Società Italiana di Cancerologia
Associazione Italiana di Radioterapia Oncologica
Associazione Italiana di Oncologia Medica
Società Italiana di Chirurgia Oncologica
Volume 95
Numero 6
novembre-dicembre 2009
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titolo -
split_articolo,controlla_titolo
-
art_titolo
Enhancing apoptosis and overcoming resistance of gemcitabine in pancreatic cancer with bortezomib: a role of death-associated protein kinase-related apoptosis-inducing protein kinase 1
autori -
vau_aut_id
Qingqu Guo, Ying Chen, Yulian Wu
affiliazione_autori -
ignora
Department of Surgery, Second Affiliated Hospital, College of Medicine, Zhejiang University, Cancer Institute of Zhejiang University, P.R. China
parolechiave -
lingua
-
vke_key_id
Key words:
apoptosis, bortezomib, DRAK1, pancreatic cancer.
riassunto -
art_riassunto
abstract
Aims and background.
To investigate the role of the apoptosis gene, DAP (death-associated protein) kinase-related apoptosis-inducing protein kinase 1 (DRAK1), which is involved in enhancing cell sensitivity and overcoming cell
resistance to gemcitabine in pancreatic cancer cells by the proteasome inhibitor bortezomib.
Methods.
Cultured human pancreatic cancer gemcitabine-sensitive cell lines (bxpc-3) and gemcitabine-resistant (panc-1) cell lines were divided into four groups: control, treatment with bortezomib, treatment with gemcitabine, and the two-drug combination. Expression of DRAK1 genes in each group was detected by using reverse transcription-polymerase chain reaction and western blot. Apoptosis in the pancreatic cancer cell lines was measured by flow cytometry.
Results.
We found that the effects of growth inhibition and apoptosis of gemcitabine on both pancreatic cancer cell lines were enhanced by bortezomib. Treatment of panc-1 and bxpc-3 cells with bortezomib (100 nM) and gemcitabine (50 µg/ml and 0.05 µg/ml, respectively) induced an increase in the levels of DRAK1 mRNA compared with the control and single-agent treatment. Furthermore, immunblotting analysis in panc-1 but not bxpc-3 cells showed similar changes in the expression of DRAK1 protein produced by combination therapy.
Conclusions
. Our results demonstrated that bortezomib enhanced cell sensitivity and overcame cell resistance to gemcitabine in pancreatic cancer cells, which may be attributed to DRAK1 induced by bortezomib and the combination with gemcitabine.
testo -
art_testo
Introduction
Pancreatic cancer is one of the most devastating cancers. It is responsible for 5 to 6% of all cancer-related deaths. It remains a disease with a poor prognosis, with a 5-year survival rate of <4%, which has remained unchanged in the last decades
1
. Systemic chemotherapy may increase survival and improve quality of life for patients with resected and locally advanced pancreatic cancer. Currently, gemcitabine (2’,2’-difluorodeoxycitidine), a novel pyrimidine nucleoside analogue, has become the standard chemotherapeutic drug for pancreatic cancer. However, gemcitabine treatment alone is not very effective and is associated with multiple adverse events and drug resistance
2,3
. In view of the problem of gemcitabine drug resistance, it is important to develop new agents and innovative approaches to treat pancreatic cancer.
In eukaryotic cells, the ubiquitin-proteasome is essential for the disposal of damaged or unwanted proteins. As a large multicatalytic protease complex, the proteasome is responsible for most non-lysosomal intracellular protein degradation
4
. The proteasome inhibitor bortezomib (also known as Velcade [Mellimnnium Pharmaceuticals] or PS-341) represents a new type of chemotherapeutic drug that has been shown to induce apoptosis independently or synergistically with conventional cancer therapy in both solid and hematological tumors. Bortezomib is a dipeptidyl boronic acid derivative that specifically inhibits the function of the 26 S proteasome. It is the first proteasome inhibitor to be evaluated in human studies
5-9
. Bortezomib by injection has been approved for the treatment of multiple myeloma in selected patients
10
. Several studies on the anticancer and chemosensitization effects of bortezomib in pancreatic cancer have shown that it has significant activity
in vitro
and
in vivo
. However, the molecular mechanisms underlying proteasome inhibitor-mediated antitumor effects on pancreatic cancer are poorly understood, although possible explanations include inhibition of the NF-kB pathway
11
.
DAP (death-associated protein) kinase also participates in apoptosis, since its reduced expression by antisense mRNA protected HeLa cells from apoptosis induced by interferon-
γ
12
. In addition, overexpression of DAP kinase induced apoptosis and kinase-negative mutant-blocked apoptosis triggered by interferon-
γ
13
. DAP kinase-related apoptosis-inducing protein kinase 1 (DRAK1), which belongs to the DAP kinase subfamily of serine/threonine kinases, can induce the morphological changes of apoptosis in NIH 3T3 cells
14
. In our previous study
15
, oligonucleotide microarray analysis showed that DRAK1 responded to bortezomib in panc-1 and bxpc-3 cell lines. In the present study, we confirmed that bortezomib could potentiate the antitumor effects of gemcitabine against pancreatic cancer cells growing
in vitro
by up-regulating DRAK1.
Materials and methods
Drugs and chemicals
The 26S-proteasome inhibitor bortezomib was kindly provided by Dr. Jiangping Wu (Laboratory of Immunology, Research Center, CHUM-Notre Dame Hospital, Montreal, Canada). The agent was dissolved in dimethyl sulfoxide (DMSO) to make a 0.2 mmol/L stock solution and stored at -80 °C. Bortezomib was diluted in culture medium immediately before use. In all experiments, the final concentration of DMSO did not exceed 0.1%. Gemcitabine was purchased from Eli Lilly and dissolved in sterile 0.9% sodium chloride to make a 50 g/L stock solution.
Cell lines and culture
panc-1 and bxpc-3 human pancreatic cancer cell lines were obtained from the American Type Culture Collection and cultured in Dulbecco’s modified Eagle’s medium supplemented with 10% fetal calf serum, sodium pyruvate, nonessential amino acids and L-glutamine. Cells were maintained in a humidified atmosphere of 5% carbon dioxide at 37 °C and subcultured upon reaching 80% confluence.
Growth inhibition assay
Cells were plated in 96-well sterile plastic plates (100 µl/well at a density of 5
x
10
4
cells/ml) and allowed to attach for 24 h. Cells were then placed in media containing specified treatment regimens. At the end of the specified treatment period, cells were pulsed with 20 µl of 5 mg/ml 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT) (Sigma, St. Louis, MO, USA) in each well and incubated at 37 °C in 5% CO
2
for 4 h. The medium was aspirated, and the formazan crystals were dissolved in 150 µl of DMSO. Absorbance was measured at 570 nm using a spectrophotometer (BIO-Tek ELx800, Winooski, VT, USA). Growth inhibition was defined in relation to that of the untreated cells by the following equation: [growth inhibition (% control) = 100 × (absorbance untreated sample -absorbance treated sample)/(absorbance untreated sample)]. For each concentration and combination, experiments were repeated three times, and each experimental condition was repeated in quadruplex wells in each experiment.
Cell cycle analysis
Cell cycle analysis and quantification of apoptosis analysis was carried out using propidium iodide (PI) staining and fluorescence-activated cell sorting (FACS). In brief, panc-1 and bxpc-3 cells cultured for 24 h in gemcitabine (50
μ
g/ml and 0.05
μ
g/ml, respectively), bortezomib (100 nM), and combination and control media were collected by gentle trypsinization, washed in PBS, and pelleted by centrifugation. Cells were fixed in 70% ethanol and stored at -20 °C until staining. Immediately prior to staining, cells were washed twice in PBS and then resuspended in PBS containing RNAse A (20 µg/ml). Cells were then stained with PI (0.1 mg/ml) at room temperature in the dark for 30 min. DNA histograms were obtained by FACS using FACSCalibur with CellQuest 3.1f software (Becton Dickinson, San Jose, CA, USA). Cell cycle analysis was performed using Modfit 3.0 Program. Cell cycle progression was measured with corresponding absorbance for G
0-
G
1
, S, and G
2
-M phases. The relative percentage of cells in the sub-G
0
phase was then quantitated and used as an estimate of cells undergoing apoptosis. All the experiments were performed in triplicate.
Flow cytometric assessment of apoptosis
The measurement of phosphatidylserine redistribution in a plasma membrane was conducted according to the protocol outlined by the manufacturer of the Annexin V-FITC/PI apoptosis detection kit (Abcam, Cambridge, MA, USA). After a 24-h treatment, harvested 1
x
10
5
cells were suspended in 500 µl of 1
x
Annexin V binding buffer. Five µl of Annexin V-FITC and 5 µl of PI were added and the mixture incubated for 15 min in the dark. Binding buffer (1
x
) (400 µl) was added to each sample. The stained cells were analyzed directly by flow cytometry using the Cell Quest program (Becton Dickinson).
