UI - 12107105
AU - Yokoi S; Yasui K; Saito-Ohara F; Koshikawa K; Iizasa T; Fujisawa T;
Terasaki T; Horii A; Takahashi T; Hirohashi S; Inazawa J
A novel target gene, SKP2, within the 5p13 amplicon that is frequently
detected in small cell lung cancers.
SO - Am J Pathol 2002 Jul;161(1):207-16
AD - Department of Molecular Cytogenetics, Medical Research Institute, Tokyo
Medical and Dental University, Tokyo, Japan.
We investigated DNA copy-number aberrations in 22 cell lines derived
from small cell lung cancers (SCLCs) using comparative genomic
hybridization. A minimal common region at 5p13, within the 5p11-p13
amplicon that was most frequently involved, harbored the CDH6, PC4, and
SKP2 genes. These three genes showed amplification and consequent
overexpression in the SCLC cell lines. SKP2 positively regulates
progression of cell cycle by targeting several regulators, such as the
cell-cycle inhibitor p27(KIP1), for ubiquitin-mediated degradation. SKP2
was amplified in 7 (44%) of 16 primary SCLC tumors, and consequently
overexpressed in 10 (83%) of the 12 of those tumors we examined.
Expression levels of SKP2 protein were cell cycle-dependent in SCLC
cells as well as in normal cells, and were correlated with the DNA
copy-number of the gene. There was an inverse correlation between the
expression of SKP2 and p27(KIP1) proteins. Down-regulation of SKP2 using
an anti-sense oligonucleotide remarkably suppressed the growth of SCLC
cells. Our results indicate that SKP2 is likely to be a target of the
5p13 amplification and to play an important role in the growth of SCLC
UI - 12107114
AU - Yazawa T; Ito T; Kamma H; Suzuki T; Okudela K; Hayashi H; Horiguchi H;
Ogata T; Mitsui H; Ikeda M; Kitamura H
Complicated mechanisms of class II transactivator transcription
deficiency in small cell lung cancer and neuroblastoma.
SO - Am J Pathol 2002 Jul;161(1):291-300
AD - Department of Pathology, Yokohama City University School of Medicine,
Kanagawa, Japan. firstname.lastname@example.org
Small cell lung cancer (SCLC) and neuroblastoma (NB), the most
aggressive adult and infant neuroendocrine cancers, respectively, are
immunologically characterized by a severe reduction in major
histocompatibility complex (MHC) that is indispensable for anti-tumor
immunity. We had reported that the severe reduction of MHC in SCLC was
caused by a deficient interferon (IFN)-gamma-inducible expression of
class II transactivator (CIITA) that is known as a very important
transcription factor for IFN-gamma-inducible class II and class I MHC
expression (Yazawa T, Kamma H, Fujiwara M, Matsui M, Horiguchi H, Satoh
H, Fujimoto M, Yokohama K, Ogata T: Lack of class II transactivator
causes severe deficiency of HLA-DR expression in small cell lung cancer.
J Pathol 1999, 187:191-199). Here, we demonstrate that the reduction of
MHC in NB was also caused by a deficient IFN-gamma-inducible expression
of CIITA and that the deficiency in SCLC and NB was caused by similar
mechanisms. Human achaete-scute complex homologue (HASH)-1, L-myc, and
N-myc, which are specifically overexpressed in SCLC and NB, bound to the
E-box in CIITA promoter IV and reduced the transcriptional activity.
Anti-sense oligonucleotide experiments revealed that overexpressed L-myc
and N-myc lie upstream in the regulatory pathway of HASH-1 expression.
The expression of HASH-1 was also up-regulated by IFN-gamma. Our results
suggest that SCLC and NB have complicated mechanisms of
IFN-gamma-inducible CIITA transcription deficiency through the
overexpressed HASH-1, L-myc, and N-myc. These complicated mechanisms may
play an important role in the escape from anti-tumor immunity.
