Contrast-enhanced dynamic MR imaging of parasellar tumor using fast spin-echo sequence

International Nuclear Information System (INIS)

Kusunoki, Katsusuke; Ohue, Shiro; Ichikawa, Haruhisa; Saito, Masahiro; Sadamoto, Kazuhiko; Sakaki, Saburo; Miki, Hitoshi.

1995-01-01

We have applied a new dynamic MRI technique that uses a fast spin-echo sequence to parasellar tumors. This sequence has less susceptible effect and better spatial resolution than a gradient echo sequence, providing faster images than a short spin-echo sequence does. Image was obtained in the coronal or sagittal plane using a 1.5T clinical MRI system, and then, dynamic MR images were acquired every 10 to 20 sec after administration of Gd-DTPA (0.1 mmol/kg). The subjects were 12 patients (5 microadenomas, 5 macroadenomas and 2 Rathke's cleft cysts) and 5 normal volunteers. As for volunteers, the cavernous sinus, pituitary stalk and posterior pituitary gland were contrasted on the first image, followed by visualization of the proximal portion adjacent to the junction of the infundibulum and the anterior pituitary gland, and finally by contrasting the distal portion of the anterior pituitary gland. There was a difference with respect to tumor contrast between microadenomas and macroadenomas. In the case of the macroadenomas, the tumor was contrasted at the same time as, or faster than the anterior pituitary gland, while with the microadenomas the tumor was enhanced later than the anterior pituitary gland. No enhancement with contrast medium was seen in Rathke's cleft cysts. In addition, it was possible to differentiate a recurrent tumor from a piece of muscle placed at surgery since the images obtained by the fast spin-echo sequence were clearer than those obtained by gradient echo sequence. (author)

Gd-DTPA MR imaging enhancement of spinal cord tumors

International Nuclear Information System (INIS)

Dillon, W.P.; Bolla, K.; Mark, A.S.; Tsudura, J.S.; Norman, D.; Newton, T.H.

1987-01-01

Nineteen patients with suspected spinal cord tumors were imaged with T1- and T2-weighted sequences before and after the administration of Gd-DTPA (0.1 mmol/kg). Eleven of the 19 patients had spinal cord tumors (three unproven). Eight of 11 patients had intramedullary tumors (four astrocytomas, two ependymomas) and two had extra-medullary tumors (one meningioma, one metastatic melanoma). Other lesions studied include idiopathic syringomyelia (two), spinal arteriovenous malformation (AVM) (one), posttraumatic arachnoiditis (one), and cord infarct (one). All of the tumors enhanced after the administration of Gd-DTPA. Spinal cord enhancement was also noted in association with a spinal cord AVM, a suspected cord infarct, and in the patient with severe arachnoiditis. No enhancement was present in patients with idiopathic or posttraumatic syringomyelia or in the three normal patients. In six of the patients, enhancement was critical in confirming disease that was questionable on the precontrast MR images. Gadolinium enhancement allowed differentiation of tumor from postoperative changes in two patients with spinal cord tumors. Enhanced images localized the lesion more accurately than precontrast MR images in eight patients. In four patients a lesion could only be detected after the administration of contrast. The postcontrast images better defined the margin of tumor from surrounding edema, operative scarring, and cord cavitation. The AVM case had enhancement of slowly flowing veins with Gd-DTPA posterior to an ischemic cord segment. Gd-DTPA enhancement is extremely useful in the detection and therapeutic assessment of spinal cord tumors; however, enhancement is not specific for tumors and should be interpreted in light of the clinical setting

Enhanced inflammation and attenuated tumor suppressor pathways are associated with oncogene-induced lung tumors in aged mice

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Aging is often accompanied by a dramatic increase in cancer susceptibility. To gain insights into how aging affects tumor susceptibility, we generated a conditional mouse model in which oncogenic KrasG12D was activated specifically in lungs of young (3-5 months) and old (19-24 months) mice. Activati...

Contrast-enhanced CISS imaging of cerebellopontine angle tumors

Energy Technology Data Exchange (ETDEWEB)

Tozaki, Mitsuhiro; Toyoda, Keiko; Hata, Yuichi; Fukuda, Yasushi; Fukuda, Kunihiko [Jikei Univ., Tokyo (Japan). School of Medicine; Katano, Shuichi

