Clinical Issues in the Management of Early Lung Cancer

Mulshine, James L.

doi:10.1158/1078-0432.ccr-05-9011

Cited by 9 publications

(5 citation statements)

References 39 publications

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“…However, despite its high sensitivity, specificity of CT in lung cancer detection is poor. 3 Therefore, serum biomarkers with high sensitivity and specificity for diagnosis of lung cancer are needed. However, current serum biomarkers for NSCLC such as carcino embryonic antigens (CEA) and squamous cell carcinoma antigen do not have sufficient sensitivity and specificity required for early detection of NSCLC.…”

Section: Uiccmentioning

confidence: 99%

WT1 IgG antibody for early detection of nonsmall cell lung cancer and as its prognostic factor

Oji

Kitamura

Kamino

et al. 2009

Intl Journal of Cancer

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There are urgent needs to develop methods for early detection of nonsmall cell lung cancer (NSCLC) because of its increasing incidence and poor prognosis. Here, we analyzed the production of IgG antibody (WT1 Ab) against WT1 (Wilms' tumor gene) protein that was overexpressed in the majority of NSCLC. Enzymelinked immuno-sorbent assay showed that WT1 Ab was produced in all of 91 NSCLC patients and 70 healthy individuals and that WT1 Ab titers were significantly higher in NSCLC patients compared with healthy individuals. When the cut-off level of WT1 Ab titers were fixed at mean 1 3SD of those in healthy individuals, 26.4% of NSCLC patients had WT1 Ab titers over the cut-off level, and positive rates of WT1 Ab at each clinical stage were 25.0, 30.8 and 38.4% in stage I, II and III NSCLC, respectively. When WT1 Ab was combined with CEA or CYFRA for detection of NSCLC, positive detection rates increased from 25.0 to 34.1 and 31.8%, respectively, in stage I and from 38.4 to 69.2 and 46.1%, respectively, in stage III, but not changed in stage II. Western blot analysis showed that dominant subclass of WT1 Ab was Th1-type IgG2. Interestingly, elevation of WT1 Ab titers was significantly associated with longer disease-free survival in patients with stages I-III NSCLC. These results showed that WT1 Ab could be a useful marker for early detection of NSCLC and its prognostic prediction. These results also suggested that WT1-specific immune responses played an important role in anti-cancer immunity in NSCLC. ' UICCKey words: lung cancer; WT1; humoral immune response; tumor marker; prognostic marker Lung cancer is the leading cause of cancer death in the world and nonsmall cell lung cancer (NSCLC) represents nearly 80% of the disease. 1 Because 75% of lung cancer patients are diagnosed at stages of metastatic spread when therapies are rarely curative, 2 early detection of localized lung cancer is the key to improve its clinical outcome.Although chest X-ray is routinely used as a screening tool, its limitation to detect localized lung cancer has been evident because of its insufficient sensitivity. 2 Recently, low-dose spiral computed tomography (CT) has been proposed as an early detection screening tool. However, despite its high sensitivity, specificity of CT in lung cancer detection is poor. 3 Therefore, serum biomarkers with high sensitivity and specificity for diagnosis of lung cancer are needed. However, current serum biomarkers for NSCLC such as carcino embryonic antigens (CEA) and squamous cell carcinoma antigen do not have sufficient sensitivity and specificity required for early detection of NSCLC. 4,5 It is now clear that malignant transformation occurs by changes in cellular gene expression with subsequent clonal proliferation. Altered gene expression in malignant cells may lead to the expression of aberrantly expressed proteins recognized by host immune system. If autoantibodies against these antigens are produced at early stage of NSCLC when quantity of the tumor antigens in the circulation is very small, these...

