National Cancer Institute®
Last Modified: June 1, 2002
UI - 11971207
AU - Cho ES; Chang J; Chung KY; Shin DH; Kim YS; Kim SK; Kim SK
TI - Identification of tumor suppressor loci on the long arm of chromosome 4 in primary small cell lung cancers.
SO - Yonsei Med J 2002 Apr;43(2):145-51
AD - Department of Internal Medicine and Cancer Metastasis Research Center, Yonsei University College of Medicine, C.P.O. Box 8044, Seoul 120-752, Korea.
Recent cytogenetic studies have indicated that loss of the long arm of chromosome 4 is a frequent event in small cell lung cancer (SCLC), which suggests the presence of tumor suppressor genes there. To precisely map tumor-suppressor loci on chromosome 4q for further positional cloning efforts, we tested 15 primary SCLCs. Forty two polymorphic microsatellite markers located on chromosome 4q were used in the microsatellite analysis. We found that 12 (80%) of the 15 tumors exhibited loss of heterozygosity (LOH) in at least one of the tested microsatellite markers, and that 3 (25%) of these 12 tumors exhibited a larger area of deletion on chromosome 4q. Frequent LOH, defined as occurring in more than 50% of the tumors, was observed in five commonly deleted regions on 4q, namely 4q24, 4q27-28.3, 4q33, 4q34.1, and 4q34.3-35.2. Of these 5, LOH at 4q33 was the most frequent (61.5%). Six (40%) of the 15 tumors exhibited shifted bands in at least one of the tested microsatellite markers. Shifted bands occurred in 3.7% (23 of 630) of the loci tested. Our data demonstrated that at least five tumor-suppressor loci exist on the long arm of chromosome 4 and that they may play an important role in the development and progression of primary small cell lung cancer tumorigenesis.
UI - 12000707
AU - Graff L; Frungieri M; Zanner R; Pohlinger A; Prinz C; Gratzl M
TI - Expression of histidine decarboxylase and synthesis of histamine by human small cell lung carcinoma.
SO - Am J Pathol 2002 May;160(5):1561-5
AD - Anatomisches Institut, Universitat Munchen, Munchen, Germany.
We recently found that human small cell lung carcinomas (SCLCs) express, in addition to other neuroendocrine markers, vesicular monoamine transporters. Our present results indicate that SCLCs are histaminergic. We detected the biosynthetic enzyme histidine decarboxylase by immunohistochemistry in paraffin sections of 12 biopsies of SCLC tumors. This finding was supported by immunoblotting and reverse transcription-polymerase chain reaction experiments using established SCLC cell lines, frozen and paraffin-embedded SCLC tumors. Moreover, we found histamine to be synthesized, stored, and released by cultured SCLC cells. Our novel observations may be useful for developing new diagnostic tools for this frequent and highly malignant tumor.
UI - 11844602
AU - Uno T; Sumi M; Ikeda H; Teshima T; Yamashita M; Inoue T; Japanese PCS
TI - Working Subgroup of Lung Cancer Radiation therapy for small-cell lung cancer: results of the 1995-1997 patterns of care process survey in Japan.
SO - Lung Cancer 2002 Mar;35(3):279-85
AD - Department of Radiation Oncology, School of Medicine, Chiba University, Inohana 1-8-1, Chuou-ku, Chiba City, Chiba 260-8670, Japan. firstname.lastname@example.org
The Patterns of Care Study (PCS) conducted a nationwide audit survey in order to establish the national practice process of radiation therapy for small-cell lung cancer (SCLC) and examined the influence of institutional stratification on the process of care in Japan. The PCS randomly sampled institutions and patients using a two-stage cluster method and surveyed the process of radiation therapy for 174 stage I-III SCLC patients according to the category of institution, stratified as follows: A1, academic institutions treating > or = 300 patients a year; A2, <300 patients; B1, non-academic institutions treating > or = 120 patients a year; and B2, <120 patients. Karnofsky performance status distributions showed significant variance by stratification of institutions (P=0.013). Patients treated on an outpatient basis accounted for 32% in A1, 23% in A2, 8% in B1, but only 5% in B2 (P=0.007). A photon energy > or = 10 MV was used for 87% of patients in A1, 69% in A2, 54% in B1 and 23% in B2 (P=0.001). Contralateral hilus was irradiated for 11% of patients in A1, 17% in A2, 29% in B1 and 3% in B2 (P=0.001). Field size reduction during the treatment course was done for 77% of patients in A1, 54% in A2, 60% in B1 and 42% in B2 (P=0.007). Ninety-two percent of patients received combined chemotherapy and radiation therapy, and the most frequently used drugs were etoposide (91%) and cisplatin (69%). The results of clinical studies on SCLC had favorably penetrated into the clinical practice. However, the stratification of institutions significantly affected the process of radiation therapy in Japan.
