Technology in cancer research & treatment (Technol Cancer Res Treat)

Publications in this journal

• Article: Hypofractionated Stereotactic Radiotherapy in Five Daily Fractions for Post-Operative Surgical Cavities in Brain Metastases Patients With and Without Prior Whole Brain Radiation.

  A Al-Omair, H Soliman, W Xu, A Karotki, T Mainprize, N Phan, S Das, J Keith, R Yeung, J Perry, M Tsao, A Sahgal
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  ABSTRACT: Our purpose was to report efficacy of hypofractionated cavity stereotactic radiotherapy (HCSRT) in patients with and without prior whole brain radiotherapy (WBRT). 32 surgical cavities in 30 patients (20 patients/21 cavities had no prior WBRT and 10 patients/11 cavities had prior WBRT) were treated with image-guided linac stereotactic radiotherapy. 7 of the 10 prior WBRT patients had "resistant" local disease given prior surgery, post-operative WBRT and a re-operation, followed by salvage HCSRT. The clinical target volume was the post-surgical cavity, and a 2-mm margin applied as planning target volume. The median total dose was 30 Gy (range: 25-37.5 Gy) in 5 fractions. In the no prior and prior WBRT cohorts, the median follow-up was 9.7 months (range: 3.0-23.6) and 15.3 months (range: 2.9-39.7), the median survival was 23.6 months and 39.7 months, and the 1-year cavity local recurrence progression- free survival (LRFS) was 79 and 100%, respectively. At 18 months the LRFS dropped to 29% in the prior WBRT cohort. Grade 3 radiation necrosis occurred in 3 prior WBRT patients. We report favorable outcomes with HCSRT, and well selected patients with prior WBRT and "resistant" disease may have an extended survival favoring aggressive salvage HCSRT at a moderate risk of radiation necrosis.
  Technology in cancer research & treatment 04/2013;
• Article: Inverse Planning Optimization Method for Intensity Modulated Radiation Therapy.

  Y Lan, H Ren, C Li, Z Min, J Wan, J Ma, C-C Hung
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  ABSTRACT: In order to facilitate the leaf sequencing process in intensity modulated radiation therapy (IMRT), and design of a practical leaf sequencing algorithm, it is an important issue to smooth the planned fluence maps. The objective is to achieve both high-efficiency and high-precision dose delivering by considering characteristics of leaf sequencing process. The key factor which affects total number of monitor units for the leaf sequencing optimization process is the max flow value of the digraph which formulated from the fluence maps. Therefore, we believe that one strategy for compromising dose conformity and total number of monitor units in dose delivery is to balance the dose distribution function and the max flow value mentioned above. However, there are too many paths in the digraph, and we don't know the flow value of which path is the maximum. The maximum flow value among the horizontal paths was selected and used in the objective function of the fluence map optimization to formulate the model. The model is a traditional linear constrained quadratic optimization model which can be solved by interior point method easily. We believe that the smoothed maps from this model are more suitable for leaf sequencing optimization process than other smoothing models. A clinical head-neck case and a prostate case were tested and compared using our proposed model and the smoothing model which is based on the minimization of total variance. The optimization results with the same level of total number of monitor units (TNMU) show that the fluence maps obtained from our model have much better dose performance for the target/non-target region than the maps from total variance based on the smoothing model. This indicates that our model achieves better dose distribution when the algorithm suppresses the TNMU at the same level. Although we have just used the max flow value of the horizontal paths in the diagraph in the objective function, a good balance has been achieved between the dose conformity and the total number of monitor units. This idea can be extended to other fluence map optimization model, and we believe it can also achieve good performance.
  Technology in cancer research & treatment 04/2013;
• Article: Inhibition of Glucose Transporter 1 (GLUT1) Chemosensitized Head and Neck Cancer Cells to Cisplatin.

