Serum levels of sFas and sFasL during chemotherapy of lung cancer
The aim of this study was to assess the clinical usefulness of determination of soluble Fas (sFas) and soluble Fas Ligand (sFasL) during chemotherapy of lung cancer. Methods: The study included 80 patients (69 males; 11 females; mean age 64 years; 48 with non-small cell lung cancer-NSCLC, 32 with sm...
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Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
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irk-123456789-1385762018-06-20T03:10:09Z Serum levels of sFas and sFasL during chemotherapy of lung cancer Naumnik, W. Iżycki, T. Ossolińska, M. Chyczewska, E. Original contributions The aim of this study was to assess the clinical usefulness of determination of soluble Fas (sFas) and soluble Fas Ligand (sFasL) during chemotherapy of lung cancer. Methods: The study included 80 patients (69 males; 11 females; mean age 64 years; 48 with non-small cell lung cancer-NSCLC, 32 with small cell lung cancer-SCLC). The control group consisted of 15 healthy volunteers. The peripheral blood samples were taken before and after 4 cycles of chemotherapy. sFas and sFasL levels were assessed by Elisa method. Results: The serum sFas and sFasL levels observed at the end of the chemotherapy were higher in all patients with lung cancer compared to healthy volunteers. The levels of sFas and sFasL were higher after chemotherapy than before therapy. The levels of sFasL were significantly higher in SCLC patients than in NSCLC ones. There were no significant differences in serum sFasL levels in relation to clinical stage of lung cancer. After chemotherapy the levels of sFas were higher in patients with metastases. There were no significant differences in serum sFasL levels in relation to response to therapy. At the end of the therapy the serum levels of sFas were higher in Partial Response group than in Progressed patients. Before chemotherapy the levels of sFas were higher in Progressive Disease group than in No Change one. The levels of sFas observed after chemotherapy were higher in Partial Response group than in No Change one. Conclusion: Determination of serum sFas and sFasL levels can be useful in clinical practice, but their practical significance needs further studies. Цель работы —оценить клиническую целесообразность определения уровня растворимого Fas (sFas) и растворимого лиганда Fas (sFasL) в сыворотке кровибольных раком легкого при химиотерапии. Методы: обследовали 80 пациентов (69 мужчин и 11 женщин; средний возраст — 64 года; из них у 48 диагностирован немелкоклеточный рак легкого (НМКРЛ), у 32 — мелкоклеточный рак легкого (МКРЛ)). Контрольная группа состояла из 15 здоровых доноров. Образцы периферической крови брали до и после 4 курсов химиотерапии. Содержание sFas и sFasL ана лизировали иммунофер ментным методом. Результаты: уровни sFas и sFasLв сыворотке крови всех больных раком легк ого по окончании хими отерапии выше, чем таковые в контрольной группе и чем таковые до терапии. Уровень sFasL был значительно выше у больных МКРЛ, чем таковой у пациентов с НМКРЛ. Значительных различий в уровне sFasLв сыворотке крови в за висимости от клинической стадии заболевания не выявлено. По окончании химиотерапии уровень sFas выше у пациен тов с метастазами, а также в группе с частичным ответом на терапию, чем у больных с прогрессирующим заболеванием. До начала терапии уровень sFas был выше у больных с прогр ессирующим забо лева нием, чем у па циентов со стабильным состоянием , а по окончании терапии – у больных с частичным ответом по сравнению с группой больных со стабильным состоянием. Выводы: определение уровня sFas и sFasLв сыворотке крови может быть пр именено в клинической практике, но зна чимость та ких показателей необходимо определить в дальнейших исследованиях. 2007 Article Serum levels of sFas and sFasL during chemotherapy of lung cancer / W. Naumnik, T. Iżycki, M. Ossolińska, E. Chyczewska // Experimental Oncology. — 2007. — Т. 29, № 2. — С. 132–136. — Бібліогр.: 23 назв. — англ. 1812-9269 http://dspace.nbuv.gov.ua/handle/123456789/138576 en Experimental Oncology Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
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Original contributions Original contributions |
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Original contributions Original contributions Naumnik, W. Iżycki, T. Ossolińska, M. Chyczewska, E. Serum levels of sFas and sFasL during chemotherapy of lung cancer Experimental Oncology |
| description |