UI - 12118015
AU - Machtay M
The early rad catches the tumor?
SO - J Clin Oncol 2002 Jul 15;20(14):3045-7
UI - 12118018
AU - Takada M; Fukuoka M; Kawahara M; Sugiura T; Yokoyama A; Yokota S;
Nishiwaki Y; Watanabe K; Noda K; Tamura T; Fukuda H; Saijo N
Phase III study of concurrent versus sequential thoracic radiotherapy in
combination with cisplatin and etoposide for limited-stage small-cell
lung cancer: results of the Japan Clinical Oncology Group Study 9104.
SO - J Clin Oncol 2002 Jul 15;20(14):3054-60
AD - Osaka Prefectural Habikino Hospital, Osaka City General Medical Center,
Kinki National Hospital for Chest Disease, Osaka, Japan.
PURPOSE: To evaluate the optimal timing for thoracic radiotherapy (TRT)
in limited-stage small-cell lung cancer (LS-SCLC), the Lung Cancer Study
Group of the Japan Clinical Oncology Group conducted a phase III study
in which patients were randomized to sequential TRT or concurrent TRT.
PATIENTS AND METHODS: We treated 231 patients with LS-SCLC. TRT
consisted of 45 Gy over 3 weeks (1.5 Gy twice daily), and the patients
were randomly assigned to receive either sequential or concurrent TRT.
All patients received four cycles of cisplatin plus etoposide every 3
weeks (sequential arm) or 4 weeks (concurrent arm). TRT was begun on day
2 of the first cycle of chemotherapy in the concurrent arm and after the
fourth cycle in the sequential arm. RESULTS: Concurrent radiotherapy
yielded better survival than sequential radiotherapy (P =.097 by
log-rank test). The median survival time was 19.7 months in the
sequential arm versus 27.2 months in the concurrent arm. The 2-, 3-, and
5-year survival rates for patients who received sequential radiotherapy
were 35.1%, 20.2%, and 18.3%, respectively, as opposed to 54.4%, 29.8%
and 23.7%, respectively, for the patients who received concurrent
radiotherapy. Hematologic toxicity was more severe in the concurrent
arm. However, severe esophagitis was infrequent in both arms, occurring
in 9% of the patients in the concurrent arm and 4% in the sequential
arm. CONCLUSION: This study strongly suggests that cisplatin plus
etoposide and concurrent radiotherapy is more effective for the
treatment of LS-SCLC than cisplatin plus etoposide and sequential
UI - 12118020
AU - Papandreou CN; Daliani DD; Thall PF; Tu SM; Wang X; Reyes A; Troncoso P;
Results of a phase II study with doxorubicin, etoposide, and cisplatin
in patients with fully characterized small-cell carcinoma of the
SO - J Clin Oncol 2002 Jul 15;20(14):3072-80
AD - Department of Genitourinary Medical Oncology, The University of Texas
M.D. Anderson Cancer Center, Houston, TX 77030, USA.
PURPOSE: To determine the activity and toxicity of doxorubicin in
combination with cisplatin and etoposide in patients with small-cell
prostate carcinoma (SCPCa) and to characterize the clinicopathologic
features of SCPCa. PATIENTS AND METHODS: Patients with SCPCa (pure or
mixed), measurable disease, good organ function, and no prior treatment
with doxorubicin, etoposide, or cisplatin were treated every 4 weeks
with doxorubicin 50 mg/m(2) as a 24-hour intravenous (IV) infusion
followed by etoposide 120 mg/m(2)/d and cisplatin 25 mg/m(2)/d IV on
days 2 to 4. RESULTS: Thirty-eight patients (36 assessable for response)
were treated for a median of four cycles. Twenty-nine (81%) of 36
patients had prior hormonal therapy. Study patients had visceral
metastases, lytic bone disease, and relatively low serum
prostate-specific antigen (PSA). We observed 22 partial responses
(response rate, 61% in an intent-to-treat analysis); toxicity was severe
(grade 3 or 4 neutropenia 100%, thrombocytopenia 66%, mucositis 21%, and
infection 68%). Three patients died of toxicity. Median time to
progression and overall survival time were 5.8 months and 10.5 months,
respectively. Performance status, serum albumin, and number of organs
involved (but not PSA, carcinoembryonic antigen, or neuroendocrine
markers) were predictors of survival. CONCLUSION: SCPCa presents unique
clinicopathologic features. Addition of doxorubicin to the
etoposide/cisplatin regimen caused higher toxicity in this patient
population and failed to improve outcome. Given these results, we do not
recommend further development of this regimen for patients with SCPCa.