UI - 12022548
AU - Saito Y; Yamakawa Y; Kiriyama M; Fukai I; Kondo S; Kaji M; Yano M;
TI - Yokoyama T; Fujii Y Diagnosis of visceral pleural invasion by lung cancer using intraoperative touch cytology.
SO - Ann Thorac Surg 2002 May;73(5):1552-6; discussion 1556-7
AD - Department of Surgery II, Nagoya City University Medical School, Nagoya, Japan.
BACKGROUND: Invasion to the visceral pleura is an important component of lung cancer staging and an independent prognostic factor. However, the accuracy of pathologic examination depends on how the sections are made, and the pathologist may miss the most invaded part of the pleura. Therefore, we have designed "touch" cytology in an effort to more accurately diagnose the pleural invasion by lung cancer. METHODS: Immediately after thoracotomy, the surface of the visceral pleura just above the tumor was gently touched by a glass slide without scrubbing in 100 patients who simultaneously underwent pleural lavage cytology or cytology of the subclinical pleural effusion. RESULTS: Seventeen percent of the tumors were diagnosed as invading the visceral pleura by touch cytology. Lavage cytology was found to be positive in 7%. In reference to the pathologic examination of the tumor specimen, touch cytology was found to be positive in all of p3, 5 out of 6 of p2, 5 out of 30 of p1, and 5 out of 62 of p0 cases. Touch cytology correctly diagnosed all the positive cases detected by lavage or effusion cytology. CONCLUSIONS: This study suggests that our method is useful in detecting the visceral pleural invasion and raises a possibility that pathologic p0 and p1 lung cancers include a subset of patients with tumor cells exposed on the pleural surface.
UI - 11888669
AU - Sadava D; Phillips T; Lin C; Kane SE
TI - Transferrin overcomes drug resistance to artemisinin in human small-cell lung carcinoma cells.
SO - Cancer Lett 2002 May 28;179(2):151-6
AD - Keck Science Center, 925 N. Mills Avenue, Claremont, CA 91711, USA. email@example.com
Multiple drug resistance is a significant problem in small-cell lung cancer (SCLC). Artemisinin (ART) is a natural product used to treat drug-resistant malaria. The drug is effective because the Fe2+ present in infected erythrocytes acts non-enzymatically to convert ART to toxic products. We tested the effects of ART on drug-sensitive (H69) and multi-drug-resistant (H69VP) SCLC cells, pretreated with transferrin (TF) to increase the intracellular Fe2+ level. Antibody staining followed by flow cytometry analysis showed twice the level of TF receptors on the H69VP as compared to the H69 cells. Low doses of ART were cytotoxic to SCLC cells. The cytotoxicity of ART for H69VP cells (IC50=24 nM) was ten-fold lower than for H69 cells (IC50=2.3 nM), indicating that ART is part of the drug resistance phenotype. Pretreatment of H69 cells with 220-880 nM TF did not alter the IC50 for ART. However, in the ART-resistant H69VP cells, pretreatment with TF lowered the ART IC50 to near drug-sensitive levels (IC50=5.4 nM after 4 h pretreatment with 880 nM TF). Desferrioxamine (5 microM) inhibited the effect of TF on the IC50 for ART in drug-resistant cells but did not have an effect on ART cytotoxicity in drug-sensitive cells. DNA fragmentation as measured by ELISA occurred within ART-treated cells, with kinetics indicating apoptosis rather than necrosis. This was confirmed by TUNEL staining. These data indicate the potential use of ART and TF in drug-resistant SCLC.
