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NCI CANCERLIT® Search: Small Cell Lung Cancer - February 2002
National Cancer Institute®
Ultima Vez Modificado: 1 de febrero del 2002
Table of Contents
1
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.
2
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.
3
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.
fkaye@helix.nih.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.
4
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. pprakash_mail@yahoo.com
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.
5
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. yangy@upstate.edu
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.
6
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. dchhieng@path.uab.edu
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.
7
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.
8
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.
9
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.
10
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.
11
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.
12
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.
13
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.
14
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.
15
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.
16
UI - 11583181
AU - ESMO.
TI -
ESMO Minimum Clinical Recommendations for diagnosis, treatment and
follow-up of small-cell lung cancer (SCLC).
SO - Ann Oncol 2001 Aug;12(8):1051-2
17
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.
18
UI - 11826505
AU - Bychkov MB; Orel NF; Naskhletashvili DR
TI -
[Present-day possibilities of the treatment of small cell cancer of the
lung]
SO - Vopr Onkol 2001;47(6):757-61
19
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.
20
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.
21
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.
22
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. hecogoff@otenet.gr
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.
23
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.
24
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.
25
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. mil@cn.stam.dk
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.
26
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. kaki1967@xa2.so-net.ne.jp
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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