Reverse transcription-polymerase chain reaction
(RT-PCR) analysis and quantitative real-time RT-PCR
Total RNA was isolated with the reagent TRIzol (Invitrogen, Carlsbad, CA, USA) following the manufacturer’s instructions. RNA concentrations were determined by spectrophotometry. cDNAs were synthesized by moloney murine leukemia virus reverse transcriptase with oligo(dT)16 primer. Each reverse transcript was amplified with glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as an internal control. RNA templates were used to generate cDNAs for DRAK1 (sense, 5’-TGACAAGTGAATCTCCATTGGGTG-3’; antisense, 5’-TGAAATCAACAGCCGACTCAGAC-3’) and GAPDH (sense, 5’-AACGGATTTGGTCGTATTGGG-3’; antisense, 5’-TCGCTCCTGGAAGATGGTGAT-3’) by PCR. RT-PCR was performed by a DNA thermal cycler (BIO-RAD, Hercules, CA, USA). The PCR products were visualized on 2% agarose gels with ethidium bromide staining under UV transillumination.
Fluorescent PCR analysis was performed using the BIO-RAD iCycler 5 (BIO-RAD). RNA was amplified by qPCR in 20 µl reactions using SYBR
®
Premix Ex TaqTM (TAKARA Biotechnology, Dalian, China) with 10 µmol of each appropriate primer (sense, 5’-TGAACCTGTCAAAGCACCTG-3’; antisense, 5’- ACCTGGTTGTCTGAAGTGCC-3’). Assays were performed in triplicate and analyzed using I cycler version 3.1.7050 (BIO-RAD). The gene expression levels obtained were normalized by mRNA expression of GAPDH. The relative mRNA expression was then presented in relation to the control.
Western blotting
Cells were grown at 1×10
6
cells and incubated with special agents for the indicated times. Following treatment, cells were washed with PBS, and total cells were prepared by scraping in 200 μl of lysis buffer (50 mM Tris–HC, pH 8.0, 1.0 mM ethylenediaminetetraacetate, 150 mM NaCl, 0.1% SDS, 1% NP40, 1% sodium deoxycholate, 1 mM phenylmethanesulfonylfluoride). Fifty micrograms of proteins were determined by using BCA protein assay kit (Pierce Biotechnology, Rockford, IL, USA). For protein analysis, total cellular lysates were separated on a 10% (w/v) SDS-polyacrylamide gel and transferred to polyvinylidene fluoride. The filters were blocked in tris-buffered saline with 5% skim milk and incubated overnight with primary antibodies specific for DRAK1, procaspase-3, poly (ADP-ribose) polymerase (PARP) (Santa Cruz Biotechnology, Santa Cruz, CA, USA) as a primary antibody. The filters were then incubated with secondary antibody conjugated with horseradish peroxidase (Santa Cruz Biotechnology). Immunoreactive bands were detected by the enhanced chemiluminescence kit for western blotting detection with hyper-ECL film. Equal loading was confirmed by probing the blots with the anti-
β
-actin antibody (Santa Cruz Biotechnology).
Statistical analysis
Data were expressed as mean values ± SE and analyzed by a two-tailed
t
-test with
P
<0.05 considered as significant. Analyses were performed using SPSS 11.5 statistical software package (SPSS Inc., Chicago, IL, USA).
Results
Effects of bortezomib and gemcitabine
on growth of pancreatic cancer cells
To test the effects of bortezomib on pancreatic cancer cell growth, cells were treated with increasing concentrations of bortezomib (0-160 nM) for 24, 48 and 72 h. As shown in Figure 1A, panc-1 cell growth was inhibited by bortezomib treatment in a dose- and time-dependent manner. Low doses of bortezomib (20 and 40 nM) did not increase bxpc-3 cell growth inhibition for 24, 48 and 72 h. We subsequently evaluated the effect of gemcitabine on cell growth
in vitro
and found that gemcitabine was effective in inhibiting cell growth in both cell lines (Figure 1B). The results revealed that bxpc-3 was most and panc-1 least sensitive to gemcitabine-induced growth inhibition.
Bortezomib potentiates growth inhibition induced
by gemcitabine in pancreatic cancer cells
Next, the effect of a combination of bortezomib and gemcitabine on cell viability was investigated by MTT assay. For these studies, cells were treated with bortezomib (100 nM), gemcitabine (panc-1, 50 µg/mL; bxpc-3, 0.05 µg/mL) or the two-drug combination for 24 h. Viable cells were evaluated by MTT assay. We found that treatment with bortezomib plus gemcitabine for 24 h resulted in more growth inhibition than either bortezomib or gemcitabine alone in pancreatic cancer cells (Figure 1C).
Effects of bortezomib and gemcitabine on apoptosis
of pancreatic cancer cells and cells in the sub-G0 phase
bxpc-3 and panc-1 cells were treated with bortezomib (100 nM) or gemcitabine(0.05 µg/ml and 50 µg/ml, respectively) alone, or the combination of the two drugs for 24 h, and cell cycle analysis was performed as described. As shown in Figure 2A, combined treatment resulted in a significant increase in the number of cells in the sub-G
0
phase, compared with bortezomib and gemcitabine alone.
Whether bortezomib enhances the induction of apoptosis by gemcitabine was examined. We observed the induction of apoptosis in pancreatic cancer cells treated with bortezomib (100 nM) or gemcitabine (0.05 µg/ml and 50 µg/ml) alone or with the combination for 24 h. At these concentrations, relative to single agents, the combined treatment with gemcitabine and bortezomib for 24 h induced much more apoptosis in both the cell lines as shown by Annexin V/PI flow cytometry. Treatment with gemcitabine alone showed an apoptosis induction with 5.15% and 9.06% apoptosis in bxpc-3 and panc-1 cells, respectively. However, treatment with bortezomib alone demonstrated 11.45% apoptosis in panc-1 and 6.83% in bxpc-3 cells. Furthermore, the combination of gemcitabine and bortezomib resulted in a strong apoptotic effect. Panc-1 cells showed 15.42% apoptosis and bxpc-3 cells 11.11% (Figure 2B), suggesting that bortezomib is able to enhance the extent of gemcitabine-induced apoptosis.
To further examine the ability of the combination therapy to induce apoptosis, we evaluated procaspase-3 and PARP activation in both the tested cell lines. The combination of bortezomib and gemcitabine caused an additional increase in PARP cleavage and a decrease in procaspase-3 compared with either agent alone (Figure 2C).
Bortezomib upregulates DRAK1 in panc-1
and bxpc-3 cells
To investigate the mechanisms by which bortezomib induced apoptosis, we evaluated the expression of the apoptotic gene DRAK1 in pancreatic cancer cells after drug exposure. We first examined the mRNA levels of the gene in panc-1 and bxpc-3 cells using PCR. As shown in Figures 3A and 3B, treatment of panc-1 and bxpc-3 cells with bortezomib (100 nM) and gemcitabine (50 µg/ml and 0.05 µg/ml) induced an increase in the levels of DRAK1 mRNA compared with control and single treatment. Furthermore, immunblotting analysis in panc-1 but not in bxpc-3 cells showed similar changes in the expression of DRAK1 protein produced by the combination, suggesting that bortezomib enhanced cytotoxicity of gemcitabine by up-regulating the DRAK1 gene (Figure 3C).
Discussion
Pancreatic cancer is characterized clinically by a wide resistance to all current chemotherapy treatments. Previous studies have reported that human pancreatic cancer cell lines display marked resistance to gemcitabine
16
. Therefore, representative gemcitabine-sensitive (bxpc-3) and gemcitabine-resistant (panc-1) cell lines
17
were selected to evaluate the effects of bortezomib combined with gemcitabine on pancreatic cancer cell growth
in vitro
. Cell growth inhibition analysis revealed that panc-1 cells responded weakly and bxpc-3 cells showed high sensitivity to gemcitabine, whereas both responded to bortezomib. Next, we found that the combination of gemcitabine and bortezomib treatment markedly enhanced tumor cell growth inhibition compared with either agent alone.
Bortezomib is a potent and reversible proteosome inhibitor that functions to degrade intracellular polyubiquitinated proteins. It is an approved drug for the treatment of patients with relapsed multiple myeloma. Bortezomib induces apoptosis and has shown broad antitumor activity with selectivity for transformed cells
18-20
. Currently, many preclinical trials that researched the treatment of bortezomib in combination with gemcitabine in pancreatic cancer have shown various degrees of efficacy
21-23
, whereas the exact underlying mechanisms have not been fully delineated. Using oligonucleotide microarrays, we identified a large number of genes differentially expressed, some of which are potentially involved in bortezomib’s antitumor effects in pancreatic cancer and have not been previously reported
15
.