UI - 11989256
AU - Fukuoka M
TI - [Progress in diagnosis and treatment of lung cancer]
SO - Nippon Naika Gakkai Zasshi 2002 Mar 20;91 Suppl():15-22
UI - 12040671
AU - Tsuboi M; Kato H
TI - [Current status of the chemotherapy for lung cancer]
SO - Gan To Kagaku Ryoho 2002 May;29(5):684-94
AD - Dept. of Surgery, Tokyo Medical University.
In the treatment of limited-stage small cell lung cancer (LD-SCLC) and unresectable locally-advanced non-small cell lung cancer, several phase III trials and meta-analysis have demonstrated the following: 1) combining chemotherapy and thoracic irradiation is better than chemotherapy alone or radiotherapy alone, 2) the concurrent use of chemoradiotherapy has been expected a better survival than the sequential use, 3) the improvement in outcome seen with a concurrent chemoradiotherapy approach may be because of spatial cooperation, enhanced radiosensitization, and/or enhanced cytotoxicity, and 4) the chemoradiotherapy is tolerable without significant morbidities, such as pneumonitis and esophagitis. However, the chemoradiotherapy is still an investigational strategy because of the absence of a definite schedule and dose on radiotherapy. Newer, more tolerable chemotherapeutic agents, molecular biologic novel approaches and newer irradiated procedures are now being investigated.
UI - 12040679
AU - Tada A; Ueoka H; Kiura K; Tabata M; Takemoto M; Yamane H; Hiyama J; Aoe
TI - K; Shibayama T; Kamei H; Kawahara S; Harita S; Sato T; Kobayashi M; Eguchi K; Hiraki S; Hiraki Y; Tanimoto M [Combination chemotherapy with carboplatin and etoposide for elderly patients aged 76 years or older with small cell lung cancer]
SO - Gan To Kagaku Ryoho 2002 May;29(5):751-6
AD - Dept. of Internal Medicine, National Minami-Okayama Hospital.
Eighteen elderly patients aged 76 years or older with small cell lung cancer were treated with carboplatin (AUC = 4 mg/ml.min, i.v. day 1) and etoposide (70 mg/m2 i.v. day 1-3) and 17 patients were evaluable. The median age of the study population was 77 years (range: 76-81). Eight patients had limited disease (LD) and nine did extensive disease (ED). The overall response rate was 88% for LD patients and 67% for ED patients. Median survival time was 219 days for LD patients and 158 days for ED patients. Grade 3 and 4 leukopenia, neutropenia, thrombocytopenia and anemia occurred in 41%, 76%, 24% and 6% of patients, respectively. There was one treatment-related death due to pneumonitis.
UI - 11905738
AU - Rintoul RC; Sethi T
TI - The role of extracellular matrix in small-cell lung cancer.
SO - Lancet Oncol 2001 Jul;2(7):437-42
AD - Centre for Inflammation Research, University of Edinburgh, UK.
Lung cancer is the most common fatal malignant disease in the western world, accounting for 42,000 deaths each year in the UK alone. Small-cell lung cancer (SCLC), accounts for 25% of all lung cancers. It is a particularly aggressive form of the disease, characterised by widespread metastases and the development of resistance to chemotherapy. Even with combination chemotherapy and radiotherapy treatments, the 5-year survival is only about 5%. We review recent insights into the mechanisms underlying the development of metastases and resistance to chemotherapeutic agents in SCLC, focusing on the role of the extracellular matrix (ECM). We discuss the regulation of the interactions between cells and the ECM and the effects of these interactions on cellular phenotypes, together with some of the new approaches for combating drug resistance and metastases in this disease.
UI - 11911315
AU - Gridelli C; Curcio C; Iaffaioli RV; Brancaccio L; D'Aprile M; Gebbia V;
TI - Rossi A; Tortoriello A; Veltri E; Maione P; Barbarisi A; Gallo C; Guida C; Perrone F Carboplatin + epirubicin +VP-16 + lenograstim followed by radiotherapy + carboplatin as radiosensitizer in limited small cell lung cancer. A multicenter phase II study.