The aim of this study was to assess the clinical usefulness of determination of soluble Fas (sFas) and soluble Fas Ligand (sFasL) during chemotherapy of lung cancer. Methods: The study included 80 patients (69 males; 11 females; mean age 64 years; 48 with non-small cell lung cancer-NSCLC, 32 with small cell lung cancer-SCLC). The control group consisted of 15 healthy volunteers. The peripheral blood samples were taken before and after 4 cycles of chemotherapy. sFas and sFasL levels were assessed by Elisa method. Results: The serum sFas and sFasL levels observed at the end of the chemotherapy were higher in all patients with lung cancer compared to healthy volunteers. The levels of sFas and sFasL were higher after chemotherapy than before therapy. The levels of sFasL were significantly higher in SCLC patients than in NSCLC ones. There were no significant differences in serum sFasL levels in relation to clinical stage of lung cancer. After chemotherapy the levels of sFas were higher in patients with metastases. There were no significant differences in serum sFasL levels in relation to response to therapy. At the end of the therapy the serum levels of sFas were higher in Partial Response group than in Progressed patients. Before chemotherapy the levels of sFas were higher in Progressive Disease group than in No Change one. The levels of sFas observed after chemotherapy were higher in Partial Response group than in No Change one. Conclusion: Determination of serum sFas and sFasL levels can be useful in clinical practice, but their practical significance needs further studies. |
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Naumnik, W. Iżycki, T. Ossolińska, M. Chyczewska, E. |
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Naumnik, W. Iżycki, T. Ossolińska, M. Chyczewska, E. |
| author_sort |
Naumnik, W. |
| title |
Serum levels of sFas and sFasL during chemotherapy of lung cancer |
| title_short |
Serum levels of sFas and sFasL during chemotherapy of lung cancer |
| title_full |
Serum levels of sFas and sFasL during chemotherapy of lung cancer |
| title_fullStr |
Serum levels of sFas and sFasL during chemotherapy of lung cancer |
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Serum levels of sFas and sFasL during chemotherapy of lung cancer |
| title_sort |
serum levels of sfas and sfasl during chemotherapy of lung cancer |
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Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
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2007 |
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Original contributions |
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http://dspace.nbuv.gov.ua/handle/123456789/138576 |
| citation_txt |
Serum levels of sFas and sFasL during chemotherapy of lung cancer / W. Naumnik, T. Iżycki, M. Ossolińska, E. Chyczewska // Experimental Oncology. — 2007. — Т. 29, № 2. — С. 132–136. — Бібліогр.: 23 назв. — англ. |
| series |
Experimental Oncology |
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| first_indexed |
2025-07-10T06:05:49Z |
| last_indexed |
2025-07-10T06:05:49Z |
| _version_ |
1837238900580417536 |
| fulltext |
132 Experimental Oncology 29, 132–136, 2007 (June)
The Fas/FasL system is a major regulator of apop-
tosis [9]. Fas is a cell surface protein with a single
transmembrane domain, belonging to the nerve growth
factor receptor/TNF receptor family [15, 22]. FasL is
a type II membrane protein that belongs to the TNF
family [15, 22]. FasL is expressed in activated T cells
and lung cancer cells [15, 19, 22]. Fas is expressed on
the surface of cell membranes in a variety of normal
tissue cells and malignant cells including lung cancer
cells [19].
Fas-mediated apoptosis leads to the elimination of
activated T-cells following an immune response. i. e.,
killing a tumor [1]. Deregulation of Fas-mediated apop-
tosis is thought to play a role in the cancer progression,
lymph node involvement and metastasis [19].
It has been suggested that Fas/FasL systems
induce apoptosis of activated immune cells and that
the soluble isoforms of these proteins (sFas, sFasL)
also inhibit their functions [3]. Elevated serum levels
of sFas and sFasL have been observed in patients with
many kinds of cancer [6, 7, 21]. The sFas function has
not yet been fully elucidated, but there are several
findings suggesting the role of sFas in cancer progres-
sion [21]. sFas has been reported to play an important
role in the regulation of apoptosis as an inhibitor of
Fas-mediated apoptosis [21]. It has been revealed that
the Fas/FasL system is an important mechanism for
tumor escape from the immune system: expression of
FasL on tumor cell surfaces and emission of a soluble
form of FasL [15, 22]. Soluble Fas and FasL levels are
increased in peripheral blood of lung cancer patients
[19]. However, the clinical significance of circulating
sFas and sFasL has not been clarified, yet.
