms, including lung cancer. The objective of this study was to determine whether telomerase RNA might increase in precancerous lesions of the bronchi. Bronchial-brushing extracts were analyzed for telomerase activity (F-TRAP) and in situ telomerase activity using a fluorescence-based TRAP assay (in situ TRAP) and compared to cytological features. The fluorescence-based semi-quantitative TRAP assay detected telomerase activity in 8 out of 12 lung cancer cases (66.7%). In squamous cell carcinoma, 6 out of 9 cases (66.7%) showed telomerase activity. On the other hand, in normal and precancerous lesions of the bronchi, telomerase activity was not detected using either the F-TRAP method or in situ TRAP method. We concluded that dysplastic cells might not contain immortalized cells, and that the increase of telomerase activity is a relatively late event during the bronchial carcinogenesis. It is difficult to distinguish between dysplasia and in situ carcinoma of the bronchus morphologically, but the measurement of telomerase activity is clinically valuable for the determination of treatment.
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