SO - Anticancer Res 2001 Nov-Dec;21(6A):4179-83
AD - Oncologia Medica B, Istituto Nazionale Tumori, Napoli, Italy. firstname.lastname@example.org
A phase II trial was undertaken to test the activity and toxicity of carboplatin (300 mg/m2, i.v. day 1) + epirubicin (75 mg/m2, i.v. day 1) + VP-16 (100 mg/m2, i.v. days 1 to 3) + lenograstim (5 mcg/kg, s.c. days 6 to 15) administered every 3 weeks for 4 cycles and subsequent chest irradiation (50 Gy) + daily carboplatin (25 mg/m2) in the first-line treatment of adults affected by limited small cell lung cancer (SCLC). PATIENTS AND METHODS: A single-stage phase II design was used; the complete response (CR) rate after chest radiotherapy was the primary end-point. Twenty-three CRs were required out of 38 patients to consider the treatment worthy of further study. Prophylactic cranial irradiation (PCI) was planned in case of CR. Patients aged < or = 70 were eligible if they had limited SCLC, a performance status not worse than 2 by the ECOG scale and no prior chemotherapy or radiotherapy. RESULTS: From was 60 years. All the patients started chemotherapy; 23 patients received chest irradiation and concurrent daily carboplatin; 11 patients also received PCI. Toxicity was generally mild. Sixteen CRs (48.5%, 95% CI: 30.8-66.5) were recorded; the objective response rate was 72.7% (95% CI: 54.5-86.7). The median time-to-progression was 7.9 months (95% CI: 6.5-10.4). The median-survival was 10.7 months (95% CI: 9.2-16.1). CONCLUSION: Induction chemotherapy with carboplatin + epirubicin + VP-16 followed by chest irradiation plus concurrent daily carboplatin is well-tolerated but not sufficiently active to warrant further study in the treatment of patients with limited SCLC.
UI - 12033195
AU - Hainsworth JD; Morrissey LH; Scullin DC Jr; Houston GA; Prasthofer EF;
TI - Gray JR; Burris HA 3rd; Greco FA Paclitaxel, carboplatin, and topotecan in the treatment of patients with small cell lung cancer: a phase II trial of the Minnie Pearl Cancer Research Network.
SO - Cancer 2002 May 1;94(9):2426-33
AD - The Sarah Cannon Cancer Center, Nashville, Tennessee 37203, USA. email@example.com
BACKGROUND: The objective of this study was to evaluate the feasibility, toxicity, and efficacy of a novel three-drug regimen containing paclitaxel, carboplatin, and topotecan followed by oral etoposide in the first-line treatment of patients with small cell lung carcinoma. METHODS: One hundred five patients with previously untreated, limited stage or extensive stage small cell lung carcinoma were treated in this multicenter, community-based, Phase II trial. All patients received paclitaxel 135 mg/m(2) by 1-hour intravenous (i.v.) infusion on Day 1, carboplatin at an area under the serum concentration-time curve of 5.0 i.v. on Day 1, and topotecan 0.75 mg/ m(2) i.v. on Days 1-3. The treatment regimen was repeated at 21-day intervals for 4 courses. Patients with limited stage disease also received radiation therapy (45 grays [Gy]; in single daily fractions of 1.8 Gy) beginning concurrently with the third course of chemotherapy. Patients who had an objective response or stable disease after 4 courses of combined paclitaxel, carboplatin, and topotecan then received 3 courses of oral etoposide (50 mg alternating with 100 mg for 10 consecutive days) repeated at 21-day intervals. RESULTS: Treatment with paclitaxel, carboplatin, and topotecan produced response rates of 88% and 93% in patients with extensive stage disease and limited stage disease, respectively. The median survival for patients with extensive stage and limited stage disease was 8.3 months and 17.2 months, respectively. The addition of oral etoposide was feasible, but there was no suggestion that it prolonged remission. This three- drug regimen was associated with acceptable toxicity in patients with a good performance status, although it was tolerated very poorly by patients with an Eastern Cooperative Oncology Group performance status of 2; 5 of 12 patients (42%) had treatment-related deaths. CONCLUSIONS: Although this three-drug regimen was active in the treatment of patients with small cell lung carcinoma, it was more toxic than standard platinum and etoposide regimens and provided no apparent improvement in efficacy. Further investigation of topotecan as a component of first-line therapy should focus on two-drug combination regimens in which the topotecan dose can be optimized. Routine use of three-drug regimens in patients with small cell lung carcinoma should await demonstration of superiority in randomized trials.