In our study, analysis of apoptosis demonstrated differential responses of individual cell lines to treatment with bortezomib, whereas the combination led to greater apoptosis in both gemcitabine-sensitive (bxpc-3) and gemcitabine-resistant (panc-1) cell lines. However, no difference was observed when the two (gemcitabine and bortezomib) were used alone. Potentiation of gemcitabine-induced apoptosis by bortezomib in pancreatic cells was validated by procaspase-3 activity and PARP cleavage. Moreover, in our results, we first found that bortezomib, but not gemcitabine, was able to induce DRAK1 in both cell lines, providing a molecular link between proteosome inhibition and activation of DAP kinase-related apoptosis-inducing kinase 1.
Sanjo
et al.
14
identified two additional members of the DAP kinase family (designated as DRAK1 and DRAK2) whose catalytic domains are related to that of DAP kinase, a serine/threonine kinase involved in apoptosis. Both DRAKs are composed of an N-terminal catalytic domain and a C-terminal domain responsible for the regulation of kinase activity. The kinase activity of DRAK1 is significantly stronger than that of DRAK2. Overexpression of DRAK1 and DRAK2 induced the morphological changes of apoptosis, as did DAP kinase and ZIP kinase
14
. It was previously shown that the cell apoptosis gene DRAK1 has an interesting expression pattern after exposure to etoposide in MeWo cells, and down-regulation of DRAK1 was observed in L-OHP-resistant cells by microarray experiments. A positive relationship between DRAK1 and L-OHP or etoposide resistance in human cancer cell lines was suggested, implying that the lower expression of DRAK1 might be associated with drug resistance
24, 25
.
In our studies, PCR and western blot analysis showed that DRAK1 was rarely expressed in gemcitabine-sensitive cell lines (bxpc-3) and gemcitabine-resistant (panc-1) cell lines. The mRNA levels of DRAK1 could be significantly upregulated by treatment with bortezomib in both cell lines. In contrast to bortezomib, mRNA levels of DRAK1 were only induced by gemcitabine in bxpc-3 cell lines, suggesting that DRAK1 may be related to
with gemcitabine resistance. Compared with either treatment, co-treatment with bortezomib and gemcitabine markedly enhanced the mRNA levels of DRAK1 in both cell lines. On the one hand, no significant change in DRAK1 was observed by western blot analysis between treatment with combination therapy and treatment with bortezomib alone in bxpc-3 cell lines. On the other hand, we found that the combination of bortezomib with gemcitabine strongly upregulated DRAK1 in gemcitabine-resistant (panc-1) cell lines, indicating that the ability of bortezomib to upregulate DRAK1 might be an important mechanism by which it was able to enhance gemcitabine-inducing apoptosis and overcome gemcitabine resistance in pancreatic cancer cells.
In conclusion, results from our study first indicate that bortezomib can potentiate the apoptotic effect of gemcitabine and overcome gemcitabine resistance in pancreatic cancer cells by inducing DRAK1. Up-regulation of DRAK1 could provide new strategies to treat pancreatic cancer, especially gemcitabine-resistant pancreatic cancer. Although prospective trials are needed to determine the actual benefits, DRAK1 might be a new target gene in the therapeutic course of pancreatic cancer.
biblio_titolo -
ignora
References
bibliografia -
art_bibliografia
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Angiogenesis c-erbB-2
Angioimmunoblastic lympha
Angiomyolipoma
angiosarcoma
anorectal function
Anorexia
antagonist
anthracycline
anthracycline therapy
anti-Hu
Anti-smoking legislation
Anti-TPO antibodies
antiangiogenic therapy
antidepressant drugs
Antiemetic prescriptions
antiemetics
Antiestrogens
antineoplastic agents
Antineoplastic drugs
antioxidants
antiproliferative action
Antiretroviral therapy
antisense oligonucleotide
antismoking center
antithrombotic prophylaxi
antitumor agents
Antitumor immunity
anxiety levels
APC gene
apheresis
apolipoproteins
Apoptosis
appendiceal carcinoid tum
appendiceal mucinous neop
appendix
appendix mucinous neoplas
applicator position varia
appropriateness
apudomas
Argentina
aromatase inhibitors
array CGH
Arsenic trioxide
arsenic trioxide (As2O3)
Arterial hepatic infusion
artificial neural network
Asbestos
Asbestos exposure
Ascites
Ascites and omental disea
ASCUS
Askin tumor
assessment
astroblastoma
astrocytoma
astrocytomas
athymic mice
ATP-binding cassette subf
Atrial fibrillation
Atrial myxoma
attenuated familial adeno
attenuated Salmonella typ
atypical carcinoid
atypical lobular hyperpla
Atypical lymphocyte proli
atypical multiple scleros
Auditory
autograft
Autoimmune thyroid disord
Autologous and allogeneic
Autologous bone marrow tr
Autologous peripheral blo
Autologous stem cell resc
autonomic neuropathy
Autopsy
axillary dissection
axillary lymph node invol
Axillary lymph node metas
axillary lymph nodes
Axillary metastases
axillary radiotherapy
b-catenin
B-cell
b-cell lymphocytic leukem
B-cell NHL
BAG-1
Barrett's ablation
basal
Basal cell carcinoma
basal-like carcinomas
Basaloid squamous cell ca
Bax
Bayesian analysis
Bcl-2
BCL2
BCR-ABL
Bellini carcinoma
benchmarking issue
Benign breast disease
benign breast diseases
benign multicystic perito
Benzene
beta-2 microglobulin
beta-catenin
beta2-microglobulin
bevacizumab
beyond progression
BH3 domain
bilateral breast cancer
bile duct carcinoma
biliary
biliary obstruction
Bio-immunotherapy
biobank network
biochemical failure
biological resonance
Biomarker
Biomarkers
Biopsy
Biotherapy
Biphasic mesothelioma
Biphasic mixed tumors
Bisphosphonate
Bisphosphonates
Bladder
Bladder cancer
bladder carcinoma
Bladder function
bladder neoplasms
Bleomycin
Blood group antigens
Blue dye
BNIP3
body image
Body weight
bone
bone marrow
bone marrow aspirate
Bone metastases
Bone metastasis
bone tumor
bortezomib
Bowel obstruction
Brachytherapy
Brain
brain lesion
Brain metastases
Brain metastasis
brain tumor
Brain tumors
BRCA mutation
BRCA1
BRCA1 and BRCA2 genes
BRCA1/2
Breast
Breast cancer
Breast cancer diagnosis
Breast cancer phenotype
breast cancer recurrence
Breast cancer risk
Breast cancer screening
breast cancer subtype
Breast carcinoma
Breast edema
breast lesion
breast lump
Breast magnetic resonance
breast metastasis
breast neoplasm
Breast neoplasms
breast pain
Breast reconstruction
breast sarcoma
breast tumor
Breast vasculitis
Breast-conserving surgery
Breslow thickness
bronchial lavage fluid
Bronchiolitis obliterans
bronchopulmonary carcinoi
bronchoscopy
bronchoscopy specimen
C-erbB-2
c-ErbB2
Cachexia
Cadore
Calcitonin
Calibration
californium-252 neutron
Camurati-Engelmann diseas
Cancer
cancer antigen 125
cancer antisense therapy
cancer bleeding control
Cancer care facilities
cancer centre
cancer chemotherapy
cancer complication
cancer control
cancer control-planning
cancer cytogenetics
cancer diagnosis
cancer in spouses
Cancer incidence
cancer metastasis
Cancer mortality
Cancer pain
Cancer pain treatment
cancer prevalence,
cancer prevention
Cancer proteomics
Cancer registries
Cancer registry
cancer research
cancer research infrastru
cancer survival
Cancer therapy
cannabinoid receptor-1 ge
Capecitabine
capecitabine monotherapy
Capillary leak syndrome
carbon ion radiotherapy
carbon nanotubes
Carboplatin
Carcinoids
Carcinoma
Carcinoma erysipelatoides
Carcinomatosis
Carcinosarcoma
cardiac angiosarcoma
Cardiac dysfunction
Cardiac metastases
cardiac sarcoma
cardiac toxicity
cardiopulmonary bypass