  Y-D Wang, S-J Li, J-X Liao
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  ABSTRACT: Glucose transporter 1 (GLUT1) facilitates the cellular uptake of glucose and is overexpressed in most cancers. The altered expression of GLUT1 may influence the sensitivity of tumor cells to chemotherapy. This study investigated whether the knockdown of GLUT1 expression to sensitize head and neck cancer cells to the chemotherapy drug cisplatin in vitro. Anti-GLUT1 antibody was used to block activity of GLUT1 protein, and GLUT1-shRNA was used to knock down its mRNA expression in Cal27 cells. Immunocytochemistry, Western blot, and qRT-PCR were used to detect expression of GLUT1 mRNA and protein, respectively. Lentivirus was used to carrying GLUT1-shRNA to knockdown GLUT1 expression in Cal27 cells for MTT and flow cytometry analyses of cell viability and apoptosis, respectively. Glucose uptake assay was used to assess the changes in glucose levels in Cal27 cells. It showed that GLUT1 mRNA and protein were expressed in Cal27 cells, and GLUT1 protein was localized on the cell membrane. Both anti-GLUT1 antibody and GLUT1-shRNA sensitized Cal27 cells to cisplatin treatment under both normoxia and hypoxia conditions. Anti- GLUT1 antibody and GLUT1-shRNA inhibited tumor cell growth in vitro and induced them to undergo apoptosis. GLUT1-shRNA also suppressed tumor cell uptake of glucose into the cells. Our findings suggest that inhibition of GLUT1 activity and expression can sensitize Cal27 cells to cisplatin treatment in both normoxic and hypoxic conditions. These data could be further verified in animal xenografts before potential application as a clinical adjuvant or neoadjuvant therapy of head and neck cancer with cisplatin.
  Technology in cancer research & treatment 04/2013;
• Article: Predictive Effect of XPA and XPD Polymorphisms on Survival of Advanced NSCLC Patients Treated with Platinum-based Chemotherapy: A Three-dimensional (3-D), Polyacrylamide Gel-Based DNA Microarray Method.

  H Cheng, Q Qin, X Sun, F Li, N Sun, L Cheng, Z Lu, B Chen
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  ABSTRACT: Platinum-based chemotherapy is a primary treatment for patients with advanced non-small cell lung cancer (NSCLC). Considering individual differences, an effective and convenient method is urgently needed to identify the sensitivity of individual patient to platinum based regimen. Genetic variants in DNA repair genes are presumed to represent important determinants of drug efficacy. Our previous studies have demonstrated the involvement of xeroderma pigmentosum group A (XPA) codon23 and xeroderma pigmentosum group D (XPD) codon751 single-nucleotide polymorphisms (SNPs) in clinical response to platinum based chemotherapy in advanced NSCLC patients. Thus, a follow-up study was carried out to investigate the relevance of these genotypes and survival of the cohort (n = 115). The three-dimensional (3-D), polyacrylamide gel-based DNA microarray method was used to assess the genotypes of XPA and XPD in peripheral lymphocytes. Log-rank test revealed that the variant genotypes of XPA23 (A/G+G/G) were associated with significantly longer progression- free survival (PFS) (6.0 m vs. 10.6 m, log-rank P = 0.001) and overall survival (OS) (11.2 m vs. 20.8 m, log-rank P = 0.001). In Cox proportional hazards model, the hazard ratio (HR) for death in patients with G allele was 0.65 (P = 0.049). While no significant differences were observed in PFS or OS according to XPD Lys751Gln genotypes (log-rank P > 0.05). In combination with our previous short-term clinical results, this study further confirmed that by detecting the SNPs in blood cells, XPA A23G polymorphic variants might be a promising biomarker in predicting a favor prognosis of NSCLC patients and be helpful towards designing individualized treatments.
  Technology in cancer research & treatment 04/2013;
• Article: The Potential for an Enhanced Role For MRI in Radiation-therapy Treatment Planning.