UI - 12032850
AU - Bangur CS; Switzer A; Fan L; Marton MJ; Meyer MR; Wang T
TI - Identification of genes over-expressed in small cell lung carcinoma using suppression subtractive hybridization and cDNA microarray expression analysis.
SO - Oncogene 2002 May 23;21(23):3814-25
AD - Tumor Antigen Discovery, Corixa Corporation, 1124 Columbia Street, Seattle, Washington WA 98104, USA. firstname.lastname@example.org
To identify genes that are differentially over-expressed in Small Cell Lung Carcinoma (SCLC) we have used a combination of suppression subtractive hybridization and cDNA microarray to analyse the expression profiles of 2400 cDNAs clones. Genes that are over-expressed in SCLC were identified using 32 pairs of fluorescence-labeled cDNA samples representing various lung tumors and normal tissues. This comprehensive approach has resulted in the identification of 209 genes that are differentially over-expressed in SCLC. Quantitative real-time PCR was used to further validate the expression of 43 genes in SCLC tumors and various normal tissues. Discussed in this report are nine genes, which showed the most promising SCLC tumor to normal tissue differential expression profiles, including seven known and two novel genes. The large number of differentially expressed genes identified from this analysis and the characterization of these genes will provide valuable information in better understanding the biology of SCLC and help us in developing these gene products as potential targets for diagnostic as well as therapeutic usage.
UI - 12040757
AU - Slanina J; Laubenberger J
TI - CT-based study on potential mediastinal lymph node spread of patients with lung cancer. Contribution to 3-D treatment planning for adjuvant radiotherapy of the mediastinum.
SO - Strahlenther Onkol 2002 Apr;178(4):199-208
AD - Department of Radiation Therapy, Radiological University Clinic, Freiburg, Germany. email@example.com
AIMS: To provide a schematized and graduated CT reference series of the mediastinum showing CT-detectable lymph node areas of lung cancer patients to support 3-D treatment planning and documentation for adjuvant irradiation of the mediastinum. PATIENTS AND METHODS: Cross sections of mediastinal structures from one male individual were schematized and overlaid with a 1 cm2 reference grid. Mediastinal CT scans of 100 consecutive patients with histologically proven lung cancer and CT-detectable lymph nodes were evaluated. For each patient the outlines of all identifiable nodes were transferred into the schematized CT series according to their localization in relation to anatomical landmarks. The outlines were centered in a predefined way into relevant squares of the reference grid. The number of patients with nodes projecting to individual CT cross sections was determined. Further, the number and percentage of patients locating to positive grid squares were analyzed. RESULTS: A differentiated pattern of CT-detectable lymph nodes was confirmed. Along the longitudinal axis the CT-detectable nodes followed a Gaussian distribution with its maximum (89% of all patients) at the level of the tracheal bifurcation. At different transverse levels closely circumscribed central areas with node positive grid squares were identified harboring up to 72% of the patients (locating to the front of the trachea, the bifurcation and below the carina). Peripheral areas showed only sporadically node positive grid squares, usually representing less than 5% of the patients. CONCLUSIONS: These schematized and graduated CT cross sections show areas of CT-detectable lymph node spread from the view of 3-D planning. They are of additional help to individualize mediastinal target volumes and/or dose distributions, particularly when administering adjuvant irradiation to patients without mediastinal lymph node involvement. Classifying mediastinal structures by using a grid square easily allows to describe and document target volumes and dose distributions per cross section.
UI - 12016035
AU - Depierre A; Jacoulet P; Westeel V; Falcoz PE
TI - [To be cured of lung cancer]
SO - Bull Cancer 2002 Apr;89(4):351-6
AD - Service de pneumologie, Hopital Jean-Minjoz, boulevard Fleming, 25030 Besancon Cedex, France.
Pronostic of lung carcinoma is very poor but, every year in Europe and North America, thousands of patients are offered a chance of cure. However only a long period of time without relapse allows to state the reality of cure. Sequelae generated by cancer treatments are potentially increased by the use of treatments combinations. In operated patients, chronic respiratory insufficiency is the most common late complication often interfering with professionnal activity especially for manual workers. Late toxicity after radiotherapy for lung cancer has been little studied. Thoracic irradiation especially affects lung and cardiac functions. Late toxicity of chemotherapy may be more frequent with the increasing use of neoadjuvant chemotherapy before surgery or radiotherapy in patients potentially cure.
