Technology in Cancer Research and Treatment
SCIE-ISI SCOPUS (2002-2023)
1533-0338
1533-0346
Mỹ
Cơ quản chủ quản: SAGE Publications Inc.
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Photodynamic therapy (PDT) has received increased attention since the regulatory approvals have been granted to several photosensitizing drugs and light applicators worldwide. Much progress has been seen in basic sciences and clinical photodynamics in recent years. This review will focus on new developments of clinical investigation and discuss the usefulness of various forms of PDT techniques for curative or palliative treatment of malignant and non-malignant diseases.
There is a clear dose response for localized prostate cancer radiotherapy and there probably is a radiobiological rationale for hypo-fractionation. Combining the two should maximize tumor control and increase the therapeutic ratio. This study examines the rationale and technical feasibility of CyberKnife radiotherapy (a robotic arm-driven linear accelerator) for localized prostate cancer. Its ability to deliver non-coplanar non-isocentric arcs can yield maximally conformal isodoses. It is the only integrated system capable of target position verification and real-time tracking during delivery of conformal stereotactic radiotherapy.
Inverse planning with the CyberKnife is used to design a course of radiotherapy for localized prostate cancer. Fiducial markers within the gland are used to verify organ position and track organ motion via an orthogonal pair of electronic x-ray imaging devices and provide real-time feedback correction to the robotic arm during delivery. Conformal isodose curves and dose volume histograms (DVH) are used to compare with an optimized Intensity-Modulated Radiotherapy (IMRT) plan actually delivered to the study patient based upon CT scan-derived organ volumes.
The CyberKnife can produce superior DVHs for sparing of rectum and bladder and excellent DVHs for target coverage compared with IMRT, and possesses dose heterogeneities to the same degree as IMRT plans. Because of the significantly longer delivery times required it would be best suited for hypo-fractionated regimens. Such dose regimens might allow for biologically equivalent dose escalation without increased normal tissue toxicity. Since the CyberKnife can verify organ position and motion and correct for this in real-time it is the ideal means of achieving such excellent DVHs without a compromise in doses to normal tissues. These capabilities are essential if one contemplates hypo-fractionated regimens with large dose-per-fraction sizes (>5Gy to 10Gy) and dose-escalation.
Here we report results from the first cohort of over 100 patients treated with hypofractionated, stereotactic body radiotherapy (SBRT) for early stage prostate cancer. Between February 2005 and December 2006, 112 patients with localized, biopsy-proven adenocarcinoma of the prostate (clinical stage T1cN0M0 to T2cN0M0) were treated in Naples, FL on a CyberKnife system (Accuray Incorporated, Sunnyvale, CA). Eighty-one patients had a Gleason score of 3+3. Mean initial PSA was 6.0, and mean initial prostate volume was 46.3cc. Implanted gold fiducials were used for image-guided targeting and tracking. Patients received 35–36 Gy administered in 5 consecutive fractions to the prostate and the proximal seminal vesicles, as identified on CT and MRI scans. At a median follow-up of 24 months, the mean PSA value was 0.78 ng/ml. Two patients have developed biopsy-confirmed local relapse; one developed distant metastases. Acute side effects were generally mild and resolved shortly after treatment. A single Grade 3 rectal complication was reported (bleeding). Eighty-two percent of patients who were sexually potent before treatment maintained erectile function post-treatment. Additional follow-up is required to better evaluate potential late toxicity and long-term PSA outcomes.
The use of external surrogates to predict tumor motion in real-time for extra-cranial sites requires the use of accurate correlation models. This is extremely challenging when motion prediction is to be performed over several breathing cycles, as occurs for realtime tumor tracking with Cyberknife® Synchrony®. In this work we compare three different approaches to infer tumor motion based on external surrogates, since no comparative study is available to assess the accuracy of correlation models in tumor tracking over a long time period. We selected 20 cases in a database of 130 patients treated with realtime tumor tracking by means of the Synchrony® module. The implemented correlation models comprise linear/quadratic correlation, artificial neural networks and fuzzy logic. The accuracy of each correlation model is evaluated on the basis of ground truth tumor position information acquired during treatment, as detected by means of stereoscopic X-ray imaging. Results show that the implemented models achieve an error reduction with respect to Synchrony®, measured at the 95% confidence level, up to 10.8% for the fuzzy logic approach. This latter is able to partly reduce the incidence of tumor tracking errors above 6 mm, resulting in improved accuracy for larger discrepancies. In conclusion, complex models are suggested to predict tumor motion over long time periods. This leads to an effective improvement with respect to Cyberknife® Synchrony®. Future studies will investigate the sensitivity of the implemented models to the input database, in order to define optimal strategies.