  P Metcalfe, G P Liney, L Holloway, A Walker, M Barton, G P Delaney, S Vinod, W Tome
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  ABSTRACT: The exquisite soft-tissue contrast of magnetic resonance imaging (MRI) has meant that the technique is having an increasing role in contouring the gross tumor volume (GTV) and organs at risk (OAR) in radiation therapy treatment planning systems (TPS). MRI-planning scans from diagnostic MRI scanners are currently incorporated into the planning process by being registered to CT data. The soft-tissue data from the MRI provides target outline guidance and the CT provides a solid geometric and electron density map for accurate dose calculation on the TPS computer. There is increasing interest in MRI machine placement in radiotherapy clinics as an adjunct to CT simulators. Most vendors now offer 70 cm bores with flat couch inserts and specialised RF coil designs. We would refer to these devices as MR-simulators. There is also research into the future application of MR-simulators independent of CT and as in-room image-guidance devices. It is within the background of this increased interest in the utility of MRI in radiotherapy treatment planning that this paper is couched. The paper outlines publications that deal with standard MRI sequences used in current clinical practice. It then discusses the potential for using processed functional diffusion maps (fDM) derived from diffusion weighted image sequences in tracking tumor activity and tumor recurrence. Next, this paper reviews publications that describe the use of MRI in patient-management applications that may, in turn, be relevant to radiotherapy treatment planning. The review briefly discusses the concepts behind functional techniques such as dynamic contrast enhanced (DCE), diffusion-weighted (DW) MRI sequences and magnetic resonance spectroscopic imaging (MRSI). Significant applications of MR are discussed in terms of the following treatment sites: brain, head and neck, breast, lung, prostate and cervix. While not yet routine, the use of apparent diffusion coefficient (ADC) map analysis indicates an exciting future application for functional MRI. Although DW-MRI has not yet been routinely used in boost adaptive techniques, it is being assessed in cohort studies for sub-volume boosting in prostate tumors.
  Technology in cancer research & treatment 04/2013;
• Article: IMRT or 3D-CRT in Glioblastoma? A Dosimetric Criterion for Patient Selection.

  S Lorentini, D Amelio, M G Giri, F Fellin, G Meliado, A Rizzotti, M Amichetti, M Schwarz
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  ABSTRACT: Intensity modulated radiation therapy (IMRT) is increasingly employed in glioblastoma (GBM) treatment. The present work aimed to assess which clinical-dosimetric scenario could benefit the most from IMRT application, with respect to three-dimensional conformal radiation therapy (3D-CRT). The number of organs at risk (OARs) overlapping the planning target volume (PTV) was the parameter describing the clinical-dosimetric pattern. Based on the results, a dosimetric decision criterion to select the most appropriate treatment technique is provided. Seventeen previously irradiated patients were retrieved and re-planned with both 3D-CRT and IMRT. The prescribed dose was 60 Gy/30fx. The cases were divided into 4 groups (4 patients in each group). Each group represents the scenario where 0, 1, 2 or 3 OARs overlapped the target volume, respectively. Furthermore, in one case, 4 OARs overlapped the PTV. The techniques were compared also in terms of irradiated healthy brain tissue. The results were evaluated by paired t-test. IMRT always provided better target coverage (V95%) than 3D-CRT, regardless the clinical-dosimetric scenario: difference ranged from 0.82% (p = 0.4) for scenario 0 to 7.8% (p = 0.02) for scenario 3, passing through 2.54% (p = 0.18) and 5.93% (p = 0.08) for scenario 1 and 2, respectively. IMRT and 3D-CRT achieved comparable results in terms of dose homogeneity and conformity. Concerning the irradiation of serial-kind OARs, both techniques provided nearly identical results. A statistically significant dose reduction to the healthy brain in favor of IMRT was scored. IMRT seems a superior technique compared to 3D-CRT when there are multiple overlaps between OAR and PTV. In this scenario, IMRT allows for a better target coverage while maintaining equivalent OARs sparing and reducing healthy brain irradiation. The results from our patients dataset suggests that the overlap of three OARs can be used as a dosimetric criterion to select which patients should receive IMRT treatment.
  Technology in cancer research & treatment 04/2013;
• Article: Segment Edit and Segment Weight Optimization: Two Techniques for Intensity Modulated Radiation Therapy and Their Application to the Planning for Nasopharyngeal Carcinoma.

  Q Li, H Pei, J Mu, Q Hu, W Gu
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  ABSTRACT: The purpose of this study was to evaluate the two functions: segment weight optimization (SWO) and segment edit (SE) in the latest XiO 4.7 radiation treatment planning system and their effect on the planning of intensity modulated radiation therapy (IMRT) for Nasopharyngeal Carcinoma (NPC). SWO first appeared in XiO 4.5 and SE in XiO 4.7. Twelve patients with NPC were selected and there were three plans for each patient: the common step-and-shoot IMRT plan (C-IMRT); S-IMRT was based on the result of C-IMRT and the plan was further optimized with SWO; F-IMRT was based on S-IMRT and the segments were edited for lowering the dose received by normal tissues. The paired plans were analyzed by comparing the total number of segments, monitor units, the homogeneity index and conformity index of the target volumes and the dose delivered to organs at risk (OAR) including spinal cord, brain stem, optic nerves, chiasm, parotids and larynx. The study exhibited that the total number of segments and monitor units of S-IMRT and F-IMRT were around 25.3%, 3.4% less than those of C-IMRT respectively. The HI and CI indexes of target volumes among three kinds of plans did not show the significant difference. The doses received by spinal cord, brain stem, parotids, larynx were decreased at S-IMRT and F-IMRT as compared to C-IMRT; the highest doses delivered to chiasm and optic nerves were S-IMRT, the next C-IMRT, the lowest F-IMRT. This study showed that the SWO function could substantially reduce the total number of segments of step-and-shoot IMRT plans and the SE function had the incredible ability to lower the dose received by normal tissues.
  Technology in cancer research & treatment 04/2013;
• Article: Stereotactic Body Radiotherapy: Volumetric Modulated Arc Therapy Versus 3D Non-coplanar Conformal Radiotherapy for the Treatment of Early Stage Lung Cancer.