1999-10-01

Our purpose of this study was to evaluate the clinical usefulness of contrast-enhanced CISS-3DFT MR imaging for the diagnosis of CP angle tumors. CISS-3DFT MR imaging is expected for screening procedure of acoustic schwannoma because of excellent spatial resolution. Recently, we discovered contrast enhancement effect on CISS sequence in spite of heavily T{sub 2}-weighted images. Fourteen patients with CP angle tumors were performed on a 1.0 T MR unit. Transaxial CISS-3DFT MRI was obtained both before and after intravenous injections of Gd-DTPA. Multiplanar reconstructions (MPRs) were performed in all cases. Contrast enhancement effect of CP angle tumors, and the relationship between tumors and the adjacent cranial nerves were evaluated. Contrast enhancement effect of the tumors was present in all cases in spite of heavily T{sub 2}-weighted images of CISS sequences. In the internal auditory canal, relationship between the tumors and the cranial nerves was demonstrated in 6 cases (6/9). In the cerebellopontine cistern, all cases were demonstrated (11/11). Contrast-enhanced CISS-3DFT MR imaging with a good contrast resolution and an excellent spatial resolution is useful for the diagnosis of CP angle tumors. (author)

Common genetic variations in cell cycle and DNA repair pathways associated with pediatric brain tumor susceptibility

DEFF Research Database (Denmark)

Fahmideh, Maral Adel; Lavebratt, Catharina; Schüz, Joachim

2016-01-01

Knowledge on the role of genetic polymorphisms in the etiology of pediatric brain tumors (PBTs) is limited. Therefore, we investigated the association between single nucleotide polymorphisms (SNPs), identified by candidate gene-association studies on adult brain tumors, and PBT risk. The study is...... cycle and DNA repair pathways variations associated with susceptibility to adult brain tumors also seem to be associated with PBT risk, suggesting pediatric and adult brain tumors might share similar etiological pathways....

MR imaging of gestational trophoblastic tumor: role of gadolinium enhancement

International Nuclear Information System (INIS)

Choi, Si Young; Byun, Jae Young; Kim, Bum Su; Yun, Young Hyun; Mun, Kyung Mi; Park, Kyung Sin; Kim, Byung Kee; Bae, Seog Nyeon; Shinn, Kyung Sub.

1997-01-01

The purpose of this study is to investigate the role of gadolinium enhanced MR imaging in the evaluation of gestational trophoblastic tumors (invasive mole and choriocarcinoma). Pre-enhanced T1-and T2-weighted images and gadolinium enhanced T1-weighted images of 34 gestational trophoblastic tumors (15 choriocarcinomas, 19 invasive moles) were retrospectively evaluated and enhancement patterns were analyzed. Morphologica differences and structural characteristics were analyzed by the evaluation of tumor margin, patterns of hemorrhagic necroses, the development of intratumoral vascularity, and molar villi. Graded scores of MR findings between pre- and gadolinium enhanced images were based on the following criteria : 1) visualization of tumor margin 2) distinction between tumor necrosis and zone of trophoblastic proliferation ; and 3) molar villi. Statistical differences between graded scores of pre- and post-enhanced images were analyzed. Gadolinium enhanced MR imaging was helpful for the visualization of tumor characteristics in gestational trophoblastic tumors and in differential diagnosis between invasive mole and choriocarcinoma. (author). 16 refs., 4 tabs., 4 figs

Combined value of susceptibility weighted imaging and dynamic susceptibility-weighted contrast-enhanced MR perfusion-weighted imaging in brain astrocytoma grading

International Nuclear Information System (INIS)

Wang Xiaochun; Zhang Hui; Qin Jiangbo; Wang Le; Wu Xiaofeng

2012-01-01

Objective: To assess the value of combination of susceptibility weighted imaging (SWI) and dynamic susceptibility-weighted contrast-enhanced (DSC) perfusion-weighted magnetic resonance imaging in astrocytoma grading. Methods: SWI and DSC scans were performed in 82 patients with pathologically confirmed astrocytoma. The patient group consisted of grade Ⅱ (15), grade Ⅲ (10), and grade Ⅳ (57). The intratumoral susceptibility signal intensity (ITSS) and relative cerebral blood volume (rCBV) max were used to determine the grade of astrocytomas by Kruskal Wallis test, Welch test, Spearman correlation coefficients, Pearson correlation coefficients, and receiver operating characteristic curve (ROC)statistic methods. Results: There were no ITSS in 14 cases of low-grade astrocytomas, the degree of ITSS were grade 1 to 3 in anaplastic astrocytomas, the degree of ITSS were grade 3 in all of the glioblastomas, the degree of ITSS were significant difference in all grades (H=71.96, P<0.01). rCBV max in grade Ⅱ, grade Ⅲ and grade Ⅳ astrocytomas were 1.26 ± 0.42, 3.59 ± 2.09 and 8.34 ± 1.16 respectively, rCBV max were significant difference in all grades (F'=681.72, P<0.01). ITSS showed significant correlation with rCBV max (r=0.72, P<0.01) and tumor grades (r=0.89, P<0.01), and rCBV and tumor grades showed significant correlation (r=0.78, P<0.01). Area under the ROC curve application SWI, DSC, SWI and DSC in differentiation of the grade Ⅱ and grade Ⅲ astrocytomas were 0.99, 0.93, 1.00, differentiate grade Ⅲ from grade Ⅳ were 0.70, 0.94, 0.94, and differentiate high-grade from low-grade astrocytomas were 1.00, 0.99, 1.00. Conclusions: ITSS is helpful to determine the grade of astrocytomas. The use of SWI in combination with DSC may improve the diagnostic accuracy of astrocytoma grading. (authors)