Stereotactic body radiotherapy (SBRT) is a new treatment modality for prostate cancer. The current study evaluates CyberKnife® SBRT and reports toxicity and early Prostate-Specific Antigen (PSA) kinetics. From June 2006 to August 2009, 45 low-and intermediate-risk prostate cancer patients received Cyberknife SBRT of 35 Gy in five fractions with 95% minimum target coverage. Median follow-up was 20-months (range 6–42-months). Seventeen patients received androgen-deprivation therapy also. Acute complications were mild, short-lived and no greater than Grade 2 by RTOG scale. Late toxicities consisted of one patient (2.2%) experiencing Grade 2 rectal, one patient (2.2%) Grade 3 and four patients (8.8%) with Grade 1 urinary toxicity. PSA in all patients progressively declined from a mean 4.7 ng/ml baseline to 1.48 ng/ml at three months, to 0.68 ng/ml at 12 months and to 0, 35 ng/ml at 24 months. The 28 hormon-naive patients had the mean PSA value of 1.1 ng/ml at one year from a mean 6.65 ng/ml baseline. There was a significant PSA value reduction in 11 hormone therapy patients with low baseline PSA value (< 1 ng/ml) from 0.37 down 0.14 ng/ml (p value 0.0068) at one year. Moreover, 14 low risk patients gave better results of mean PSA value than 17 Intermediate risk patients 0.43 ng/ml vs. 0.93 ng/ml (p value 0.02) at one year. No patient had biochemical failure at last follow-up. Hypofractionated SBRT appears to have potential against prostate cancer. Low toxicity and encouraging biochemical control support its use in early-stage prostate cancer. Results encourage further follow-up and larger studies.
Patients receiving stereotactic body radiotherapy for stage I non-small cell lung cancer are typically staged clinically with positron emission tomography–computed tomography. Currently, limited data exist for the detection of occult hilar/peribronchial (N1) disease. We hypothesize that positron emission tomography–computed tomography underestimates spread of cancer to N1 lymph nodes and that future stereotactic body radiotherapy patients may benefit from increased pathologic evaluation of N1 nodal stations in addition to N2 nodes.
A retrospective study was performed of all patients with clinical stage I (T1-2aN0) non-small cell lung cancer (American Joint Committee on Cancer, 7th edition) by positron emission tomography–computed tomography at our institution from 2003 to 2011, with subsequent surgical resection and lymph node staging. Findings on positron emission tomography–computed tomography were compared to pathologic nodal involvement to determine the negative predictive value of positron emission tomography–computed tomography for the detection of N1 nodal disease. An analysis was conducted to identify predictors of occult spread.
A total of 105 patients with clinical stage I non-small cell lung cancer were included in this study, of which 8 (7.6%) patients were found to have occult N1 metastasis on pathologic review yielding a negative predictive value for N1 disease of 92.4%. No patients had occult mediastinal nodes. The negative predictive value for positron emission tomography–computed tomography in patients with clinical stage T1 versus T2 tumors was 72 (96%) of 75 versus 25 (83%) of 30, respectively ( P = .03), and for peripheral versus central tumor location was 77 (98%) of 78 versus 20 (74%) of 27, respectively ( P = .0001). The negative predictive values for peripheral T1 and T2 tumors were 98% and 100%, respectively; while for central T1 and T2 tumors, the rates were 85% and 64%, respectively. Occult lymph node involvement was not associated with primary tumor maximum standard uptake value, histology, grade, or interval between positron emission tomography–computed tomography and surgery.
Our results support pathologic assessment of N1 lymph nodes in patients with stage Inon-small cell lung cancer considered for stereotactic body radiotherapy, with the greatest benefit in patients with central and T2 tumors. Diagnostic evaluation with endoscopic bronchial ultrasound should be considered in the evaluation of stereotactic body radiotherapy candidates.
Colorectal cancer is one of the most common cancers worldwide in terms of both incidence and mortality. The associations of expressions of tissue and plasma miR-29b were not detected in this study.
There are 400 healthy age- and gender-matched controls enrolled in this study in a rate of 1:2. The receiver operating characteristic curve analysis was undertaken using the expression level for miR-29b in the colorectal cancer specimens from patients with cancer and healthy controls to assess the diagnostic accuracy of both tissue and plasma miR-29b levels.
It was found that the expression of plasma miR-29b is associated with the tissue miR-29b. Advanced study showed that aberrant miR-29b expression in both cancer tissues and plasma is associated with the clinicopathological data of patients with colorectal cancer. Tissue miR-29b showed an AUC of 0.883, with a sensitivity of 81.6% and a specificity of 84.9%. However, the AUC for plasma miR-29b was 0.743, with a sensitivity of 61.4% and a specificity of 72.5%. The analyses of the biological effects of miR-29b for colorectal cancer showed that miR-29b could inhibit the cell viability and migration.