  C Herbert, W Kwa, S Nakano, K James, V Moiseenko, J Wu, D Schellenberg, M Liu
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  ABSTRACT: Stereotactic body radiotherapy (SBRT) is a treatment option for patients with early stage lung cancer. Treatment duration can be >30 minutes per fraction with non-coplanar 3D-conformal radiotherapy (3D-CRT). Whilst this is generally well tolerated, faster delivery techniques are desirable. Volumetric modulated arc therapy (VMAT) allows for fast delivery of radiation treatment. The purpose of this planning study was to compare SBRT with 3D-CRT and VMAT, with VMAT plans generated using both single arc and 3 non-coplanar partial arcs. Ten patients who previously underwent SBRT (48 Gy in 4 fractions) with 3D-CRT were selected. VMAT plans were generated to treat the PTV while limiting doses to organs at risk. Cumulative dose volume histogram (DVH) parameters were compared between the 3 techniques using the Wilcoxon matched pairs test. Treatment delivery time was also assessed. Both VMAT techniques covered target volumes more conformally than 3D-CRT with a mean V48/VPTV of 1.21 for 3D-CRT, 1.03 for 3 arc plans and 1.01 for single arc plans (p = 0.005). Dose constraints to organs at risk were met using all three techniques. Mean lung doses were 2.93 Gy for 3D-CRT, 2.87 Gy for single arc and 2.73 Gy for the 3 arc technique (3-arc vs. 3D-CRT: p = 0.009). Lung V20 for 3D-CRT, 1 arc and 3 arcs were 3.24%, 2.89% and 2.73%, respectively (3 arc vs. 3D-CRT: p 5 0.028). Mean time to deliver a single fraction was 13 minutes for 3D-CRT, 9.2 minutes for 3 arcs and 5.5 minutes for 1 arc. VMAT resulted in improved conformality compared to 3D-CRT. The 3 arc technique appears to have the lowest dose to lung although the magnitude is unlikely to be clinically significant. The main advantage of VMAT over 3D-CRT is faster treatment delivery time. Shortened treatment times are anticipated to improve tolerability of this treatment and reduce the chance of error due to intra-fraction motion.
  Technology in cancer research & treatment 04/2013;
• Article: Drug Embedded PVP Coated Magnetic Nanoparticles for Targeted Killing of Breast Cancer Cells.

  P A Rose, P K Praseetha, M Bhagat, P Alexander, S Abdeen, M Chavali
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  ABSTRACT: Magnetic drug targeting is a drug delivery system that can be used in loco-regional cancer treatment. Coated magnetic particles, called carriers, are very useful for delivering chemotherapeutic drugs. Magnetic carriers were synthesized by co-precipitation of iron oxide followed by coating with polyvinyl pyrrolidone (PVP). Characterization was performed using X-ray diffraction, TEM, TGA, FTIR and UV-Vis Spectroscopy. Magnetite (Fe3O4) remained as the core of the carrier. The amount of PVP bound to the iron oxide nanoparticles was estimated by thermogravimetric analysis (TGA) and the attachment of PVP to the iron oxide nanoparticles confirmed by FTIR analysis. The loading efficiency of Epirubicin hydrochloride onto the PVP coated and uncoated iron oxide nanoparticles was measured at intervals such as 1 hr and 24 hrs by UV-Vis Spectroscopy. The binding of Epirubicin hydrochloride to the PVP coated and uncoated iron oxide nanoparticles were confirmed by FTIR analysis. The present findings showed that Epirubicin hydrochloride loaded PVP coated iron oxide nanoparticles are promising for magnetically targeted drug delivery. The drug displayed increased cell cytotoxicity at lower concentrations when conjugated with the nanoparticles than being administered conventionally as individual drugs.
  Technology in cancer research & treatment 03/2013;
• Article: Optical Spectral Fingerprints of Tissues from Patients with Different Breast Cancer Histologies Using a Novel Fluorescence Spectroscopic Device.