Biochemical evidence for deficient DNA repair leading to enhanced G2 chromatid radiosensitivity and susceptibility to cancer

International Nuclear Information System (INIS)

Gantt, R.; Parshad, R.; Price, F.M.; Sanford, K.K.

1986-01-01

Human tumor cells and cells from cancer-prone individuals, compared with those from normal individuals, show a significantly higher incidence of chromatid breaks and gaps seen in metaphase cells immediately after G2 X irradiation. Previous studies with DNA repair-deficient mutants and DNA repair inhibitors strongly indicate that the enhancement results from a G2 deficiency(ies) in DNA repair. We report here biochemical evidence for a DNA repair deficiency that correlates with the cytogenetic studies. In the alkaline elution technique, after a pulse label with radioactive thymidine in the presence of 3-acetylaminobenzamide (a G2-phase blocker) and X irradiation, DNA from tumor or cancer-prone cells elutes more rapidly during the postirradiation period than that from normal cells. These results indicate that the DNA of tumor and cancer-prone cells either repairs more slowly or acquires more breaks than that of normal cells; breaks can accumulate during incomplete or deficient repair processes. The kinetic difference between normal and tumor or cancer-prone cells in DNA strand-break repair reaches a maximum within 2 h, and this maximum corresponds to the kinetic difference in chromatid aberration incidence following X irradiation reported previously. These findings support the concept that cells showing enhanced G2 chromatid radiosensitivity are deficient in DNA repair. The findings could also lead to a biochemical assay for cancer susceptibility

Enhanced experimental tumor metastasis with age in senescence-accelerated mouse

International Nuclear Information System (INIS)

Shimizu, Kosuke; Kinouchi Shimizu, Naomi; Asai, Tomohiro; Oku, Naoto; Tsukada, Hideo

2008-01-01

Tumor metastasis is affected by the host immune surveillance system. Since aging may attenuate the host immune potential, the experimental tumor metastasis may be enhanced with age. In the present study, we investigated this alteration of experimental tumor metastasis with age. We used senescence-accelerated mice prone 10 (SAMP10) as a model of aged animals. Natural killer cell (NK) activity, as an indicator of immune surveillance potential, in 8-month-old (aged) SAMP10 mice was observed to be much lower than that in 2-month-old (young) mice. When we examined the in vivo trafficking of lung-metastatic K1735M2 melanoma cells in SAMP10 with positron emission tomography (PET), K1735M2 cells labeled with [2- 18 F]2-deoxy-2-fluoro-D-glucose ([ 18 F]FDG) were observed in both young and aged SAMP10 just after injection of the cells, whereas the clearance of 18 F from the lungs was retarded in aged animals. The accumulation of 5-[ 125 I]iodo-2'-deoxyuridine ([ 125 I]IUdR)-labeled K1735M2 cells in the lungs of SAMP10 at 24 h after injection was significantly higher in aged mice. Corresponding to these results, the number of metastatic colonies in the lung was larger in the aged SAMP10 of the experimental tumor metastasis model. The present study demonstrated that the aging process produced a susceptible environment allowing the tumor cells to metastasize due to decrease in the host immune surveillance potential with age. (author)

Neural - levelset shape detection segmentation of brain tumors in dynamic susceptibility contrast enhanced and diffusion weighted magnetic resonance images

International Nuclear Information System (INIS)

Vijayakumar, C.; Bhargava, Sunil; Gharpure, Damayanti Chandrashekhar

2008-01-01

A novel Neuro - level set shape detection algorithm is proposed and evaluated for segmentation and grading of brain tumours. The algorithm evaluates vascular and cellular information provided by dynamic contrast susceptibility magnetic resonance images and apparent diffusion coefficient maps. The proposed neural shape detection algorithm is based on the levels at algorithm (shape detection algorithm) and utilizes a neural block to provide the speed image for the level set methods. In this study, two different architectures of level set method have been implemented and their results are compared. The results show that the proposed Neuro-shape detection performs better in differentiating the tumor, edema, necrosis in reconstructed images of perfusion and diffusion weighted magnetic resonance images. (author)

Recurrent medulloblastoma: Frequency of tumor enhancement on Gd-DTPA MR imaging

International Nuclear Information System (INIS)

Rollins, N.; Mendelsohn, D.; Mulne, A.; Barton, R.; Diehl, J.; Reyes, N.; Sklar, F.