In summary, our data suggest that both the tissue and the plasma miR-29b levels have some value as a diagnostic tool for colorectal cancer. Advanced biological effects were conducted to detect the potential effect on the cell viability and migration. Future investigations including larger patient populations and patients with early-stage colorectal cancer are needed to confirm the potential diagnostic value of miRNA-29b in colorectal cancer.
The purpose of this study was to evaluate the characterization of a new cationic vector. Low generation polypropylenimine (DAB-8) was conjugated to β-cyclodextrin (β-CyD), and the chemical characters of the vector were investigated and confirmed by 1 H NMR, FT-IR, TGA, TEM, particle size, and zeta potential assay. The biological property was identified by MTT assay and gene transfer efficiency was performed in cell lines. The results showed that the new vector had low cytotoxicity and high transfection efficiency in vitro. This suggested that β-CyD-DAB-8 has a potential ability to act as a non-viral vector in gene delivery.
Microfibril-associated protein 2 (MFAP2) is an extracellular matrix protein that regulates the function of microfibrils by interacting with fibrillin. MFAP2 has been reported to play an important role in metabolic diseases and has been shown to be significantly overexpressed in head and neck squamous cell carcinoma and Hepatocellular carcinoma (HCC). However, the molecular function and prognostic value of MFAP2 have never been reported in HCC or other tumors.
In the present study, expression characteristics of MFAP2 in HCC, its influence on the development of HCC, as well as its function and potential mechanism in HCC were verified by Quantitative reverse transcription-polymerase chain reaction, bioinformatics data mining and in vitro cell experiments.
MFAP2 was prominently high-expressed in HCC and associated with cancer stages. HCC patients with higher MFAP2 expression displayed lower overall survival (OS) and disease-specific survival(DSS), while there was no significant difference in recurrence-free survival (RFS). In vitro experiments showed that downregulation of MFAP2 inhibited proliferation, migration level of HCC cells. Transcription factors, DNA methyltransferases, immune factors may interact with MFAP2 mRNA to promote tumor progression in HCC.
These findings suggest that MFAP2 may play a key role in the development of HCC. Therefore, MFAP2 may be a valuable prognostic marker and an effective anticancer target in HCC.
This study aims to reveal early breast cancer (BC) specific competing endogenous RNA (ceRNA) network through the expression profiles of microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and mRNAs.
Based on The Cancer Genome Atlas (TCGA), we obtained the differentially expressed mRNAs, miRNAs, and lncRNAs (DEmRNAs, DEmiRNAs and DElncRNAs) between early BC and normal samples. The lncRNA–miRNA–mRNA interaction network was constructed using Cytoscape. Functional enrichment were performed using GeneCoDis3. The expression of selected genes were validated by qRT-PCR. Based on the published dataset, we validated the result of TCGA integration analysis. The diagnostic and prognostic value of candidate genes was evaluated by ROC curve analysis and survival analysis, respectively.
Totally, 1207 DEmRNAs, 194 DElncRNAs and 37 DEmiRNAs were obtained. Functional enrichment analysis results showed that all of DEmRNAs were enriched in pathway of cytokine-cytokine receptor interaction, PPAR signaling pathway and pathways in cancer. The DEmRNA-DEmiRNA-DElncRNA interaction network in early BC was consisted of 23 DEmiRNAs, 95 DElncRNAs and 309 DEmRNAs. Among ceRNA network, IL-6-hsa-miR-182-5p-ADAMTS9-AS1 interactions, LIFR-hsa-miR-21-5p-ADAMTS9-AS1 interactions and MMP1/MMP11-hsa-miR-145-5p-CDKN2B-AS1 interactions were speculated to involve in the development of early BC. The qRT-PCR results were consistent with our integrated analysis. Except for ADAMTS9-AS1 and CDKN2B-AS1, expression of the others results in the Gene Expression Omnibus (GEO) dataset were generally consistent with TCGA integrated analysis. The area under curve (AUC) of the ADAMTS9-AS1, CDKN2B-AS1, IL-6, MMP11, hsa-miR-145-5p and hsa-miR-182-5p were 0.947, 0.862, 0.842, 0.993, 0.960 and 0.944, and the specificity and sensitivity of the 6 biomarkers were 83.4% and 95.6%, 72.2% and 90.3%, 80.1% and 74.3%, 96.2% and 96.5%, 90.1% and 92.3%, and 88.7% and 90.4%, respectively. In addition, IL-6 had potential prognostic value for early BC.
These findings may provide novel insights into the lncRNA-miRNA-mRNA network and uncover potential therapeutic targets in early BC.