  L A Sordillo, Y Pu, P P Sordillo, Y Budansky, R R Alfano
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  ABSTRACT: The fluorescence of paired human breast malignant and normal tissue samples was investigated using a novel fluorescence spectroscopic (S3-LED) ratiometer unit with no moving parts. This device can measure the emission spectra of key native organic biomolecules such as tryptophan, tyrosine, collagen and elastin within tissues by using LED (light emitting diode) excitation sources coupled to an optical fiber. With this device, the spectral profiles of 11 paired breast cancerous and normal samples from 11 patients with breast carcinoma were obtained. In each of the 11 cases, marked increases in the tryptophan levels were found in the breast carcinoma samples when compared to the normal breast tissues. In the breast cancer samples, there were also consistently higher ratios of the 340 to 440 nm and the 340 to 460 nm intensity peaks after 280 nm excitation, likely representing an increased tryptophan to NADH ratio in the breast cancer samples. This difference was seen in the spectral profiles of the breast cancer patients regardless of whether they were HER2 positive or negative or hormone receptor positive or negative, and was found regardless of menopausal status, histology, stage, or tumor grade.
  Technology in cancer research & treatment 03/2013;
• Article: Can a Belly Board Reduce Respiratory-induced Prostate Motion in the Prone Position? - Assessed by Cine-magnetic Resonance Imaging.

  K Terashima, K Nakamura, Y Shioyama, T Sasaki, S Ohga, T Nonoshita, T Yoshitake, K Atsumi, K Asai, M Hirakawa, S Anai, H Yoshikawa, H Honda
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  ABSTRACT: The purpose of this study is to evaluate the real-time respiratory motion of the prostate and surrounding tissues/organs in the supine and prone positions and to investigate, using cine-MRI, whether a belly board can reduce respiratory-induced motion in the prone position. Cine-MRI scans were made of 13 volunteers in the supine and prone positions on a flat board and in two different prone positions using a belly board. Images in cine mode were recorded for 20 seconds. For each session, the points of interest (POIs) were located at the apex, base, mid-anterior surface and mid-posterior surface of the prostate; the tip of the seminal vesicle; the pubic symphysis; and the sacrum. The maximum range and standard deviation (SD) of the displacement from the mean value were calculated. The SDs for each of the four different positions were compared using a paired t-test. Respiratory-induced prostate motion was significantly larger in the prone position than in the supine position. However, when a belly board was used in the prone position, motion in the prostate and surrounding tissues/organs was significantly reduced. There were no significant differences between the two different positions using a belly board in any of the POIs.
  Technology in cancer research & treatment 03/2013;
• Article: Acute Hematologic and Mucosal Toxicities in Head and Neck Cancer Patients Undergoing Chemoradiotherapy: A Comparison of 3D-CRT, IMRT, and Helical Tomotherapy.

  T J Kruser, S R Rice, K P Cleary, H M Geye, W A Tome, P M Harari, K R Kozak
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  ABSTRACT: IMRT and helical tomotherapy for head and neck cancer (HNC) treatment are associated with higher doses to certain non-target tissues than traditional static beam techniques. We hypothesized that this may lead to higher acute mucosal and hematologic toxicities. This analysis was limited to 178 patients receiving ≥60 Gy with concurrent weekly cisplatin. Radiation delivery used 3D-CRT in 41 patients (23%), conventional IMRT in 56 patients (31%), and helical tomotherapy in 81 patients (46%). Acute mucositis rates, weekly hematologic parameters, and ability to deliver planned chemotherapy cycles were examined for each patient during their course of chemoradiotherapy. Analysis showed patients were well balanced with regard to sex, age, and stage. Treatment time, as assessed by delivered monitor units, varied significantly between the 3D-CRT (median = 502), IMRT (median = 1087), and tomotherapy (median = 6757) cohorts. Acute mucositis grades did not significantly differ between the three subsets. Through six weeks of chemoradiotherapy, the median decline in hemoglobin was 15.6%, the median decline in platelets was 30.6%, and the median decline in leukocytes was 51.5%, but these drops were not significantly different between treatment cohorts. Chemotherapy was discontinued or held secondary to hematologic toxicity in 12% of 3D-CRT patients, 5% of IMRT patients and 15% of tomotherapy patients (p = 0.14). In conclusion, HNC patients undergoing high dose radiation with concurrent weekly cisplatin chemotherapy, the longer beam-on times and larger volumes of low-to-moderate radiation doses to non-target tissues associated with modern IMRT delivery techniques do not appear to result in increased acute hematologic or mucosal toxicities.
  Technology in cancer research & treatment 03/2013;
• Article: Tomotherapy Radiosurgery for Arteriovenous Malformations - Current Possibilities and Future Options with Helical Tomotherapy Dynamic Jaws?