Materials and Methods
Patients. The study included 80 patients with car-
cinoma of the lung. They consisted of 69 males and
11 females (mean age of 64 years; ranged 29–78).
The tumors were histologically classified as adeno-
carcinoma in 8 cases, squamous cell carcinoma in
40 cases and small cell carcinoma in 32 cases. None
of the patients suffered from infectious, allergic, auto-
immune, or other systemic diseases such as diabetes
mellitus. The patients had not been previously treated
with chemotherapy. The control group for serum sFas
and sFasL concentrations comprised 15 healthy vo-
lunteers (12 males) with mean age of 61 years. There
were no significant differences in age and sex between
patients and controls. All patients had a history of
smoking. Informed written consent was obtained from
all healthy volunteers and all patients.
Methods. Before treatment, patients underwent
standard staging procedures consisting of physical
examination, serum chemistry examination, bron-
choscopy, chest CT scan and ultrasonography of the
abdomen. Further imaging techniques were used
when required clinically. The clinical stage of non
small cell lung cancer (NSCLC) was assigned accord-
ing to the International Union Against Cancer (TNM
classification). The classifications of small cell lung
cancer (SCLC) were made according to the Veterans
Administration Lung Cancer Study Group (LD-limited
disease; ED-extensive disease). After staging, the
patients were placed on cisplatin or platin-derived che-
motherapy, which was accompanied by radiotherapy
in the locally advanced forms. Standard criteria for
an objective response to therapy were used (WHO
guidelines). To exclude the possible interference
of chemotherapy, subsequent blood samples were
seruM levels of sfas and sfasl during cheMotherapy
of lung cancer
W. Naumnik*, T. Iżycki, M. Ossolińska, E. Chyczewska
Department of Pneumonology and Tuberculosis, Medical University of Bialystok, Poland
The aim of this study was to assess the clinical usefulness of determination of soluble Fas (sFas) and soluble Fas Ligand (sFasL) during
chemotherapy of lung cancer. Methods: The study included 80 patients (69 males; 11 females; mean age 64 years; 48 with non-small
cell lung cancer-NSCLC, 32 with small cell lung cancer-SCLC). The control group consisted of 15 healthy volunteers. The peripheral
blood samples were taken before and after 4 cycles of chemotherapy. sFas and sFasL levels were assessed by Elisa method. Results: The
serum sFas and sFasL levels observed at the end of the chemotherapy were higher in all patients with lung cancer compared to healthy
volunteers. The levels of sFas and sFasL were higher after chemotherapy than before therapy. The levels of sFasL were significantly
higher in SCLC patients than in NSCLC ones. There were no significant differences in serum sFasL levels in relation to clinical stage
of lung cancer. After chemotherapy the levels of sFas were higher in patients with metastases. There were no significant differences in
serum sFasL levels in relation to response to therapy. At the end of the therapy the serum levels of sFas were higher in Partial Response
group than in Progressed patients. Before chemotherapy the levels of sFas were higher in Progressive Disease group than in No Change
one. The levels of sFas observed after chemotherapy were higher in Partial Response group than in No Change one. Conclusion: De-
termination of serum sFas and sFasL levels can be useful in clinical practice, but their practical significance needs further studies.
Key Words: soluble Fas, soluble Fas ligand, small cell lung cancer, non-small cell lung cancer, chemotherapy.
Received: January 7, 2007.
*Correspondence: �e���a�: ���� ���� 7�2�����e���a�: ���� ���� 7�2����
E-mai�: naumw@post.p�
Abbreviations used: NSCLC — non sma�� ce�� �ung cancer; sFasL —
so�ub�e Fas �igand; SCLC — sma�� ce�� �ung cancer.