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Section: Uiccmentioning

confidence: 99%

WT1 IgG antibody for early detection of nonsmall cell lung cancer and as its prognostic factor

Oji

Kitamura

Kamino

et al. 2009

Intl Journal of Cancer

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“…Lung cancer is the leading cause of cancer deaths worldwide, with minimal changes in the 5‐year survival rate during the past decade 1–3. Lung cancers usually are classified into two main groups that account for about 95% of all cases.…”

Section: Introductionmentioning

confidence: 99%

“…Lung cancer is the leading cause of cancer deaths worldwide, with minimal changes in the 5-year survival rate during the past decade. [1][2][3] Lung cancers usually are classified into two main groups that account for about 95% of all cases. The two main types of lung cancer are characterized by the cell size of the tumor when viewed under the microscope.…”

Section: Introductionmentioning

confidence: 99%

Downregulation and growth inhibitory role of FHL1 in lung cancer

Niu

Liang

Guo

et al. 2011

Intl Journal of Cancer

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Four and a half Lin-11, Isl-1, Mac-3 (LIM) protein 1 (FHL1) has been linked to carcinogenesis. However, the role of FHL1 in lung cancer remains unclear and the detailed mechanism underlying its tumor suppressive role is poorly understood. The purpose of this study was to examine FHL1 expression in lung cancer patients and to investigate how it was associated with lung cancer cell growth. Immunoblotting and immunohistochemistry showed that FHL1 protein was downregulated in over 90% of 80 lung cancer patients. FHL1 expression was strongly correlated with tumor histological types (p < 10 24 ) and the differentiation of the tumor (p 5 0.002). FHL1 inhibited anchorage-dependent and -independent growth of human lung cancer cell lines. The inhibitory effects of FHL1 on lung cancer cell growth were associated with both the G1 and the G2/M cell cycle arrest concomitant with a marked inhibition of cyclin A, cyclin B1 and cyclin D as well as the induction of the cyclin dependent kinase inhibitors p21 (WAF1/CIP1) and p27 (Kip1). Direct intratumoral injection of an adenovirus expressing FHL1 dramatically suppressed the growth of A549 lung cancer cells in nude mice. Our data suggest that reduced expression of FHL1 may play an important role in the development and progression of lung cancer and that FHL1 may be a useful target for lung cancer gene therapy.

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“…As it is shown in Figure 5, this provides an excellent trade-off between adequate curve fit and physical limits of the motor, given that choosing smaller time intervals can result in amplitudes smaller than the motor step size around the maximum displacement point. Equation (2), which is an extension of equation (1) and the frequency calculation, is used to obtain a sinusoidal waveform to be translated into motion profile by using equations from the "reverse problem". Equation (3) represents the calculation used to determine the speed required for the motor to be able to closely match a desired motion profile.…”

Section: Motion-profile Calculation and Comparison With Three Tracking mentioning

confidence: 99%

Dynamic lung tumor phantom coupled with chest motion

Valle

Goryawala

McGoron

2008

Medical Imaging 2008: Visualization, Image-Guided Procedures, and Modeling

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Motion artifacts have always been a non-desired effect in the field of Medical Imaging. Thus new technologies are being investigated to ameliorate the damaging effects of image blurring caused by motion. The development of these new technologies requires the use of phantoms as a means of precise, repeatable and controllable source of motion for testing initial algorithms and prototypes. The objective of this project was to design a dynamic lung tumor phantom coupled with chest motion. The phantom consists of a pair of linear actuators. The complete design, excluding the actuators was built in house out of acrylic materials with low attenuation factors, making it ideal for PET studies. The linear actuator is a stepper motor coupled to a lead screw which translates rotational motion into linear displacement at a rate of 0.0254 mm/step. The system is driven by a PIC microcontroller that allows the user to select different tumor motion parameters, and is capable of performing 3D motion. The phantom is capable of providing lung tumor and chest position with an accuracy of 1.3 µm in the axis of motion, with a displacement of up to 52 mm and maximum velocity of 21.59 mm/second. The design has proven to be suitable for simulating lung tumor motion in PET studies, as well as testing motion tracking algorithms. However it can also be used in studies dealing with gated radiotherapy.

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Clinical Issues in the Management of Early Lung Cancer

Cited by 9 publications

References 39 publications

WT1 IgG antibody for early detection of nonsmall cell lung cancer and as its prognostic factor

WT1 IgG antibody for early detection of nonsmall cell lung cancer and as its prognostic factor

Downregulation and growth inhibitory role of FHL1 in lung cancer

Dynamic lung tumor phantom coupled with chest motion

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