Improvement in therapy will come from understanding the biology of SCPCa
progression and integrating new targeted therapies into the treatment of
UI - 11948117
AU - Westerman BA; Neijenhuis S; Poutsma A; Steenbergen RD; Breuer RH; Egging
M; van Wijk IJ; Oudejans CB
Quantitative reverse transcription-polymerase chain reaction measurement
of HASH1 (ASCL1), a marker for small cell lung carcinomas with
SO - Clin Cancer Res 2002 Apr;8(4):1082-6
AD - Molecular Biology Laboratory, Department of Clinical Chemistry, VU
University Medical Center, 1081 HV Amsterdam, the Netherlands.
PURPOSE: The Human Achaete-Scute homologue 1 (HASH1, ASCL1), a
lineage-specific basic helix-loop-helix member of the achaete-scute
family, is essential for the generation of pulmonary neuroendocrine (NE)
cells during lung development. In small cell lung cancer (SCLC), the
most lethal form of lung cancer, the gene is highly expressed and the
expression of HASH1 correlates with NE features found in SCLCs. Here we
describe a highly sensitive reverse transcription-PCR method for
quantifying HASH1 mRNA in clinical samples, using real-time fluorescence
resonance energy transfer technology (LightCycler). EXPERIMENTAL DESIGN:
The HASH1-positive NE cell line NCI-H187 was compared with the non-NE
cell line NCI-N417 by quantitative reverse transcription-PCR. Signals
were normalized using the housekeeping gene PBGD, which is pseudogene
free. Subsequently, HASH1 expression in RNA isolated from biopsies from
SCLC patients (n = 4) was compared with biopsies from non-SCLC (NSCLC)
patients (n = 2) or normal bronchus (n = 2). RESULTS: The HASH1-positive
NE cell line NCI-H187 showed 50,000-fold higher normalized expression of
HASH1 than did the non-NE cell line NCI-N417, indicating that the method
is applicable over a wide dynamic range. Normalized average mRNA
expression levels in SCLC clinical samples were 1,000-fold higher than
in the NSCLC samples. Expression in normal bronchus was comparable to
the expression levels in the NSCLC. CONCLUSIONS: These results show that
marked and measurable differences exist between SCLCs and other lung
tissues (either NSCLC or normal bronchus). We show that the method is
applicable to small biopsy samples and can discriminate SCLC from NSCLC.
This method could contribute to diagnosis based on molecular profiling
UI - 12113068
AU - Anonymous
Genta initiates trials with Genasense.
SO - Expert Rev Anticancer Ther 2002 Feb;2(1):6
UI - 12113024
AU - Masuda N; Fukuoka M
Irinotecan in the treatment of small cell lung cancer.
SO - Expert Rev Anticancer Ther 2001 Aug;1(2):187-95
AD - Department of Respiratory Disease, Otemae Hospital, 1-5-34 Otemae,
Chuo-ku, Osaka, Osaka, 540-0008, Japan.