  S Krause, S Beck, O Schramm, K Schubert, H Hauswald, A Zabel-du Bois, K Herfarth, J Debus, F Sterzing
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  ABSTRACT: This planning study was performed to compare stereotactic linac based radiosurgery of Arteriovenous Malformations (AVM) with current Helical Tomotherapy (HT) and future HT techniques. For 10 patients with AVM, dose distributions and treatment times of "regular" HT delivery (Reg 2.5/1/0.6 cm field width), Running-Start-Stop Treatment (RSS 5/2.5 cm), Axial Mode (Axial 5 cm) and Dynamic Jaw/Dynamic Couch delivery with a maximum field width of 5 cm (DJDC 5) were analysed and compared to linac-based stereotactic radiosurgery. Axial produced the fastest treatment (Axial 4:47 min vs. Linac 32:42 min) at the cost of large brain exposure (V10% 289 ml). Except for Reg 0.6, all other HT techniques achieved significantly shorter treatment times than linac-based treatment (e.g. Reg 1, 19:42 min, DJDC 6:30 min). However, high-dose brain exposure (V60%) was higher in all HT plans (e.g. Reg 0.6, 10 ml, Linac 9 ml), and only Reg 0.6 showed better low-dose exposure (V10% of 167 ml vs. 199 ml, not significant). Neither current nor future HT modes in their current version outperformed linac-based stereotactic radiosurgery. However, AVM with special geometry might still benefit from HT.
  Technology in cancer research & treatment 03/2013;
• Article: Collagen-hydroxyapatite/Cisplatin Drug Delivery Systems for Locoregional Treatment of Bone Cancer.

  E Andronescu, A Ficai, M G Albu, V Mitran, M Sonmez, D Ficai, R Ion, A Cimpean
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  ABSTRACT: In this paper, the synthesis and characterization of novel cisplatin-loaded collagen (COLL)/hydroxyapatite (HA) composite materials are presented. The composite materials were designed to obtain a COLL: HA weight ratio close to the bone composition. The content of embedded cisplatin was chosen to assure a concentration of cisplatin of 6 and 10 μM, respectively, into the culture media used in cell culture experiments. These cisplatin delivery systems were characterized by determining the physico-chemical properties of the composite material, the drug release process as well as their biological activity. Based on the in vitro data that showed the cytotoxic, anti-proliferative and anti-invasive activities of these multifunctional systems on G292 osteosarcoma cells in dependence on the cisplatin concentration released in culture medium, we conclude that the newly developed COLL/HA-cisplatin drug delivery system could be a feasible approach for locoregional chemotherapy of bone cancer.
  Technology in cancer research & treatment 03/2013;
• Article: Recent Advances and Prospects in the Isolation by Size of Epithelial Tumor Cells (ISET) Methodology.