Cardiotoxicity
carotid body tumor
carotid femoral and aorti
Case report
case-control studies
Case-control study
caspase-6
caspase-9
Castleman's disease
cathepsin
Cathepsin D
Catheters
caveolae
Cavernous hemangioma
cavernous liver angioma
CCEA
CCNU
CD-138
CD10
CD105 (endoglin)
CD117
CD34
CD4+
CD40
cd40 ligand
CD40L
CD44
CD8+
CD8+ T cell
CD99
CDX-2
Celiac disease
Celiac plexus block
cell cycle
cell cycle proteins
cell death
cell invasion
cell migration
cell proliferation
cell toxicity
Cell types related marker
cell-specific magnetic re
cellular therapy
Central nervous system pr
central venous devices
Cerebellar metastasis
cerebral meningioma
Cervical cancer
Cervical cancer epidemiol
Cervical carcinoma
cervical chordoma
Cervical dysplasia
Cervical intraepithelial
cervical intraepithelial
cervical node metastasis
cervical plexus
cervical squamous cell ca
Cervix
cetuximab
Changes in molecular biol
Chemoprevention
Chemoradiation
Chemoradiotherapy
Chemotherapy
Chemotherapy at the end o
chemotherapy toxicity
chemotherapy-induced
chemotherapy-induced naus
Chemotherapy-induced peri
Chest reconstruction
Childhood
Childhood cancer
children
China
cholesterol
Chondrosarcoma
Chordoma
Chorioallantoic membrane
Choroidal metastasis
Chromogranin A
chromogranin-A
Chromosomal aberration
chromosome 3
chronic leukemia
chronic myeloid leukemia
Chronomodulated infusion
Chronotherapy
chylous ascites
Cigarette smoking
CIN
Ciplatin
cirrhosis
Cisplatin
Cisplatin-resistant metas
CK 5/6
classic Kaposi’s sarcom
Classification
clear cell renal carcinom
Clinic-pathological aspec
Clinical and pathological
Clinical audit
Clinical features
Clinical indications
clinical indicators
Clinical practice
Clinical stage
clinical stage I
Clinical staging
Clinical trial
Clinical trials
Clonality
Clozapine
CMF
CMF regimen
co-culture
CO2 laser
coagulation
Cohort studies
Cohort study
Cohort stuudies
collecting duct carcinoma
Colo-anal anastomosis
Colon
Colon adenocarcinoma
Colon cancer
Colon carcinoma
colon carcinoma metastasi
Colon metastases
Colonic adenocarcinoma
Colonoscopy
color Doppler sonogram
colorectal
Colorectal adenocarcinoma
Colorectal cancer
colorectal cancer liver m
Colorectal carcinoma
Colorectal neoplasms
colorectal screening
colorectal surgery
Colorectal tumor
Colorectal tumors
colposcopy
combined chemoradiotherap
Combined modality therapy
Combined modality treatme
Combined therapy
combined tumor
Combined-modality treatme
Comet assay
commissioning
common diagnostic pitfall
communication
communication of bad news
comorbidity
comparative genomic hybri
Comparative studies
Competitive PCR
complementary medicine
Complete response
Complications
composite hemangioendothe
comprehensive geriatric a
comprehensiveness
Computed tomography
computed tomography (CT)
computer-assisted reading
Computerized tomography
concomitant
concomitant boost
concomitant radiochemothe
CONCORD
Concurrent boost radiothe
Concurrent chemo-radiothe
concurrent chemoradiother
Conflict of interest
conformal boost
conformal external beam r
Conformal radiotherapy
congenital breast malform
Conization
conservative management
Conservative radiotherapy
Conservative surgery
Conservative treatment
consolidation chemotherap
continuous 5-fluoruracil
Continuous infusion
Contrast enhancement
coordination
Cordoba
Core biopsy
core needle biopsy
Coronary ostial stenosis
Correct sun exposure
cosmesis
Cosmetic results
cost
cost-effectiveness
cotyledonoid dissecting l
cox-2
coxofemoral arthrodesis
CpG island methylation
Cranial metastases
cranial trauma
craniospinal irradiation
cribriform carcinoma of t
cricoid cartilage
cricoid tumor
Croatia
cross-talk
Crude rates
Cryoglobulinemia
Crystal-storing histiocyt
CT
cultural diversity
Curettage mastectomy
Cushing's syndrome
Cutaneous melanoma
cutaneous tumors
cyberKnife
cyclooxygenase-2
cyclophosphamide
cyst
cystadenocarcinoma
cystatin
cystectomy
Cystic components
cystic hygroma
cystic lymphangioma
Cystic mesothelioma
cystic neuroendocrine pan
Cystoprostatectomy
cytarabine
Cytogenetic analysis
Cytogenetic biomarkers
cytogenetics
Cytokine
Cytokines
cytology
Cytomegalovirus
Cytoreduction
Cytoreductive surgery
Cytotoxic granules
cytotoxic T lymphocytes
dacryocystitis
DAPI
DAPk
Daunorubicin
De novo
de novo colon cancer
dead children
Deep venous thrombosis
Delayed onset
delays in diagnosis
Delivery
Dendritic cells
Dendritic cells inflammat
dental factors
Depression
Dercum’s disease
dermatofibrosarcoma protu
Dermoid cyst
Dermoscopic diagnosis
Dermoscopy
Desmoid tumor
Desmoid tumors
desmoplastic small round
Desmoplastic small round-
Desmoplastic tumor
detergent resistant micro
dexrazoxane
DFMO
diabetes
diabetes insipidus
Diagnosis
diagnosis disclosure
diagnostic imaging
diagnostic laparotomy
diagnostic odds ratio
dialysis
Diet
Dietary questionnaire
differential diagnosis
Differentiated thyroid ca
Differentiated thyroid ca
Diffuse gastric cancer
diffuse large B-cell lymp
Dihydrotestosterone
Diplopia
Discomfort
disease management
disease progression
disease-free period
disease-oriented bioban
disseminated intravascula
distance education
Distant metastases
DNA
DNA binding
DNA damage
DNA methylation
DNA microarrays
DNA ploidy
DNA repair
DNA sequencing
docetaxel
Dose calculation algorith
Dose fractionation
dose intensification
dose-dense chemotherapy
dose-finding study
dose-intense
Dose-intensity
Dose-volume histograms
Dosimetric calibration
dosimetric variation
Down syndrome
Down-staging
downdose
Doxorubicin
Doxycycline
DRAK1
Drinking habits
drug delivery
Ductal adenocarcinoma
Ductal carcinoma in situ
Ductopenia
duodenal
Duodenal neoplasm
Duodenocephalo-pancreasec
duodenum
Dural involvement
duration of treatment
DVL1
dynamic micro-multileaf c
dysphonia
dyspnea
Dysproteinemia
E-cad
E-cadherin
E-selectin
Early breast cancer
Early cancer
Early diagnosis
early gallbladder carcino
Early glottic carcinoma
Early polypoid colorectal
early rectal cancer
early stage
Early stage lung cancer
early technology assessme
eccrine mucinous adenocar
Ecological monitoring
Ectopic
ectopic breast
Ectopic pregnancy
Edema
Educational level
Educational message
EGFR
eLAV-like protein
Elderly
elderly cancer patients
elderly patient
Elderly patients
elective nodal irradiatio
electrocardiogram
electrochemotherapy
electromagnetism (EM)
electromyography
electronic chart
electroporation
Embolization
Emergency surgery
en bloc resection
Encephalopathy
end of life
End-of-life care
end-stage renal impairmen
endocrine system
Endodermal sinus tumor
endoG expression
endogenous porphyrins
Endometrial cancer
Endometrial carcinoma
endometrial tumor
Endometrium
Endoscopic ablation
endoscopic removal
endoscopy
Energy expediture
Engineered tumor cells
Enhancement
Enoxaparin
enteric nervous system
enterocutaneous fistula
Environmental exposure
Environmental pollution
Environmental tobacco smo
EORTC questionnaire
ependymomas
EPIC
epidemiologic methods
Epidemiology
epidermal growth factor
epidermal growth factor r
Epigenetic alterations
Epigenetics
Epirubicin
epithelioid
Epithelioid sarcoma
Epo
Epoetin alfa
Epstein-Barr virus
Epstein-Barr virus (EBV)
ER
era
erB-2
erlotinib
errors in radiation deliv
erythroleukoplakia
Erythropoietin
Esophageal adenocarcinoma
Esophageal cancer
Esophagogastroscopy
Esophagus
esophageal cancer
esthesioneuroblastoma
estrogen receptor
estrogen-progesterone rec
Ethics
Ethics committees
Ethmoid cancer
Ethnic distribution
European Union
euthanasia
event tree model
evidence-based medicine
Ewing sarcoma
Ewing's sarcoma
Ewing’s sarcoma
Ewing’s sarcoma family
exemestane