Exp Oncol 2007
29, 2, 132–136
Experimental Oncology 29, 132–136, 2007 (June) 13329, 132–136, 2007 (June) 133June) 133) 133 133
obtained at least 28 days after the last administra-
tion of cytotoxic drugs. To determine sFas and sFasL
serum concentrations, venous blood samples were
collected from each patient before and after IV cycles
of chemotherapy (some of the patients underwent
later radiotherapy). Serum samples were obtained
by centrifugation and stored at –80 °C until assayed.
Serum sFas and sFasL concentrations were measured
by a single laboratory with an enzyme immunoassay
(Human sFas Immunoasay — R & D systems; human
sFas Ligand ELISA — Bender MedSystems) according
to the manufacturer’s instructions.
Statistical analysis. Data were presented as
mean ± 1 SD or median (range), depending on their
normal or skewed distribution provided by Shapiro-
Wilk’s W-test. Data for sFas and sFasL concentra-
tions in the serum samples from healthy subjects
and from patients with lung cancer were analyzed
using Student’s t-test for independent samples. Dif-
ferences among groups of patients before and after
chemotherapy were determined using Student’s t-test
for dependent samples. In the case of skewed distri-
bution, the data were analyzed using Wilcoxon’s-test
and Mann-Whitney’s U-test for unpaired data. The
correlation between the parameters was calculated
by the Spearman’s and Pearson’s rank tests.
All p values were two-tailed, and the values less
than 0.05 were considered statistically significant.
Computations were performed using Statistica 6.0 for
Windows (StatSoft Inc., Tulsa, OK., USA).
results
Serum sFas and sFasL levels in healthy volun-
teers and patients with lung cancer. As shown in
Table 1, the serum sFas and sFasL levels observed at
the end of the chemotherapy, were significantly higher
in 80 patients with lung cancer, compared to 15 healthy
volunteers (p = 0.017; p = 0.037). The levels of sFas
and sFasL were higher after chemotherapy than before
chemotherapy (p = 0.00001; p = 0.023).
The levels of sFasL were higher in SCLC patients
than in NSCLC ones. There were no significant diffe-
rences in serum sFas with regard to a histologic type
(Table 1).
There were no significant differences in serum
sFasL levels in relation to clinical stage of NSCLC and
SCLC (Table 1).
Serum sFas and sFasL levels in relation to re-
sponse to therapy. There were no significant differ-
ences in serum sFasL levels in relation to response to
therapy (Table 2). At the end of the therapy the serum
levels of sFas were higher in Partial Response group
than in Progressed patients (p = 0.032) (Fig. 1). Before
chemotherapy the levels of sFas were higher in Progres-
sive Disease group than in No Change group (p = 0.02)
(Table 2). In NSCLC group, the levels of sFas observed
after chemotherapy were higher in Partial Response
group than in No Change group (p = 0.03) (Table 2).
After chemotherapy the levels of sFas were higher in
patients with metastases (p = 0.02) (Fig. 2).
Table 1. Serum sFas and sFasL �eve�s in �ung cancer patients and contro�s
Disease
stage
Be�ore chemotherapy
(p-va�ue vs contro�s)
A�ter chemotherapy
(p-va�ue vs contro�s)
Contro�s
(n = ���)
Lung carcino-
ma patients
(n = ��0)
sFas
sFasL
���.�� ± 2��*
���7.2 (�66–��0�)#
�22�.� ± �0�**
p = 0.0�7
�02.� (���–���0)##
p = 0.0�7
227.� ± �2
�26.7 (����–��70)
NSCLC
(n = ���)
sFas
sFasL
�007.�� ± 2�6
���.6 (�66–6��0)�
�2���.0 ± ����
�6�.�� (���–����)�
III B (n = 2��)
sFas
sFasL
�66.2 ± 2����
�6�.�� (��7–����)
����2.7 ± �����
�72.�� (���–����)
IV (n = 2�)
sFas
sFasL
�07��.7 ± ����
���.6 (�66–6��0)
�����.�� ± ��2
����.� (�66–�0�)
SCLC (n = �2)
sFas
sFasL
�6��,0 ± �06
�67.� (26�–��0�)2
����.� ± ���
���2.� (�66–���0)�
LD (n = ���)
sFas
sFasL
��0.� ± �0��
�6�.7 (27��–��0�)
�2���.6 ± ��2
���2.� (2����–���0)
ED (n = �7)
sFas
sFasL
�0�0.�� ± �07
�67.� (26�–�0�)
��70.�� ± �2��
�7�.� (�66–���)
Notes: sFas – so�ub�e Fas (pg�m�); sFasL – so�ub�e Fas Ligand (pg�m�);
* vs ** p = 0.0000� ; # vs ## p = 0.02�; � vs 2 p = 0.0�; � vs � p = 0.0�.