  Y-C Ma, L Wang, F-L Yu
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  ABSTRACT: Current technologies to identify and characterize circulating tumor cells (CTCs) and _ circulating tumor microemboli (CTMs) among hundreds of millions of leukocytes in the bloodstream can be classified into tumor-marker-dependent and -independent technology. Isolation by size of epithelial tumor cells (ISET) is a tumor-marker-independent technology, in which CTCs are isolated by filtration without use of tumor-associated markers, as a result of their large size relative to circulating blood leukocytes. ISET allows cytomorphological, immunocytological, and genetic characterization of CTCs and CTMs. It offers a number of advantages, including retention of cell morphology; non-antigen dependence; amenability of cells to further interrogation by immunolabeling, fluorescence in situ hybridization, and RNA/DNA analysis; ability to isolate CTMs; reliability. Therefore, morphological-analysis-based and antigen-independent ISET methodology can yield more accurate and objective characterization of epithelial-mesenchymal transition. We can evaluate efficacy of _chemotherapy and radiotherapy and other cancer-targeting therapies by using xenografts that are suitable models for mechanistic studies of ISET-isolated CTC/CTM biology. In addition, a new _ISET-based device could be designed to increase sensitivity to CTCs/CTMs greatly and reduce the number of CTCs/CTMs directly during the blood flow, thus decreasing the _possibility of tumor recurrence and metastasis while retaining normal blood cells. This article reviews recent advances and prospects in ISET methodology and provides new insights into ISET methodology, with important implications for the clinical management of cancer patients.
  Technology in cancer research & treatment 02/2013;
• Article: Stereotactic Body Radiotherapy with Helical Tomotherapy for Pain Palliation in Spine Metastasis.

  M S Kim, K C Keum, J H Cha, J H Kim, J S Seong, C G Lee, K C Nam, W S Koom
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  ABSTRACT: To evaluate the pain response, local tumor control and toxicity of stereotactic body radiotherapy (SBRT) with helical tomotherapy (HT) in the patients with spine metastasis. From May 2009 to June 2010, 22 patients with 31 lesions were treated by SBRT. Dose scheme were 24 Gy in 3 fractions (87.1%), 30 Gy in 5 fractions (9.7%), and 16 Gy in a single fraction (3.2%). Pain was assessed using a numerical rating scale. Analgesic consumption was recalculated into the daily oral morphine-equivalent dose (OMED). The response criteria of International Bone Metastases Consensus Group (IBMCG) was used. The median follow-up duration was 10 months (range 3-23 months). After SBRT the mean pain score decreased significantly (4.32 before SBRT, 0.71 at 3 months). However, median OMED didn't decrease until 3 months after SBRT (Median OMED; 34.5 mg before SBRT, 45 mg at 3 months). Pain response rate and pain progression-free survival rate at 3 month was 96.8 and 93.5%, respectively. Local progression-free survival rate at 3 month was 93.5%. There was no severe acute toxicity. SBRT with HT is a safe and effective treatment modality for local tumor control and pain palliation associated with spine metastasis.
  Technology in cancer research & treatment 02/2013;
• Article: Resonance Raman and Raman Spectroscopy for Breast Cancer Detection.

  C-H Liu, Y Zhou, Y Sun, J Y Li, L X Zhou, S Boydston-White, V Masilamani, K Zhu, Y Pu, R R Alfano
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  ABSTRACT: Raman spectroscopy is a sensitive method to detect early changes of molecular _composition and structure that occur in lesions during carcinogenesis. The Raman spectra of normal, benign and cancerous breast tissues were investigated in vitro using a near-infrared (NIR) Raman system of 785 nm excitation and confocal micro resonance Raman system of 532 nm excitation. A total number of 491 Raman spectra were acquired from normal, benign and cancerous breast tissues taken from 15 patients. When the 785 nm excitation was used, the dominant peaks in the spectra were characteristic of the vibrations of proteins and lipids. The differences between the normal and cancerous breast tissues were observed in both the peak positions and the intensity ratios of the characteristic Raman peaks in the spectral region of 700-1800 cm21. With 532 nm excitation, the resonance Raman (RR) spectra exhibited a robust pattern of peaks within the region of 500-4000 cm21. The intensities of four distinct peaks at 1156, 1521, 2854 and 3013 cm21 detected in the spectra collected from normal breast tissue were found to be stronger in comparison with those collected from cancerous breast tissue. The twelve dramatically enhanced characteristic peaks, including the enhanced amide II peak at 1548 cm21 in the spectra collected from cancerous breast tissue, distinguished the cancerous tissue from the normal tissue. Principal component analysis (PCA) combined with support vector machine (SVM) analysis of the Raman and RR spectral data yielded a high performance in the classification of cancerous and benign lesions from normal breast tissue.
  Technology in cancer research & treatment 02/2013;
• Article: The Role of Regularization in Deformable Image Registration for Head and Neck Adaptive Radiotherapy.