Exercise testing
exonic splicing enhancers
exosomes
experimental
extended cholecystectomy
External beam radiotherap
Extra-abdominal metastasi
Extracapsular extension
Extracellular matrix prot
Extradonal non-Hodgkin's
Extragonadal germ cell tu
extramedullary plasmacyto
Extranodal lymphoma
extranodal MALT lymphoma
Extraosseous Ewing's sarc
extraosseous sarcoma
Extrapulmonary small cell
Extravasation
eyelid
ezrin
facial nerve
false positive
Familial adenomatous poly
Familial polyposis
families
family
Fas/FasL
fatigue
FDG-PET
feasibility
febrile neutropenia
Female
fetal dose
FHIT gene
Fibroma
fibromatosis
fibronectin
fibrosis
filgrastim
Finasteride
fine-needle aspiration cy
FISH
Fistula
fixed-dose-rate infusion
FLIPI
Floxuridine
fluorescence
Fluoropyrimidine-pretreat
Fluorouracil
FMF
focal adhesion kinase
Focal nodular hyperplasia
folate
FOLFIRI
folfox
FOLFOX IV/LV5FU2 chemothe
FOLFOX regimen
folinic acid
Follicular carcinoma
Follicular lymphoma
follicular thyroid cancer
follow-up
Food
Forearm
foregut neuroendocrine ca
Four or more positive axi
Fractionated stereotactic
fractionation
fraud
fullerenes
fulminant liver failure
G-CSF
galectin-1
galectin-3
Gallbladder
Gallbladder carcinoma
Gamma probe
Gamma-glutamyltransferase
gastrectomy
Gastric cancer
Gastric carcinoma
Gastric melanoma
gastric myoepithelial ham
gastrointestinal carcinoi
gastrointestinal interven
Gastrointestinal lymphoma
Gastrointestinal neoplasm
Gastrointestinal stromal
Gastrointestinal stromal
gastrointestinal stromal
gastrointestinal stromal
Gemcitabine
Gender differences
Gene expression
gene expression profile
gene polymorphism
gene therapy
General practitioners
Genetic research
genetic susceptibility
Genetic testing
Genetic tests
Genomic instability
genomics
genomics
GEP neuroendocrine tumors
germ cell tumor
germ cell tumors
Germline mutations
gestational trophoblastic
giant basal cell carcinom
giant follicles
giant keratoacanthoma
Giant mixed retroperitone
Giemsa
GIST
glioblastoma
Glioblastoma multiforme
Gliofibroma
Glioma
gliosarcomas
Glottic cancer
glucagon
glucose-6-phosphate dehyd
glutamine
glutathione S-transferase
glycoproteins
Gonadoblastoma
good clinical practice
Good's syndrome
GPI
granular cell tumor
granulocyte-colony stimul
granulocytic sarcoma
Granulomatous angiopannic
Granulomatous gastritis
Graves' disease
growth inhibitory peptide
growth rate
GSTP1
guidelines
Guillain-Barré syndrome
Gynecomastia
Gynecomastia and hormone
Gynecomastia and prostate
H. pylori
Hadron therapy
hairy cell leukemia
half-body irradiation
hamartoma
Hand-foot syndrome
Hashimoto’s thyroiditis
HBV/HCV infections
HCV
HDR brachytherapy
Head and neck
Head and neck cancer
Head and neck carcinoma
Head and neck malignancie
head and neck neoplasms
head and neck tumor
Head trauma
Health-related quality of
healthy donors
Heart
heart failure
heart transplantation
heat
heat shock protein 70
heavily pretreated
Hemangioendothelioma
Hemangiopericytoma
Hemangiosarcoma
Hematological malignancie
hematological malignancy
Hematopoietic stem cell t
hematuria
Hemodialysis
Hemoglobin levels
hemoperitoneum
hemophilia A
Hep-2 cells
Heparin
Hepatic adenosquamous car
Hepatic arterial infusion
Hepatic arterial infusion
Hepatic artery
hepatic tumor
Hepatitis B virus
hepatitis B virus (HBV)
Hepatitis B virus integra
Hepatitis C virus infecti
hepatoblastoma
Hepatocellular
Hepatocellular carcinoma
hepatocellular carcinoma
hepatocyte growth factor
HER-2
HER-2 receptor
HER-2/neu
HER2
HER2-positive metastatic
Herceptin
Hereditary breast cancer
hereditary non-polyposis
HEY1
high dose
High dose chemotherapy
high dose rate
high genetic risk
high-dose boost
High-dose chemotherapy
high-dose epirubicin
High-dose rate brachyther
high-grade glioma
High-grade squamous intra
high-risk medulloblastoma
Histogenesis
histological diagnosis
Histological score
HIV
hMLH1
hMLH1 hypermethylation
HNPCC
Hodgkin disease
Hodgkin's disease
Hodgkin's disease (HD)
Hodgkin’s disease
Home palliative care serv
homocysteine levels
Horizontal growth phase m
Hormone receptor status
Hormone refractory
hormone replacement thera
Hormone therapy
Hormone-refractory prosta
Hormonorefractory
Hormonotherapy
Hospital
Hospital-based population
HPV
Hrthle cell carcinoma
hTERT
hu-PBL/SCID chimera
huge hepatocellular carci
Human
human carboxylesterase-2
Human chorionic gonadotro
Human Epo receptor (EpoR)
Human G-CSF receptor
Human immunodeficiency vi
Human papilloma virus
Human papillomavirus
human sarcoma
Human tumor cell lines
hur
hydration
hydrocele
Hydrogen peroxide
hydronephrosis
Hypercoagulable state
Hypereosinophilic idiopat
Hyperfractionated radioth
Hyperfractionation
Hyperparathyroidism
Hypersensitivity reaction
Hypertermic tissue ablati
hyperthermia
Hypocalcemia
Hypofractionation
Hypoparathyroidism
hypopharyngeal cancer
hypothyroidism
ICCC-3
ICD-10
Id2 protein
Idiopathic thrombocytopen
IFN-a-2a
Ifosfamide
IgR
IHH
IL-12
IL-2
ileal carcinoid
ileal mucosa
image analysis
image fusion
Image probing
image-guided intensity-mo
Image-guided radiotherapy
imaging
imatinib
Imatinib mesylate
imiquimod
immune host response
Immunity
immunocompetent host
immunocytochemistry
Immunodeficiency
immunohistochemical analy
Immunohistochemical marke
Immunohistochemistry
Immunoradiometric assays
Immunoscintigraphy
Immunotherapy
impact factor
Implantable port
IMRT
in vivo imaging
in vivo small animal magn
inappropriate doses of ch
incentives
Incidence
incidence rates
Independent studies
induced lymphoma
induction chemotherapy
induction therapy
infant
infantile myofibromatosis
infection
Infections
infectious agents
infiltrating ductal carci
Inflammation
Inflammatory bowel diseas
Inflammatory breast carci
Inflammatory mechanism
Inflammatory metastatic c
inflammatory myofibroblas
inflammatory pseudotumor
Informed consent
infrastructures
infusion reaction
Infusional chemotherapy
infusional therapy
Inguinal canal
Inguinal hernia
Inoperable bowel obstruct
insular
Insular thyroid carcinoma
Insurance
integral dose
Integrated radiotherapeut
integration
integrin beta 3
intensity modulated radia
Intensity-modulated exter
Intensity-modulated radia
Intensity-modulated radia
intensity-modulated radio
Interaction
Interactive computer grap
Interferon
interferon beta
Interleukin-2
Interleukin-6
interleukins
Intermediate emetogenic c
internal mammary node met
international collaborati
international cooperation
International Prognostic
internet
Interobserver agreement
Interpectoral (Rotter's)
interstitial pneumonitis
interval cancer
interval cancers
interval censoring
Interventional radiology
intestinal permeability
intestinal pouch
intima-media thickness
Intra-arterial chemothera
intra-operative radiother
Intraabdominal tumor mass
Intracranial tumors
Intraductal carcinoma
Intrahepatic cholangiocar
Intrahepatic cholestasis
intramedullary metastases
intramedullary tumor
intraoperative pathologic
Intraoperative radiothera
intraosseous hemangioma
Intraperitoneal chemother
intraperitoneal chemoth
Intraperitoneal hyperther
intratumoral lymphocyte
Intravascular lymphomatos
Invasion
Invasive ductal carcinoma
invasiveness
Ionizing irradiation
IORT
Iran
Irinotecan
iris metastasis
iron oxide nanoparticle
isolated splenic metastas
isothiocyanates
Italian cancer burden
Italian cancer control
Italian EPIC population
Italian Sarcoma Group
Italy
jaw
jaws
jejunal intussusception
Job's syndrome
joinpoint analysis
Juvenile granulosa cell t
K-ras
k-ras codon 12 mutation
Kaposi's sarcoma
Kaposi’s sarcoma
keratin
Keratin/genetics
keratoacanthoma
Ki-67
Ki-67 antigen