Combination chemotherapy is the cornerstone of treatment of small cell
lung cancer, leading to a meaningful survival benefit for these
patients. However, there have been no major advances in therapy in the
last decade. Therefore, more effective new treatments are necessary to
improve the outcome of therapy. Irinotecan is one of the new active
agents that provide hope for more effective therapies in the 21st
century. A Phase III trial carried out in Japan clearly demonstrated a
survival advantage of a combination of cisplatin and irinotecan over the
standard regimen of cisplatin and etoposide. This review outlines the
treatment results of irinotecan as a single agent as well as in
combination with other cytotoxic agents.
UI - 12113025
AU - Yip D; Karapetis C; Steer C
Management of small cell lung cancer.
SO - Expert Rev Anticancer Ther 2001 Aug;1(2):197-210
AD - Medical Oncology Unit, Canberra Hospital, Garran ACT 2605, Australia.
Small cell lung cancer is a tumor that has a very poor prognosis without
treatment. It is however, highly responsive to chemotherapy and
radiotherapy. Pretreatment clinical and laboratory parameters--in
addition to staging--can prognosticate outcome and help define the aim
of treatment. Different schedules of chemotherapy have been developed
and varied strategies, such as chemotherapy dose intensification have
been tried to improve outcomes. New agents, such as irinotecan,
gemcitabine and topotecan have also been tested. Clinical trials have
helped to define strategies of integrating thoracic radiotherapy and
prophylactic cranial radiotherapy into management of those patients with
limited disease to improve survival further. Despite good initial
responses to treatment, most patients eventually relapse. Maintenance
strategies with ongoing chemotherapy or novel agents, such as
interferon, matrix metalloproteinase inhibitors, thalidomide and
vaccines are discussed.
UI - 12113026
AU - Daniels GA; Adjei AA
Advances in systemic therapy of small cell cancer of the lung.
SO - Expert Rev Anticancer Ther 2001 Aug;1(2):211-21
AD - Division of Medical Oncology, Mayo Clinic, 200 First St. SW, Rochester,
MN 55905, USA.
Over the last 20 years, progress in the therapy of small cell lung
cancer has been painfully slow. Despite dramatic initial responses to
chemotherapy, most patients relapse quickly with an overall 5-year
survival of about 5%. Recent trials however offer some hope at changing
this picture. Combining standard regimens with newer agents has doubled
median survival in some cases. The use of novel targeted agents holds
the promise of significantly increasing the survival in this disease,
with manageable toxicity. This review outlines current treatment
strategies, summarizes recent clinical trials and offers a view of what
the next 5 years may hold for the treatment of small cell lung cancer.
UI - 12124327
AU - Zhang Y; Thant AA; Machida K; Ichigotani Y; Naito Y; Hiraiwa Y; Senga T;
Sohara Y; Matsuda S; Hamaguchi M
Hyaluronan-CD44s signaling regulates matrix metalloproteinase-2
secretion in a human lung carcinoma cell line QG90.
SO - Cancer Res 2002 Jul 15;62(14):3962-5
AD - Department of Molecular Pathogenesis, Nagoya University School of
Medicine, Nagoya 466-8550, Japan.
We investigated the production of matrix metalloproteinase (MMP) by
hyaluronan(HA) stimulation in a human cancer cell line, QG90, that
expresses a large amount of CD44s, a HA receptor. Treatment of QG90 with
HA strongly activated MMP-2 secretion in a time- and dose-dependent
manner. We found that expression of antisense CD44s in QG90 cells
substantially inhibited the HA-dependent secretion of MMP-2, whereas
overexpression of full-length CD44s augmented the HA-dependent secretion
of MMP-2. In addition, pretreatment of cells with the neutralizing
anti-CD44 antibody significantly inhibited both the HA-dependent MMP-2
secretion and the HA-dependent activation of mitogen-activated protein
kinase in a dose-dependent manner. Similarly, treatment of cells with a
Ras farnesyltransferase inhibitor, manumycin A, strongly inhibited the
HA-dependent MMP-2 secretion. Moreover, in vitro invasiveness of QG90
and its activation by HA were clearly suppressed by the expression of
antisense CD44s. In addition, treatment of cells with anti-CD44, a
mitogen-activated protein/extracellular signal-regulated kinase kinase 1
inhibitor, PD98059, or phosphatidylinositol 3'-kinase inhibitors,
wortmannin and LY294002, effectively blocked the HA-dependent activation
of the invasiveness. In contrast, overexpression of full-length CD44
substantially activated the invasiveness of QG90. Taken together,
HA-CD44s signaling plays a key role in the HA-dependent secretion of
MMP-2 and, hence, in the invasiveness of QG90 cells.