UI - 11820634
AU - Rybacka-Chabros B; Mandziuk S; Berger-Lukasiewicz A; Danko-Mrozinska M;
TI - Milanowski J The coexistence of tuberculosis infection and lung cancer in patients treated in pulmonary department of Medical Academy in Lublin during last ten years (1990-2000).
SO - Folia Histochem Cytobiol 2001;39 Suppl 2():73-4
AD - Pulmonary Department, Medical Academy, Lublin, Poland.
The coexistance of tuberculous infection (TB-infection) and lung cancer in patients treated in Pulmonary Department of Medical Academy in Lublin during last ten years (1990-2000) has been evaluated. Inclusion criteria involved: aging from 50 to 80 years, tobacco smoking, tuberculous infection in present or in past, lung cancer. All analyzed patients (32 males, 13 females) were heavy smokers (from 10 to 70 cigarettes per day, during at least 5 years). 27 patients were suffered from lung tuberculosis in past, the rest of them had active tuberculous infection. In 19 cases we detected carcinoma planoepitheliale, in 13 cases carcinoma macrocellulare, in 7 cases carcinoma microcellulare and in 6 cases adenocarcinoma. We concluded, that increased occurrence of lung cancer in TB reinfected patients may be connected with immunodepression caused by chronic TB infection. In patients with new active TB-infection in whom the clinical status and chest X-ray were getting worse in spite of antituberculotic treatment recommended procedures for cancer diagnosis were performed. We suggest that bad results of anti-tuberculotic treatment in TB-infected patients are not always caused by bactericidal resistance. In these cases, the proper diagnosis of lung cancer should be considered.
UI - 11914104
AU - Rintoul RC; Sethi T
TI - Extracellular matrix regulation of drug resistance in small-cell lung cancer.
SO - Clin Sci (Lond) 2002 Apr;102(4):417-24
AD - Centre for Inflammation Research, Rayne Laboratory, Medical School, University of Edinburgh, Teviot Place, Edinburgh EH8 9AG, Scotland, U.K. firstname.lastname@example.org
Tumour recurrence following chemotherapy remains a major obstacle to the cure of many cancers. This is exemplified by small-cell lung cancer (SCLC). Host-tumour interactions are central to tumour survival and proliferation. We hypothesized that a factor(s) within the local environment of SCLC cells could provide a survival signal or block a death signal, thereby accounting for the protection of SCLC cells from chemotherapy-induced apoptosis. Here we review recent work undertaken in our laboratory addressing this issue. We have shown that, in vivo, SCLC cells are surrounded by an extensive stroma of extracellular matrix (ECM) at both primary and metastatic sites which contains, among other proteins, fibronectin, laminin and collagen IV. Furthermore, adhesion of SCLC cells to fibronectin, laminin and collagen IV through beta1 integrins enhances tumorigenicity and confers resistance to apoptosis induced by standard chemotherapeutic agents, including etoposide, cis-platinum and adriamycin. Adhesion to ECM proteins stimulated protein tyrosine kinase (PTK) activity in both untreated and etoposide-treated cells. This effect could be completely blocked by a selective PTK inhibitor or by a function-blocking beta1 integrin antibody. PTK activation was found to block chemotherapy-induced activation of the death protease caspase-3 and, hence, apoptosis. Adhesion to ECM or treatment with a PTK inhibitor did not affect etoposide inhibition of topoisomerase II. Thus adhesion to ECM through beta1 integrins protects SCLC cells from chemotherapy-induced caspase-3 activation and apoptosis by activating PTK signalling downstream of DNA damage. Survival of tumour cells attached to ECM within this microenvironment could explain the local recurrence of SCLC and other tumours that is often seen clinically after chemotherapy.
UI - 12017298
AU - Vergote J; Moretti JL; Kouyoumdjian JC; Garnier-Suillerot A
TI - MRP1 modulation by PAK-104P: detection with technetium-99m-MIBI in cultured lung tumor cells.