  D Ciardo, M Peroni, M Riboldi, D Alterio, G Baroni, R Orecchia
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  ABSTRACT: Deformable image registration provides a robust mathematical framework to quantify morphological changes that occur along the course of external beam radiotherapy treatments. As clinical reliability of deformable image registration is not always guaranteed, algorithm regularization is commonly introduced to prevent sharp discontinuities in the quantified deformation and achieve anatomically consistent results. In this work we analyzed the influence of regularization on two different registration methods, i.e. B-Splines and Log Domain Diffeomorphic Demons, implemented in an open-source platform. We retrospectively analyzed the simulation computed tomography (CTsim) and the corresponding re-planning computed tomography (CTrepl) scans in 30 head and neck cancer patients. First, we investigated the influence of regularization levels on hounsfield units (HU) information in 10 test patients for each considered method. Then, we compared the registration results of the open-source implementation at selected best performing regularization levels with a clinical commercial software on the remaining 20 patients in terms of mean volume overlap, surface and center of mass distances between manual outlines and propagated structures. The regularized B-Splines method was not statistically different from the commercial software. The tuning of the regularization parameters allowed open-source algorithms to achieve better results in deformable image registration for head and neck patients, with the additional benefit of a framework where regularization can be tuned on a patient specific basis.
  Technology in cancer research & treatment 02/2013;
• Article: Isolation and Identification of Renal Cell Carcinoma-derived Peptides Associated with GP96.

  H-Z Li, C-W Li, C-Y Li, B-F Zhang, L-T Li, J-M Li, J-N Zheng, J-W Chang
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  ABSTRACT: We determined the possible associated determinants and analyzed whether gp96-_associated antigenic peptides can be found in renal cell carcinoma (RCC). The gp96-peptide complexes were chromatographically purified from resected tumor tissue of RCC patients. SDS-PAGE and Western blot analysis confirmed gp96 using the gp96 monoclonal antibody, and its concentration was measured using BCA. Approximately 20 to 50 μg gp96-peptide complexes was obtained from 1 g RCC tissue. The mass spectrometry (MS) analysis of the eluted peptides included the initial profiling using matrix-assisted laser desorption/ionization time-of-flight MS. Quadrupole time-of-flight MS combined with the Mascot search engine was used to identify the peptides and find proteins from primary sequence databases. MS analysis results demonstrated that the mass range of peptide associated with gp96 was from 1046.48 to 3501.56 Da. Further research confirmed the sequences of two gp96-associated peptides, namely, LVPLEGWGGNVM and PPVYYVPYVVL. However, the original protein of the two peptides could not be found. The results demonstrated that the gp96-associated peptides are small molecular peptides, and the two peptides are deduced to be RCC-associated peptides. The identified peptides were confirmed to be associated with gp96 using the protocols described above. However, the specificity and relevance of the association to the immunogenicity of gp96 remains to be examined. Further analysis must be accomplished before the findings can be applied in peptide vaccine.
  Technology in cancer research & treatment 02/2013;
• Article: Improving the Therapeutic Ratio in Stereotactic Radiosurgery: Optimizing Treatment Protocols Based on Kinetics of Repair of Sublethal Radiation Damage.

  B Andisheh, D Belkic, P Mavroidis, M Alahverdi, B K Lind
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  ABSTRACT: Sublethal damage after radiation exposure may become lethal or be repaired according to repair kinetics. This is a well-established concept in conventional radiotherapy. It also plays an important role in single-dose stereotactic radiotherapy treatments, often called stereotactic radiosurgery, when duration of treatment is extended due to source decay or treatment planning protocol. The purpose of this study is to look into the radiobiological characteristics of normal brain tissue and treatment protocols and find a way to optimize the time course of these protocols. The general problem is nonlinear and can be solved numerically. For numerical optimization of the time course of radiation protocol, a biexponential repair model with slow and fast components was considered. With the clinically imposed constraints of a fixed total dose and total treatment time, three parameters for each fraction (dose-rate, fraction duration, time of each fraction) were simultaneously optimized. A biological optimization can be performed by maximizing the therapeutic difference between tumor control probability and normal tissue complication probability. Specifically, for gamma knife radiosurgery, this approach can be implemented for normal brain tissue or tumor voxels separately in a treatment plan. Differences in repair kinetics of normal tissue and tumors can be used to find clinically optimized protocols. Thus, in addition to considering the physical dose in tumor and normal tissue, we also account for repair of sublethal damage in both these tissues.
  Technology in cancer research & treatment 02/2013;