fig. 1. The serum levels of sFas after chemotherapy of lung
cancer in respect to response to therapy
Table 2. Va�ues o� sFas and sFasL be�ore and a�ter chemotherapy o� �ung cancer patients
PR (n = ���) NC (n = �7 ) PD (n = �6)
be�ore chemotherapy a�ter chemotherapy be�ore chemotherapy a�ter chemotherapy be�ore chemotherapy a�ter chemotherapy
NSCLC (n = ���)
sFas
sFasL
�000.� ± 272
���.6 (2���–����)
�����.0 ± �76*
�6�.�� (2����–��7)
�0�.2 ± ���*#
���7.2 (�66–6��0)
�����.�� ± �20**
�6�.�� (���–����)
��20.�� ± 27��##
����.2 (��7–���2)
���0.� ± 2���#
�6��.6 (2�7–����)
PR (n = �7) NC (n = �) PD (n = �2)
be�ore chemotherapy a�ter chemotherapy be�ore chemotherapy a�ter chemotherapy be�ore chemotherapy a�ter chemotherapy
SCLC (n = �2)
sFas
sFasL
�0�2.6 ± 272
�7�.� (26�–��0�)
�20�.� ± ���
���2.� (�66–�����)
�����.0; ��7��.�; ����.�
��2.2; ���2.�; ���2.�
��77.�; �����.7; �2��0.2
����.��; �67.�; ���2.��
��0�.�� ± ��2
����.�� (2�2–��7)
���0.6 ± ��7
���2.� (20�–���0)
Notes: sFas — so�ub�e Fas (pg�m�); sFasL — so�ub�e Fas Ligand (pg�m�); PR — partia� response; NC — no change; PD — progressive disease vs ** p = 0.0�;
* vs # p = 0.00��; *# vs ## p = 0.02.
134 Experimental Oncology 29, 132–136, 2007 (June)
fig. 2. The serum levels of sFas after chemotherapy of lung
cancer in Mo and M1 patients
discussion
Many studies have revealed that the Fas/FasL sys-
tem is an important mechanism for tumor escape from
the immune system: expression of FasL on tumor cell
surfaces and release of a soluble form of FasL [15, 22].
The high serum sFas concentration was proved in pa-
tients with cancers: hepatocellular carcinoma [6], renal
cell carcinoma [7] and breast cancer [21], which is in
accordance with the results of our study. We proved
that sFas concentration observed after chemotherapy
was higher in the serum of patients with lung cancer
than in healthy individuals. Higher concentrations
were also observed in lung cancer patients before
chemotherapy in comparison with healthy individuals,
though the differences were not statistically significant.
Similarly, Yoshimura et al. [23] and Shimizu et al. [19]
showed higher serum sFas concentrations in patients
with lung cancer compared to healthy individuals.
The origin of sFas in the serum remains unclear,
though there are three possible theories. sFas may be
derived from the tumor itself [18], or from peripheral
blood lymphocytes [8]. The third theory indicates that
the surrounding stromal tissue may produce sFas in
response to the tumor or immune activation [12]. sFas
is formed due to cleavage of the external part of extra-
cellular Fas and acts as a FasL inhibitor to bind Fas and
prevent Fas- mediated apoptosis. Nonomura et al. [16]
claimed that immune cells, essentially lymphocytes,
NK and T cells were the most important sources of
sFas in response to a developing tumor. However, the
results of our study suggest that cancerous cells are
the main source of sFas in the serum of patients with
lung cancer.
The enhanced serum concentration if an apoptosis
inhibitor (sFas) in patients with lung cancer reflects an
intense inhibition of cancerous cells apoptosis, which
promotes the development of the tumor. Micheau
et. al. [11] proved that cytostatics caused the increase
in serum sFas, whereas Shimizu et al. [19] showed
that sFas increased in the serum together with clinical
staging of cancer. Our study confirmed this finding —
sFas concentration was higher after chemotherapy
than before treatment, where as patients with distant
NSCLC metastases had higher sFas concentration
than patients without metastases.