SO - Anticancer Res 2002 Jan-Feb;22(1A):251-6
AD - Universite Paris Nord, Unite de Radiopharmacologie, UPRES 2360, UFR Sante Medecine Biologie Humaine, Bobigny, France.
BACKGROUND: Resistance mediated by the MultiDrug Resistance protein (P-glycoprotein and MRP1), results in energy-dependent efflux of drugs and 99mTc-MIBI from the cells. The goal of our investigation was to evaluate the capacity of PAK-104P to lower multidrug resistance by decreasing substrate efflux. MATERIALS AND METHODS: 99mTc-MIBI accumulation was quantified in the leukaemia cell line which expresses the P-glycoprotein (K562/R) or not (K562/S) and the small lung cancer cell line which expresses MRP1 (GLC4/R) or not (GLC4/S). Three experimental protocols were used: 1). cells were treated with increasing concentrations of PAK-104P; 2). the plasma membrane potential was lowered; 3). intracellular reduced glutathione (GSH) was depleted. RESULTS: Exposure of cells to 5 microM PAK-104P affected 99mTc-MIBI accumulation as follow: 1). no effect on K562 cell lines; 2). increased 8-fold in GLC4/R; 3). enhanced in GLC4 after GSH concentration and transmembrane potential reduction. CONCLUSION: Assessed by 99mTc-MIBI, PAK-104P modulated MRP1 activity by the decrease of intracellular GSH concentration.
UI - 12017323
AU - Gabius HJ; Andre S; Gunsenhauser I; Kaltner H; Kayser G; Kopitz J; Lahm
TI - H; Harms D; Szymas J; Kayser K Association of galectin-1- but not galectin-3-dependent parameters with proliferation activity in human neuroblastomas and small cell lung carcinomas.
SO - Anticancer Res 2002 Jan-Feb;22(1A):405-10
AD - Institut fur Physiologische Chemie, Tierarztliche Fakultat, Ludwig-Maximilians-Universitat, Munich, Germany.
BACKGROUND: Galectins, a family of animal lectins binding beta-galactosides, are involved in growth regulation of diverse cell types in vitro, even harboring the potential to act as biphasic modulators with cell type selectivity. Owing to this capacity they might affect tumor growth when expression is adapted adequately. MATERIALS AND METHODS: To determine galectin-1-/-3- related features in routinely-fixed sections of two tumor types with poor prognosis (neuroblastoma and small cell lung carcinoma), immuno- and lectin histochemistry with specific antibodies and labeled galectins was performed. RESULTS: In comparison to previously studied tissue culture models, galectin-3 was frequently present, documenting occurrence of discrepancies between tumor models and clinical material for this protein. Cytoplasmic staining with galectin-1 and its antibody coincides with the proliferative activity of positive tumor cells determined by the MIB-1 monoclonal antibody. No statistical correlation was seen for galectin-3. CONCLUSION: These results encourage further cell biological studies to assess a regulatory role of galectin-1 on cell growth in vitro as a model for interfering with tumor proliferation by modulating expression of this type of endogenous effector(s).
UI - 11911799
AU - Ruotsalainen TM; Mattson K
TI - Interferon trials in small cell lung cancer at one institution: a comparison of results obtained before and after initiation of systematic treatment trials using IFN-alpha in combination with other modalities.