UI - 9662341
AU - Chevillard S; Radicella JP; Levalois C; Lebeau J; Poupon MF; Oudard S;
Dutrillaux B; Boiteux S
Mutations in OGG1, a gene involved in the repair of oxidative DNA
damage, are found in human lung and kidney tumours.
SO - Oncogene 1998 Jun 11;16(23):3083-6
AD - Departement de Radiobiologie et Radiopathologie, UMR217 CNRS-CEA
Radiobiologie Moleculaire et Cellulaire, Fontenay aux Roses, France.
The human OGG1 gene encodes a DNA glycosylase activity catalysing the
excision of the mutagenic lesion 7,8-dihydro-8-oxoguanine from
oxidatively damaged DNA. The OGG1 gene was localized to chromosome 3p25,
a region showing frequent loss of heterozygosity (LOH) in lung and
kidney tumours. In this study, we have analysed by RT-PCR the expression
of OGG1 in 25 small cell lung cancers, in 15 kidney carcinomas and the
15 normal kidney counterparts. The results show that OGG1 messenger RNA
can be detected in all tumours tested and that no significant difference
was observed in the level of expression between normal and tumoral
kidney tissues. Denaturing gradient gel electrophoresis (DGGE) was used
to screen this series of human tumours for alterations in the OGG1 cDNA.
The study revealed homozygous mutations in three tumours, two from lung
and one from kidney. Sequencing analysis of the mutants identified a
single base substitution in each of the three cases: two transversions
(GC to TA and TA to AT) and one transition (GC to AT). All three
substitutions cause an amino acid change in the hOgg1 protein. For the
mutant kidney tumour, the normal tissue counterpart shows a wild-type
profile. These results suggest a role for OGG1 mutations in the course
of the multistage process of carcinogenesis in lung or kidney.
UI - 12090170
AU - Sorenson S
[Irinotekan in spread small cell lung cancer. More studies are required
to change the practice]
SO - Lakartidningen 2002 May 23;99(21):2409
AD - Lungeavdelingen, Haukeland sykehus, Bergen, Norge.
UI - 10697572
AU - Bahadori HR; Rocha Lima CM; Green MR; Safa AR
Synergistic effect of gemcitabine and irinotecan (CPT-11) on breast and
small cell lung cancer cell lines.
SO - Anticancer Res 1999 Nov-Dec;19(6B):5423-8
AD - Department of Experimental Oncology, Medical University of South
Carolina, Charleston 29425, USA.
Gemcitabine (2'-2'-difluorodeoxycytidine, dFdC), an analog of
deoxycytidine, is an antineoplastic agent with clinical activity against
several types of cancer. Irinotecan (CPT-11), a topoisomerase I
inhibitor, is a drug with a broad spectrum of anticancer activity. Since
these drugs have different mechanisms of cytotoxicity and dose-limiting
toxicity profiles, preclinical combination studies were performed on the
MCF-7 breast cancer and the SCOG small cell lung cancer (SCLC) cell
lines. Both gemcitabine and CPT-11 as single agents were effective
growth inhibitors in these cell lines. Isobologram analysis revealed for
the first time that the combination of these drugs exerted synergy over
a wide range of concentrations in MCF-7 and SCOG cells. Moreover,
combination index (CI) analysis revealed that at low concentrations,
combinations of gemcitabine and CPT-11 show a synergistic growth
inhibitory effect on MCF-7 cells. However, in SCOG cells CI analysis
showed synergy at concentrations of gemcitabine and CPT-11 greater than
1 microM but antagonism at combination concentrations less than 1
microM. These preclinical cytotoxicity data provide an experimental
basis for conducting clinical trials using combinations of gemcitabine
and CPT-11, especially in patients with breast and lung cancers.