We found that patients with NSCLC that showed
partial remission (PR) after chemotherapy, had higher
sFas concentration than patients with No Change (NC)
or Partial Response (PR). Cytostatics destroying can-
cerous cells may release sFas from these cells.
The results of our study are in agreement with
Kondera-Anasz’s et al. study [9] based on the group
of women with cervical cancer, and with Midis’s et al.
[12] findings based on nonhematopoietic human ma-
lignancy. The high serum sFas concentration found
in patients with metastases, may cause resistance
to treatment by inhibiting Fas-mediated apoptosis in
cancer cells [21]. Various observations of different
cancers may indicate that the mechanism of sFas
induction might differ depending on tumor type.
We did not prove that determination of sFas
concentration might be useful in diagnostics of lung
cancer Shimizu et al. [19] indicated such a possibility,
however, it requires further studies performed in more
numerous groups of patients.
In addition to Fas, FasL also exists in a soluble form
released from cell surfaces after cleavage by metal-
loproteinases [20]. FasL is expressed in activated T
cells and lung cancer cells [2]. An increase in serum
sFasL concentration was proved in patients with vari-
ous cancers [4, 17]. It has been proposed that cancer
cells expressing FasL have an advantage to evade
human immune surveillance by inducing apoptosis
in infiltrating lymphocytes expressing Fas [1]. sFasL,
cleft by metalloproteinases, protects FasL of tumor
cells against their recognition by Fas of T lymphocytes
(imitation of tumor cells). Shimuzu et al. [19] sug-
gested that soluble FasL played an important role in
tumor genesis and anticancer cytotoxic activity, similar
to soluble Fas.
The behavior of serum sFasL in cancer patients is
controversial. Enjoji et al. [3] showed that the levels
of sFasL were not detectable in biliary carcinoma pa-
tients. In Murakami’s et al. [14] study, the serum levelsIn Murakami’s et al. [14] study, the serum levels14] study, the serum levels
of sFasL were significantly lower in bile duct carcinoma
patients than in healthy individuals. Conversely, Ichi-
kura et al. [5] showed that the levels of sFasL were
higher in gastric carcinoma patients than in healthy
volunteers. Our results are in agreement with obser-
vations made by Ichikura et al. [5]. We showed that
the levels of sFasL in lung cancer patients (observed
after chemotherapy) were higher than in controls. The
same observations were made by Mouawad et al. [13]
in melanoma patients. In this study, the levels of sFas
and sFasL in patients were higher in patients than in
healthy donors. We did not observed significant diffe-
rences in serum sFasL level in relation to clinical stage
of the tumor. The same observations were made by
Melzani et al. [10] in patients with melanoma.
When SCLC is diagnosed, cancer cells are already
present in the whole organism, transported via blood
vessels (independently of classification by imagining
tests as ED or LD). Thus, it is justified that we found
the higher sFasL concentration in patients with SCLC
than NSCLC.
Experimental Oncology 29, 132–136, 2007 (June) 13529, 132–136, 2007 (June) 135June) 135) 135 135
Summing up, sFas and sFasL play a significant role
in patients with lung cancer. Determination of serum
sFas and sFasL concentrations may be helpful to as-
sess clinical staging and effects of chemotherapy.
However, it requires further studies.