Ki-ras gene
Ki67
Kidney
kidney transplantation
KIT
kit protein
Korea
Krukenberg tumor
Kyphoplasty
lab-on-chip
labelling
Lacrimal sac
Lactulose-mannitol test
Laminin
lamivudine
Laparoscopic cholecystect
laparoscopic splenectomy
Laparoscopic surgery
laparoscopy
Large breast
laryngeal cancer
laryngeal chondrosarcoma
Laryngeal neoplasm
larynx
Larynx carcinoma
late brain metastases
late complication
Late effects
late effects of cancer tr
late relapse
Late side effects
Late toxicity
latent membrane protein 1
Leading cancer sites
Leiomyosarcoma
leptomeningeal metastases
Leucovorin
Leydig cell tumor
Li-Fraumeni syndrome
life tables
Life-style
Life-style questionnaire
Limited stage
lipid-rich carcinoma
Liposarcoma
Liposomal doxorubicin
Liposomes
Liquid-based cytology
literature review
Liver
liver cancer
liver failure
Liver malignancies
Liver metastases
Liver metastasis
liver neoplasm
Liver resection
Liver transplantation
Liver tumors
lobectomy
Lobular carcinoma
lobular carcinoma in situ
lobular neoplasia
Local control
Local recurrence
local tumor recurrence
local-regional recurrence
localized carcinoma of th
localized gastrointestina
localized non-Hodgkin's l
Locally advanced
Locally advanced breast c
Locally advanced breast t
Locally advanced disease
locally advanced lung can
Locoregional chemotherapy
Locoregional radiotherapy
Lomustine
Long-surviving patient
long-term complications
long-term follow-up
Long-term outcome
Long-term remission
Long-term survival
Long-term-survivors
loss of heterozygosity
loss of heterozygosity (L
Loss of heterozygosity,
low dose intensity
low dose rate
lumpectomy
Lung
Lung adenocarcinoma
Lung cancer
lung cancer prognosis
Lung carcinoma
Lung metastases
lung metastasis
Lung neoplasm
Lung neoplasms
lung resection
lung toxicity
lymph node
lymph node diameter
Lymph node excision
Lymph node failure
Lymph node metastases
lymph node sampling
Lymph node status
Lymph node-negative breas
Lymph nodes
Lymphadenectomy
Lymphangioleiomyomatosis
lymphatic mapping
lymphocytes
lymphofollicular infiltra
Lymphoma
Lymphoscintigraphy
MAb CIBCgp185
macrophage
Magnetic resonance
Magnetic resonance imagin
maintenance chemotherapy
major surgery
Male breast cancer
Male breast carcinoma
Malignancy
malignant breast disease
malignant fibrous histioc
Malignant fibrous histioc
malignant giant cell tumo
malignant glioma
malignant gliomas
malignant infiltration of
Malignant melanoma
malignant mesenchymoma
malignant mixed mesoderma
Malignant pericardial tum
malignant peripheral nerv
Malignant pleural Mesothe
malignant thymoma
Malignant transformation
Malnutrition
MALT lymphoma
mammary phyllodes tumor
Mammography
mammography screening
Mandibular metastasis
Mandibular tumors
manifestation
mantle cell lymphoma
Margin involvement
mastalgia
mastectomy
matrix metalloproteinase-
matrix producing carcinom
Mature cystic teratoma
maxillary sinus
MCC
Mediastinal radiotherapy
mediastinal staging
Mediastinum
medical choice
Medical ethics
medical oncologist’s tr
medullary breast cancer
medullary carcinoma
Medullary thyroid cancer
Medullary thyroid cancer
Medullary thyroid cancer
Medullary thyroid carcino
Medullary thyroid carcino
Medullary thyroid carcino
Megestrol acetate
Melanin
melanocytoma
melanoma
Melanoma prevention
Membranous glomerulonephr
MEN 2 syndromes
MEN 2A
MEN 2B
meningeal carcinomatosis
Meningeal hemangiopericyt
Meningioma
Menopause
Menstrual cyles
menstrual induction
mental adaptation to canc
Merkel cell carcinoma
mesenchymal chondrosarcom
mesenchymal tumor
mesenteric cyst
Mesenteric fibromatosis
Mesenteric paraganglioma
Mesenteric thrombosis
mesentery
Mesothelioma
Meta-analysis
metacarpal bone
metachronous metastasis
metaiodobenzylguanidine s
Metaiodobenzylguanidine t
metallic implants
metalloproteinase
metallothioneins
Metanephrines
metaplastic carcinoma
metastasectomy
Metastases
Metastasis
metastasis of unknown ori
metastasis to stomach
Metastatic bone disease
Metastatic breast cancer
Metastatic cancer
metastatic cancers
Metastatic colorectal can
metastatic gastric cancer
metastatic liver disease
metastatic non-small cell
metastatic ovarian tumor
Metastatic prostate carci
Metastatic spinal cord co
metatarsal bones
methodological approaches
methylation
Methylene blue
metronomic therapy
MGMT
mice
microcalcification
Microcalcifications
Microenvironment
micropapillary
Microvascular density
Midline lymphoma
Minimal change disease
minors
Mismatch repair genes
mitogen-activated protein
mitomycin C.
mitomycin-C
Mitoses
mitotic catastrophe
Mitotic index
Mitoxantrone
Mixture models
MLH1
MMP
mobility
molecular diagnostics
Molecular follow-up
Molecular markers
monoclonal antibody
mononuclear cell migratio
Morbidity
morbidity-mortality
Mortality
Moschcowitz's disease
Motility
MRI
MSH2
MTA
MTHFR
mucinous adenocarcinoma
mucinous tumors
Mucosa-associated-lymphoi
mucosal damage
mucosuria
multi-drug resistance
multi-drug resistance pro
multicentric trial
multidisciplinary treatme
multiendocrine failure
multikinase inhibitor
multileaf collimator
Multimodality therapy
multimodality treatment
multiple bladder-prostate
multiple endocrine neopla
Multiple lymphangiomas
multiple malignancies
Multiple malignancy
Multiple myeloma
multiple primary cancers
multiple sclerosis
Multipurpose surveys
Multivariate analysis
Muscle cell proliferation
mutation
myasthenia
mycosis fungoides
myelodysplastic syndrome
myeloid markers
myocardial metastasis
myocardial perfusion defe
myocardial perfusion scin
myoepithelial cells
myoid
Na+-I- symporter
nanomedicine
nanoparticles
nanotechnology
nanomedicine
nanoparticles
nasal septum
Nasopharyngeal cancer
Nasopharyngeal carcinoma
nasopharyngeal neoplasm
Nasopharynx
National survival estimat
Natural killer cells
Neck
neck dissection
neck mass
neck metastases
Neck's tumors
necrosis
negative second-look lapa
neoadjuvant
neoadjuvant chemoradiatio
Neoadjuvant Chemotherapy
neoadjuvant radiotherapy
Neoadjuvant therapy
neoadjuvant,Taxotere
Neoplasm
Neoplasm circulating cell
neoplasm metastasis
Neoplasms
neopterin.
Neovascularization
nephrectomy
Nephrotic syndrome
nephrotoxicity
Nerve-sparing
Network
networks
neural tissue
neurilemmoma
Neuroanatomy
neuroblastoma
neuroendocrine carcinoma
Neuroendocrine differenti
Neuroendocrine tumor
Neuroendocrine tumors
neurofibromatosis 2
neurogliocytoma
Neurological state
Neuron-specific enolase
Neuropathic pain
neurosurgery
neurotoxicity
neutropenia
neutropenic enterocolitis
New bisphosphonates
new schedule
NF-ÛB
NF1
nipple-sparing mastectomy
NIS expression
NIS therapy
Nitric oxide
NK activity
NK cells
NK lymphoma
nm23
Nodal regions
nomograms
Non-functioning adrenocor
non-Hodgkin disease
Non-Hodgkin lymphoma
non-Hodgkin lymphomas
non-Hodgkin’s lymphoma
non-melanoma skin cancers
non-non-Hodgkin's lymphom
Non-palpable breast lesio
Non-palpable thyroid nodu
non-pegylated doxorubicin
Non-platinum chemotherapy
Non-profit clinical trial
non-seminoma
Non-smal cell lung cancer
Non-small cell lung cance
non-small cell type
non-small-cell lung cance
non-viral vectors
Nongestational choriocarc
nonlinear resonance inter
nonpigmented ciliary epit
nonseminomatous germ cell
norcholesterol scintigrap
Nosocomial infections
Nottingham prognostic
novel mutations
NSCLC
Nuclear medicine therapy
nucleic acid delivery
nutrient mixture
nutritional status
Obesity
obscure digestive bleedin
Occult blood
Occult primary
occult/obscure gastrointe
occupational exposure
octreoscan
Octreotide
Ocular
ocular adnexal lymphoma
odontogenic tumors
off-label
older population
oligonucleotides
omentum
Omentum.