SO - J Interferon Cytokine Res 2002 Feb;22(2):165-71
AD - Department of Oncology, Division of Respiratory Diseases, Helsinki University Central Hospital, Finland. Tarja.Routsalainen@hus.fi
Chemotherapy became the primary treatment for small cell lung cancer (SCLC) in the early 1970s. The standard drug combinations were first vincristine, adriamycin, and cyclophosphamide (VAC) and then, from the early 1980s, etoposide-platinum combinations. Despite a good initial objective response, however, patients usually suffer a rapid relapse. Treatment development has, therefore, focused on ways to overcome drug resistance, and on the addition of cytokines to the chemotherapeutic arsenal. Interferon (IFN) was one of the first cytokines found to have anticancer effects, and it was introduced into the combined modality regimens used to treat SCLC in the early 1980s in an attempt to overcome the problem of early relapse. The role of IFN was investigated with the aim of establishing how best to combine it with other treatments for SCLC. In this paper, we review the impact of IFN on the outcome for 714 SCLC patients who were treated in randomized IFN trials at one institution over a period of 20 years and IFN trials conducted at other institutions during the same period. The parameters we used at our institution to measure outcome tended to improve during the period when patients were being treated in our three randomized IFN trials, compared with the period when patients received only standard treatment in a nonclinical trial setting. However, the differences were not statistically significant. During this period, IFN was used as maintenance therapy, concomitantly with chemotherapy, and combined with other treatment modalities. Our experience is that IFN-alpha is most effective when administered as low-dose maintenance treatment. Other IFN trials published during the same period were small and heterogeneous. Results were inconsistent and added little new information, although it has been shown that high pretreatment levels of serum vascular endothelial growth factor (VEGF) predict a poor response to treatment and consequently a poor outcome. The recently confirmed antiangiogenic properties of IFN deserve to be investigated in studies of maintenance treatment, in combination with other biologic agents. Patient should be selected according to criteria based on pretreatment assessment of biologic markers, such as VEGF and basic fibroblast growth factor (bFGF). Our studies, all at one institution, pioneered the biologic treatment of solid tumors and developed a solid basis of knowledge for future studies of biologic agents in cancer treatment.
UI - 11976832
AU - Fukuoka K; Arioka H; Iwamoto Y; Fukumoto H; Kurokawa H; Ishida T;
TI - Tomonari A; Suzuki T; Usuda J; Kanzawa F; Kimura H; Saijo N; Nishio K Mechanism of vinorelbine-induced radiosensitization of human small cell lung cancer cells.
SO - Cancer Chemother Pharmacol 2002 May;49(5):385-90
AD - Pharmacology Division, National Cancer Center Research Institute, Tokyo, Japan.
Vinorelbine (Navelbine, KW-2307), a semisynthetic vinca alkaloid, is a potent inhibitor of mitotic microtubule polymerization. The aims of this study were to demonstrate vinorelbine-induced radiosensitization of human small cell lung cancer (SCLC) SBC-3 cells and to elucidate the mechanisms of radiosensitization. A clonogenic assay demonstrated that SBC-3 cells were sensitized to radiation by vinorelbine using different schedules combining exposure to both. The sensitizer enhancement ratios (SERs) at a cell survival level of 10% were 1.42+/-0.21 to 1.33+/-0.06, and 1.22+/-0.07 depending on schedule. Vinorelbine-induced radiosensitization did not depend on the schedule of the combined exposure. Flow cytometric analyses showed that the cells did not accumulate in the radiosensitive G(2)/M phase of the cell cycle after concurrent treatment with vinorelbine and radiation. The results of an alkaline filter elution assay demonstrated that in the presence of vinorelbine at 1 n M radiation-induced DNA strand breaks were not completely repaired at 24 h postradiation. We conclude that human SCLC SBC-3 cells are sensitized to radiation by vinorelbine and that a possible mechanisms of vinorelbine-induced radiosensitization may at least in part be associated with impairment of DNA repair following radiation-induced DNA damage.
UI - 12043222
AU - Sueyama H
TI - [Limited stage small cell lung cancer]
SO - Nippon Igaku Hoshasen Gakkai Zasshi 2002 Apr;62(5):194-7
AD - Division of Radiation Therapy, Niigata Prefectural Central Hospital.
Recent progress in the treatment of limited stage small cell lung cancer (LD-SCLC) is reviewed. SCLC represents 15-20% of all lung cancers. Combination chemotherapy is considered the treatment of choice because SCLC usually is widespread at diagnosis. The PE (CDDP + Etoposide) regimen and concurrent thoracic irradiation have yielded the best survival results in LD-SCLC. Although the timing of chemotherapy and thoracic radiation is still controversial, the early integration of chemotherapy and thoracic irradiation produces a small survival advantage over the late integration of chemoradiotherapy. Radiotherapy should be delivered to a smaller target volume based on CT planning, and twice-daily chest irradiation (accelerated hyperfractionation) is recommended because of improvement in local control and survival. Meta-analysis has shown that prophylactic cranial irradiation reduced the rate of brain metastases and increased 3-year survival by 5% in patients with SCLC in complete response.
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