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136 Experimental Oncology 29, 132–136, 2007 (June)
Уровень� sfas ���� sfasl в ��воро��е �ров�� �о�ь�н���в ��воро��е �ров�� �о�ь�н��� ��воро��е �ров�� �о�ь�н�����воро��е �ров�� �о�ь�н��� �ров�� �о�ь�н����ров�� �о�ь�н��� �о�ь�н����о�ь�н���
ра�ом� �е��о�о на �оне ����м���о�ера����� �е��о�о на �оне ����м���о�ера�����на �оне ����м���о�ера����� �оне ����м���о�ера������оне ����м���о�ера����� ����м���о�ера���������м���о�ера�����
Цель� работы� �� о����т�� ������������ �����ообра��о�т�� о�р��������� �ро���� ра�т�ор��о�о Fas (sFas) � ра�т�ор��о�о �� о����т�� ������������ �����ообра��о�т�� о�р��������� �ро���� ра�т�ор��о�о Fas (sFas) � ра�т�ор��о�о�� о����т�� ������������ �����ообра��о�т�� о�р��������� �ро���� ра�т�ор��о�о Fas (sFas) � ра�т�ор��о�о о����т�� ������������ �����ообра��о�т�� о�р��������� �ро���� ра�т�ор��о�о Fas (sFas) � ра�т�ор��о�оо����т�� ������������ �����ообра��о�т�� о�р��������� �ро���� ра�т�ор��о�о Fas (sFas) � ра�т�ор��о�о ������������ �����ообра��о�т�� о�р��������� �ро���� ра�т�ор��о�о Fas (sFas) � ра�т�ор��о�о������������ �����ообра��о�т�� о�р��������� �ро���� ра�т�ор��о�о Fas (sFas) � ра�т�ор��о�о �����ообра��о�т�� о�р��������� �ро���� ра�т�ор��о�о Fas (sFas) � ра�т�ор��о�о�����ообра��о�т�� о�р��������� �ро���� ра�т�ор��о�о Fas (sFas) � ра�т�ор��о�о о�р��������� �ро���� ра�т�ор��о�о Fas (sFas) � ра�т�ор��о�оо�р��������� �ро���� ра�т�ор��о�о Fas (sFas) � ра�т�ор��о�о �ро���� ра�т�ор��о�о Fas (sFas) � ра�т�ор��о�о�ро���� ра�т�ор��о�о Fas (sFas) � ра�т�ор��о�о ра�т�ор��о�о Fas (sFas) � ра�т�ор��о�ора�т�ор��о�о Fas (sFas) � ра�т�ор��о�о Fas (sFas) � ра�т�ор��о�о� ра�т�ор��о�о ра�т�ор��о�ора�т�ор��о�о
���а��а Fas (sFasL) � �ы��орот�� �ро�� бо����ы��� ра�о� ����о�о �р� �����от�ра���. Fas (sFasL) � �ы��орот�� �ро�� бо����ы��� ра�о� ����о�о �р� �����от�ра���.� �ы��орот�� �ро�� бо����ы��� ра�о� ����о�о �р� �����от�ра���. �ы��орот�� �ро�� бо����ы��� ра�о� ����о�о �р� �����от�ра���.�ы��орот�� �ро�� бо����ы��� ра�о� ����о�о �р� �����от�ра���. �ро�� бо����ы��� ра�о� ����о�о �р� �����от�ра���.�ро�� бо����ы��� ра�о� ����о�о �р� �����от�ра���. бо����ы��� ра�о� ����о�о �р� �����от�ра���.бо����ы��� ра�о� ����о�о �р� �����от�ра���. ра�о� ����о�о �р� �����от�ра���.ра�о� ����о�о �р� �����от�ра���. ����о�о �р� �����от�ра���.����о�о �р� �����от�ра���. �р� �����от�ра���.�р� �����от�ра���. �����от�ра���.�����от�ра���.. Методы: об����о�а�� 80 �а����то�
(69 ��ж��� � 11 ж��щ��; �р����й �о�ра�т �� 64 �о�а; �� ���� � 48 ��а��о�т�ро�а� ������о���то��ы�й ра� ����о�о (НМКРЛ),
� 32 �� ����о���то��ы�й ра� ����о�о (МКРЛ)). Ко�тро����а�� �р���а �о�то���а �� 15 ��оро�ы��� �о�оро�. Обра��ы� ��р�ф�-
р�����ой �ро�� бра�� �о � �о��� 4 ��р�о� �����от�ра���. Со��ржа��� sFas � sFasL а�а����ро�а�� �����оф�р���т�ы��sFas � sFasL а�а����ро�а�� �����оф�р���т�ы�� � sFasL а�а����ро�а�� �����оф�р���т�ы��sFasL а�а����ро�а�� �����оф�р���т�ы�� а�а����ро�а�� �����оф�р���т�ы��
��то�о�. Резуль�таты: �ро��� sFas � sFasL � �ы��орот�� �ро�� ����� бо����ы��� ра�о� ����о�о �о о�о��а��� �����от�ра���sFas � sFasL � �ы��орот�� �ро�� ����� бо����ы��� ра�о� ����о�о �о о�о��а��� �����от�ра��� � sFasL � �ы��орот�� �ро�� ����� бо����ы��� ра�о� ����о�о �о о�о��а��� �����от�ра���sFasL � �ы��орот�� �ро�� ����� бо����ы��� ра�о� ����о�о �о о�о��а��� �����от�ра��� � �ы��орот�� �ро�� ����� бо����ы��� ра�о� ����о�о �о о�о��а��� �����от�ра���
�ы�ш�, ��� та�о�ы�� � �о�тро����ой �р���� � ��� та�о�ы�� �о т�ра���. Уро����� sFasL бы�� ��а��т�����о �ы�ш� � бо����ы���sFasL бы�� ��а��т�����о �ы�ш� � бо����ы��� бы�� ��а��т�����о �ы�ш� � бо����ы���
МКРЛ, ��� та�о�ой � �а����то� � НМКРЛ. З�а��т�����ы��� ра�����й � �ро��� sFasL � �ы��орот�� �ро�� � �а�����о�т� отsFasL � �ы��орот�� �ро�� � �а�����о�т� от � �ы��орот�� �ро�� � �а�����о�т� от
���������ой �та��� �або���а���� �� �ы�������о. По о�о��а��� �����от�ра��� �ро����� sFas �ы�ш� � �а����то� � ��та�та�а��,sFas �ы�ш� � �а����то� � ��та�та�а��, �ы�ш� � �а����то� � ��та�та�а��,
а та�ж� � �р���� � �а�т���ы�� от��то� �а т�ра����, ��� � бо����ы��� � �ро�р����р���щ�� �або���а����. До �а�а�а т�ра���
�ро����� sFas бы�� �ы�ш� � бо����ы��� � �ро�р����р���щ�� �або���а����, ��� � �а����то� �о �таб�����ы�� �о�то������, а �оsFas бы�� �ы�ш� � бо����ы��� � �ро�р����р���щ�� �або���а����, ��� � �а����то� �о �таб�����ы�� �о�то������, а �о бы�� �ы�ш� � бо����ы��� � �ро�р����р���щ�� �або���а����, ��� � �а����то� �о �таб�����ы�� �о�то������, а �о
о�о��а��� т�ра��� – � бо����ы��� � �а�т���ы�� от��то� �о �ра������� � �р���ой бо����ы��� �о �таб�����ы�� �о�то������. Выводы:
о�р�������� �ро���� sFas � sFasL � �ы��орот�� �ро�� �ож�т бы�т�� �р������о � ���������ой �ра�т���, �о ��а���о�т�� та����sFas � sFasL � �ы��орот�� �ро�� �ож�т бы�т�� �р������о � ���������ой �ра�т���, �о ��а���о�т�� та���� � sFasL � �ы��орот�� �ро�� �ож�т бы�т�� �р������о � ���������ой �ра�т���, �о ��а���о�т�� та����sFasL � �ы��орот�� �ро�� �ож�т бы�т�� �р������о � ���������ой �ра�т���, �о ��а���о�т�� та���� � �ы��орот�� �ро�� �ож�т бы�т�� �р������о � ���������ой �ра�т���, �о ��а���о�т�� та����
�о�а�ат���й ��об��о���о о�р�����т�� � �а�����йш��� ������о�а������.
Ключевые слова: ра�т�ор��ы�й Fas, ра�т�ор��ы�й ���а�� Fas, ����о���то��ы�й ра� ����о�о, ������о���то��ы�й ра� ����о�о,Fas, ра�т�ор��ы�й ���а�� Fas, ����о���то��ы�й ра� ����о�о, ������о���то��ы�й ра� ����о�о,, ра�т�ор��ы�й ���а�� Fas, ����о���то��ы�й ра� ����о�о, ������о���то��ы�й ра� ����о�о,Fas, ����о���то��ы�й ра� ����о�о, ������о���то��ы�й ра� ����о�о,, ����о���то��ы�й ра� ����о�о, ������о���то��ы�й ра� ����о�о,
�����от�ра����.
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