Oncocytic neoplasm
oncogene
oncogenes
Oncogenomics
Oncology
Opioid consumption
opportunistic screening
optical biopsy of cancer
optical imaging
optical neuritis
Optimized screening
oral cancer
oral cavity
Oral mucositis
oral precancerous conditi
oral UFT (tegafur-uracil)
oral vinorelbine
orbit
Orbital involvement
Orbital metastasis
Orbital surgery
organisation of care
Orgotein
Oropharynx
Orthovoltage therapy
osteo-oncology
Osteoclastic activation
osteonecrosis
osteopetrosis
osteopontin
Osteosarcoma
osteosarcoma of the kidne
osteosarcomatous differen
outcome
outpatient regimen
Ovarian cancer
Ovarian carcinoma
ovarian endometriosis
ovarian malignancy
ovarian psammocarcinoma
ovarian teratoma
Ovarian tumor
Ovary
over-treatment
overall survival
Overdose
Overexpression
Oxaliplatin
oxidative phosphorylation
p105
p14
p16
p185HER2
p27Kip1
p53
p53 antibodies
p53 gene
p53 mutation
p53 protein
p57Kip2
p63
p73
Pacemaker
Paclitaxel
Paclitaxel-carboplatin
Paget’s disease
PAI-1
Pain mechanisms
painful lipomas
palliative care
palliative care in oncolo
Palliative chemotherapy
palliative radiation ther
palmar-plantar erythrodys
palonosetron
pancreas
Pancreatic cancer
pancreatic carcinoma.
pancreatic cyst
pancreatic ductal adenoca
pancreatic heterotopy of
pancreatic intraductal pa
Pancreatic metastases
pancreatic neoplasm
pancreatic neoplasms
Pancreatic resection
pancreaticoduodenectomy
panitumumab
Pap smear history
Pap smear screening
Pap smears
Papillary carcinoma
Papillary fibroelastoma
papillary thyroid carcino
Paraganglioma
paralytic ileus
parametric model
paranasal sinuses
Paraneoplastic nephrotic
Paraneoplastic neurologic
Paraneoplastic syndrome
Paraplegia
Paraspinal tumors
Parathyroid
parathyroid adenoma
Parathyroid carcinoma
Parathyroid hormone (PTH)
Parathyroidectomy
Parenteral nutrition
parotid carcinoma
parotid gland
parotid neoplasm
partial laryngectomy
pathology
Pathology related markers
Pathway
patient satisfaction
patient-physician relatio
patterns of care
Patterns of failure
paxillin
PCR
PDGF
PEComa
pediatric
pediatric oncology
pediatric tumors
pegfilgrastim
Pegylation
Pelvic CT
Penile metastases
perfusion
Periampullary stromal tum
perineal prostatectomy
Perioperative radiotherap
Peripheral blood progenit
peripheral blood stem cel
peripheral leukocytes
peritoneal carcinomatosis
Peritoneal mesothelioma
Peritoneal
cancer
Peritonectomy
Peritoneovenous shunt
Peritoneum
peritumoral hepatic tissu
perivascular epithelioid
Permanent prostate Brachy
PET
PET sensitivity
PET.
PET/CT
Pharmaceutical industries
pharmacoeconomics
Pharmacoeconomy
pharmacogenetics
Pharyngolaryngeal squamou
Phase I
Phase II study
Pheochromocytoma
Pheochromocytoma treatmen
Phosphoinositide 3-kinase
photo excitation
Photofrin
Photosensitizer
phyllodes tumor
Physical activity
Physicians
physiotherapy
Pituitary adenoma
pituitary gland
pituitary gland metastasi
placental site trophoblas
planning study
Plasma fatty acid
plasmacytoid
Plasmacytoma
Plastic ring
Plastic surgery
Platinum
pleomorphic adenoma
Pleura
Pleural neoplasms
pleural small cell carcin
Pleurocentesis
Ploidy
Pneumonectomy
point mutations
point-of-care
Pollution
poly(butyl cyanoacrylate)
poly(lactide-co-glycolic
Polyamines
polychemotherapy
polycystic liver disease
Polymerase chain reaction
polymorphism
polymorphous
polysomy
ponicidin
population surveillance
Population survey
Population surveys
population-based
Population-based study
population-based survey
Porphyrins
port site recurrence
Positron emission tomogra
positron-emission tomogra
Post-irradiation sarcoma
Post-radiation osteosarco
Post-remission treatment
Post-traumatic glioma
Post-traumatic meningioma
Post-treatment CIN
Postoperative chemoradiat
postoperative radiochemot
Postoperative radiotherap
Postoperative therapy
PP1 inhibitor
PR
Practice guidelines
pRb
pre-operative chemotherap
Predictive value
Prednisone
Pregnancy
Preoperative chemoradiati
preoperative diagnosis
preoperative immunotherap
preoperative radiochemoth
Preoperative radiotherapy
pretreatment tumor lysis
Prevalence
prevalence of use of comp
prevention
Prevention and control
Priapism
Primary
primary adenocarcinoma
primary bilateral adrenal
primary central nervous s
primary chemotherapy
primary cultures
primary duodenal adenocar
primary hepatic leiomyosa
primary hyperparathyroidi
primary lung tumors
primary osteosarcoma
primary pancreatic lympho
primary systemic therapy
Primitive neuroectodermal
proctocolectomy
progesterone receptor
Prognosis
Prognostic factor
Prognostic factors
Prognostic markers
prognostic parameter
Prognostic score
proliferating trichilemma
Proliferation
proliferation index
prone position
Prophylactic total thyroi
Prospective cohort study
Prospective longitudinal
Prospective study
prostaglandin-endoperoxid
Prostate
Prostate adenocarcinoma
prostate biopsy
Prostate cancer
Prostate carcinoma
prostate neoplasms
Prostate specific antigen
prostate-specific antigen
Prostatectomy
Prostatic ducts
Prostatic neoplasm
prostatic neoplasms
protection
Protein microarray
Protein S
Proteomics
Proteomics technologies
Proton beams
proton therapy
PSA test
Pseudomyxoma peritonei
Psoriasis
psychosexuality
psychosocial
Psychosocial adjustment
psychosocial support
PTCA
PTEN
Pulmonary
Pulmonary adenocarcinoma
Pulmonary blastoma
Pulmonary fibrosis
Pulmonary lymphoma
pulmonary non-Hodgkin’s
Pulmonary valve
Pylethrombosis
pyogenic liver abscess
Pyrene
quality assurance
quality indicators.
quality of care
Quality of life
quality score system
Quantification
quantitative real time po
questionnaire
questionnaires
Radiation
Radiation safety
Radiation therapy
Radiation-induced meningi
Radiation-induced tumors
Radiation-induced
Radical hysterectomy
Radical nephrectomy
radical surgery
radiochemotherapy
Radiofrequency ablation
Radiograph
Radioguided surgery
Radioiodine therapy
radiologic diagnosis
radiologically dense brea
radiometabolic therapy
Radionecrosis
Radionuclide therapy
radioprotection
radiosensitivity
Radiosensitizer
radiosensitizing
Radiosurgery
Radiotherapy
Radiotherapy fractionatio
radiotherapy treatment
Radiotherapy treatment pl
radiochemotherapy
Raloxifene
Ralstonia pickettii
Raltitrexed
ramosetron
Random sample
randomized controlled cli
Randomized controlled stu
Randomized controlled tri
randomized phase III tria
RARb
rare entity
rash
RASSF1A tumor suppressor
RCC
Re-irradiation
reactive lymphoid hyperpl
reactive oxygen species
Recall colitis
receptor
receptors
recognization
recombinant human growth
Recombinant human thyrotr
record-and-verify systems
Rectal adenocarcinoma
Rectal cancer
rectal fistula
rectal injury
Rectal lymphomas
rectal neoplasms
Rectovaginal fistula
Rectovaginal septum
Rectum
rectus abdominis muscle
Recurrence
Recurrent
Recurrent carcinoma
Recurrent high-grade glio
recurrent ovarian cancer
Recurrent rectal carcinom
Reflux esophagitis
Regional chemotherapy
regional medical programs
Regional program
registries
regression
regression analysis
reirradiation
Relapse
relative survival
relative value
Renal cancer
Renal carcinoma
Renal cell cancer
Renal cell carcinoma
Renal failure
Renal metastasis
renal osteosarcoma
renal papillary carcinoma
Renomedullary interstitia
Reproductive factors
Resection
residual lesion
Resistant
resources
respiratory failure
RET oncoproteins
Ret tyrosine kinase
RET/PTC
Retinal metastases
retro-orbital granulocyti
Retroperitoneal liposarco
retroperitoneal mass
retroperitoneal tumor
retrorectal hamartoma
retrorectal tumors
retrospective study
review
rewards
rhabdomyosarcoma
Rheumatoid arthritis
rhuCD40L,TRAF
ring and tandem
risk factor
risk factors
Risk of cancer
RNA
RNA interference
Runx2
S-100 protein
s-phase fraction
S-phase fraction.