UI - 11098505
AU - Sherman CA; Rocha Lima CM; Turrisi AT
Limited small-cell lung cancer: a potentially curable disease.
SO - Oncology (Huntingt) 2000 Oct;14(10):1395-403; discussion 1403-4, 1409
AD - Division of Hematology/Oncology, Hollings Cancer Center, Medical
University of South Carolina, Charleston, USA.
Patients with limited-stage small-cell carcinoma of the lung are treated
with combined-modality therapy with the intent to cure. Standard therapy
consists of platinum-based combination chemotherapy, thoracic
irradiation, and for responders, prophylactic cranial irradiation.
Despite this aggressive approach, too few patients achieve 5-year
survival. In the past several years, new chemotherapeutic agents,
including the taxanes and the topoisomerase I inhibitors, have
demonstrated substantial activity against small-cell carcinoma. These
agents are now being incorporated into clinical trials for patients with
limited-stage disease. The best combination of these agents with
platinum-based regimens is yet to be determined, and data supporting
increased survival are awaited. Other studies are exploring thoracic
radiation issues. Questions remain regarding optimal timing, dose,
volume, and fractionation schemes. The most effective combination of
thoracic irradiation and the newer chemotherapy agents also remains to
be determined. The current approach to limited-stage small-cell
carcinoma is reviewed, ongoing trials are described, and future
directions are explored.
UI - 12153974
AU - Chin R Jr; McCain TW; Lucia MA; Cappellari JO; Adair NE; Lovato JF;
Dunagan DP; Brooks MA; Clark HP; Haponik EF
Transbronchial needle aspiration in diagnosing and staging lung cancer:
how many aspirates are needed?
SO - Am J Respir Crit Care Med 2002 Aug 1;166(3):377-81
AD - Section of Pulmonary and Critical Care Medicine, Department of Internal
Medicine, Wake Forest University School of Medicine, Medical Center
Boulevard, Winston-Salem, NC 27157-1054, USA. Rchin@wfubmc.edu
Transbronchial needle aspiration has emerged as a key technique for
sampling mediastinal adenopathy but variable yields are reported. To
determine the number of aspirates needed to optimize yield, we
prospectively studied transbronchial needle aspiration and the
sequential effect of each successive specimen on diagnostic yield in 79
patients with known or suspected lung carcinoma and mediastinal
adenopathy. A total of 451 aspirates were performed in 79 patients
(mean, 5.7 aspirates per patient; range, 2-13) with 45 cases (57%)
positive for malignancy. A cytologically positive transbronchial needle
aspiration occurred with the first aspirate in 42% of patients in whom
this procedure established mediastinal nodal involvement. All positive
results were achieved with seven or fewer aspirates. Similar yields were
obtained for small cell and non-small cell lung cancer after seven
aspirates. Rapid on-site specimen cytologic evaluation was used in 55 of
79 cases (70%), with a positive diagnosis obtained in 39 of 55 cases
(71%) with on-site evaluation compared with six of 24 cases (25%)
performed without on-site evaluation. The data suggest there is a
plateau in yield after seven transbronchial needle aspirates, which may
be sufficient to obtain an optimal yield in assessing patients with lung
cancer and mediastinal adenopathy.
The above citations and abstracts reflect those newly added to CANCERLIT for the month and topic listed in the title. The citations have been retrieved from CANCERLIT using a predefined search strategy of indexed subject terms. Although the search strategy has been refined as best as possible, citations may appear that are not directly related to the topic, and occasionally relevant references may be omitted.