sacroplasty
Salivary gland
Salvage radiotherapy
salvage therapy
Sampling bias
Sarcoma
sarcomatoid renal cell ca
Sarcomatosis
Scalene lymph node
scalp
scalp cooling
Schwann cell
Schwannoma
SCID mice
Sclerosing hemangioma
Scoring
Screening
seasonality
Second line
Second malignancies
second primary cancer
second primary tumors
second-hand smoke
second-line
Second-line chemotherapy
secondary breast angiosar
secondary hemicolectomy
Secondary malignancies
secondary prevention
Secondary sarcomas
SEER program
Segmental duodenal resect
selection criteria
Selective estrogen recept
selective internal radiat
self-expanding stent
self-report assessment
seminal vesicle invasion
seminoma
Sensitivity
sentinel lymph node
Sentinel lymph node biops
Sentinel lymph node mappi
Sentinel node
Sentinel node mapping
sequence
sequence variant
sequence-specific primer
sequential chemotherapy
serum
Serum lactate dehydrogena
sestamibi
setup uncertainty
sex cord stromal tumor
Sex-specific rates
sexual dysfunction
SF-36 questionnaire
shoe worker
shoulder movement
shoulder syndrome
Signs
Silver staining
simple cholecystectomy
simultaneous care
simultaneous thyroid carc
Single agent
single nucleotide polymor
single nucleotide polymor
single strand conformatio
single-strand conformatio
single-strand conformatio
sinonasal cancer
siRNA
Sister Joseph's nodule
size
skeletal muscle
skin
skin cancer
Skin metastases
Skin neoplasms
skin squamous cell carcin
skin toxicity
Smac/DIABLO
Small bowel
Small cell carcinoma
Small cell lung cancer
Small cell lung carcinoma
Small intestine adenocarc
Small melanocytic skin le
Small melanoma
Small-cell lung cancer
Smoking
smoking ban
Smoking cessation
Smoking habits
social class
Socio-economic data valid
Sodium iodide
soft tissue sarcoma
Soft tissue sarcomas
soft tissue tumor
soft-tissue tumor
solid pseudopapillary neo
solid tumor
solitary fibrous tumor
Solitary plasmacytoma
somatostatin analogs
Somatostatin analogues
Somatostatin receptor sci
Somatostatin receptors
sorafenib
Sox9
Spain
Specificity
Sphincter saving procedur
sphincter-saving procedur
sphincter-saving surgery
spinal accessory nerve
spinal cord
spindle cell
spindle-cell carcinoma
spleen.
Splenectomy
splenic lymphangioma
splenic metastases
Splenic rupture
Splenomegaly
splenopancreasectomy
Spontaneous internal jugu
Squamous cell carcinoma
squamous cell carcinoma a
squamous cell carcinoma o
Squamous cell carcinoma,V
Squamous cell laryngeal c
stage
stage III
Staging
Standard incidence ratio
statistical method.
Statistical model
Stealth liposomes
stem cell transplantation
stenosis
Stereotactic
stereotactic body radiati
stereotactic radiosurgery
Sternberg tumor
Sternum
Steroid receptors
Steroids
Stevens-Johnson syndrome
Stomach
stomach cancer
stool test
stop-flow
Subcutaneous mastectomy
subdural hematoma
Subdural osteomas
Subgroup analysis
Sugar industry
Suicide
Suicide thoughts
sulfur compounds
Sunburn
sunitinib
Superficial therapy
Superior hypogastric plex
superior mediastinal synd
superior vena cava syndro
supernumerary breast
Superoxide dismutase
supraclavicular adenopath
supraclavicular lymphaden
supraclavicular radiother
supraventricular tachycar
Surgery
surgical complications
Surgical margins
surgical mortality
surgical oncology
surgical procedures
Surgical resection
surgical strategy
surgical treatment
Suriname
Survey
Survival
Survival analysis
SV40
Swiss albino mice
Sympathetic cervical chai
Sympathetic chain
Symporter (NIS)
Symptom management
symptom-to-treatment inte
Symptoms
Synaptophysin
synchronous cancer
Synchronous multicentric
Synchronous presentation
synchronous triple cancer
Synchronous tumors
synergistic effect
synovial sarcoma
systemic chemotherapy
T2 signal intensity
Tamoxifen
Tangential irradiation
tanshinone II-A
target coverage
Target delineation
target therapies
target therapy
Target volume
targeted contrast materia
targeted drug delivery
targeting
taxane
Taxol
Taxotere
TCF regimen
tcr-gamma
Technetium-99m
technique investigation
tectal glioma
telemedicine
Telomerase activity
telomerase RNA
Temozolomide
temozolomide refractory
teratoma
terebrant ulcer
terminal cancer patients
terminal patient
terminally ill
test
testicular cancer
Testicular seminoma
Testicular tumors
Testis
Testosterone,Wistar rats
tetrandrine
thalidomide
Therapeutic guidelines
therapeutic strategies
therapy
therapy-related leukemia
thiamine
Thiols
third-line chemotherapy
Three-dimensional conform
three-dimensional conform
Thrombocytopenia
thrombophilic screening
Thrombosis
Thrombotic thrombocytopen
Thymic carcinoid
thymolipoma
Thymoma
thymus
Thyroglobulin
Thyroglobulin (Tg)
Thyroglossal duct cyst
Thyroglossal duct remnant
Thyroid
Thyroid cancer
Thyroid cancer scintigrap
Thyroid carcinoma
thyroid gland
thyroid lesions
thyroid metastases
thyroid metastasis
Thyroid neoplasms
thyroid nodule
thyroid squamous cell car
thyroid surgery
thyroid tumor
thyroidectomy
time trends
Time-intensity dynamic pr
TIMP3
Tissue remodelling
tobacco
Tobacco smoking
tomotherapy
Tongue
tongue cancer
tonsil
tonsil metastasis
topoisomerase IIa
total colectomy
Total dermatoscopic score
total gastrectomy
total parental nutrition
Toxicity
TP53
TPS commissioning
TRAIL
training
tram
transanal excision
Transarterial chemoemboli
transcatheter arterial ch
Transitional cell carcino
translational research
Transplant-related compli
Transrectal ultrasonograp
transverse colon
trastuzumab
Treatment
Treatment guidelines
treatment monitoring
treatment response predic
treatment verification
Trends
trends in smoking
TRIMprobTM
Triphenylethylenes
triplet
triplet regimen
Trisomy 21
TSPAN1
TTF-1
Tuberculosis
Tumor
tumor and nontumor lesion
tumor bank
tumor burden
tumor cells
Tumor lysis syndrome
Tumor marker
Tumor marker CA 15-3
Tumor markers
tumor metastasis
tumor response
tumor sample
tumor seeding
tumor size
tumor stage
Tumor staging
Tumor-associated mononucl
Tumor-like lesion
tumor-like multiple scler
Tumorigenesis
Tumorlets
Tumors macrophages
Turkish breast cancer sur
tuscany
twins
type-1 neurofibromatosis
Tyrosine kinase
tyrosine kinase inhibitor
ultrasonography
Ultrasound
Ultrasound-guided fine-ne
Umbilical nodule
unconventional cancer tre
undertreatment
undifferentiated esophage
undifferentiated nasophar
uniscale assessment
unknown primary
unknown primary site
unknown primary tumors
unresectable
Unusual metastatic sites
uPA,TIMP
upper aerodigestive cance
Upregulation
Urachal carcinoma
Urbanization
urethane
Urinary bladder metastase
urinary tract
urokinase plasminogen act
urothelial cancer
Urothelial carcinoma
Urothelial carcinoma of t
urothelium.
usage of cam
uterine cervical cancer
uterine cervix cancer
uterine cervix carcinoma
uterine metastasis
Uterine neoplasms
Uterine sarcoma
uterine serous cancer
Uterus
Uveal melanoma
UW-QOL
Vaccination
Vacuum-assisted core biop
Vaginal cancer
validation
validity
Vascular endothelial grow
vascular proliferation
Vascular tumor
vascular tumors
VE-cadherin,VEGF
vectorization
Venous thromboembolic com
Vertebral compression fra
Vertebral tumor
vertebroplasty
videoconference
Vinblastine
Vinorelbine
virtual bio repository
vitamin A
Vitamin D analogs
VM26
vocal fold paralysis
vocal folds
voice disorder
VP3
Weekly administration
Weekly docetaxel
weekly docetaxel and gemc
Weekly paclitaxel therapy
Weekly therapy
Wernicke's encephalopath
WHO histopathological cla
whole abdominal irradiati
whole brain radiotherapy
wnt signaling
Wnt-5a
women
Woringer-Kolopp disease
X-ray computed tomography
X-rays
Xenograft
yolk sac tumor
young
youth smoking
yttrium-90
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