1990-01-01

Thirty-two children with medulloblastoma were evaluated postoperatively with conventional and gadolinium-enhanced MR imaging. Eleven patients had abnormal cranial MR studies; nine of these had recurrent tumor. In six patients recurrent tumor enhanced with Gd, while in the other three patients recurrent tumor did not enhance. The remaining two patients had areas of abnormal Gd enhancement that were caused by radiation-induced breakdown of the blood-brain barrier rather than by recurrent tumor. This study shows that not all recurrent medulloblastoma enhances and that the absence of Gd enhancement does not necessarily indicate the absence of recurrent tumor

Enhanced pairing susceptibility in a photodoped two-orbital Hubbard model

Science.gov (United States)

Werner, Philipp; Strand, Hugo U. R.; Hoshino, Shintaro; Murakami, Yuta; Eckstein, Martin

2018-04-01

Local spin fluctuations provide the glue for orbital-singlet spin-triplet pairing in the doped Mott insulating regime of multiorbital Hubbard models. At large Hubbard repulsion U , the pairing susceptibility is nevertheless tiny because the pairing interaction cannot overcome the suppression of charge fluctuations. Using nonequilibrium dynamical mean field simulations of the two-orbital Hubbard model, we show that out of equilibrium the pairing susceptibility in this large-U regime can be strongly enhanced by creating a photoinduced population of the relevant charge states. This enhancement is supported by the long lifetime of photodoped charge carriers and a built-in cooling mechanism in multiorbital Hubbard systems.

Low-dose radiation enhances therapeutic HPV DNA vaccination in tumor-bearing hosts.

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Tseng, Chih-Wen; Trimble, Cornelia; Zeng, Qi; Monie, Archana; Alvarez, Ronald D; Huh, Warner K; Hoory, Talia; Wang, Mei-Cheng; Hung, Chien-Fu; Wu, T-C

2009-05-01

Current therapeutic approaches to treatment of patients with bulky cervical cancer are based on conventional in situ ablative modalities including cisplatin-based chemotherapy and radiation therapy. The 5-year survival of patients with nonresectable disease is dismal. Because over 99% of squamous cervical cancer is caused by persistent infection with an oncogenic strain of human papillomavirus (HPV), particularly type 16 and viral oncoproteins E6 and E7 are functionally required for disease initiation and persistence, HPV-targeted immune strategies present a compelling opportunity in which to demonstrate proof of principle. Sublethal doses of radiation and chemotherapeutic agents have been shown to have synergistic effect in combination with either vaccination against cancer-specific antigens, or with passive transfer of tumor-specific cytotoxic T lymphocytes (CTLs). Here, we explored the combination of low-dose radiation therapy with DNA vaccination with calreticulin (CRT) linked to the mutated form of HPV-16 E7 antigen (E7(detox)), CRT/E7(detox) in the treatment of E7-expressing TC-1 tumors. We observed that TC-1 tumor-bearing mice treated with radiotherapy combined with CRT/E7(detox) DNA vaccination generated significant therapeutic antitumor effects and the highest frequency of E7-specific CD8(+) T cells in the tumors and spleens of treated mice. Furthermore, treatment with radiotherapy was shown to render the TC-1 tumor cells more susceptible to lysis by E7-specific CTLs. In addition, we observed that treatment with radiotherapy during the second DNA vaccination generated the highest frequency of E7-specific CD8(+) T cells in the tumors and spleens of TC-1 tumor-bearing mice. Finally, TC-1 tumor-bearing mice treated with the chemotherapy in combination with radiation and CRT/E7(detox) DNA vaccination generate significantly enhanced therapeutic antitumor effects. The clinical implications of the study are discussed.

Contrast-enhanced MR imaging monitoring of acute tumor response to chemotherapy

International Nuclear Information System (INIS)

Ranney, D.F.; Cohen, J.M.; Antich, P.P.; Endman, W.A.; Kulkarni, P.; Weinreb, J.C.; Giovanella, B.

1987-01-01

Treatment responses of human malignant melanomas were monitored at millimeter resolution in athymic mice by injecting a new polymeric contrast agent, Gd-DTPA-dextran (0.1 mmol Gd/kg, intravenously). Proton MR imaging (0.35 T, spin-echo, repetition time = 0.5 second, echo time = 50 msec) was performed 30 hours after administering diphtheria toxin. Pre-contrast medium images revealed only homogeneous intermediate-intensity tumor masses. Post-contrast medium images of untreated (viable) tumors demonstrated 32% enhancement throughout the entire mass. Post-contrast medium images of toxin-treated tumors revealed marked enhancement (65%) of the histologically viable outer rims, lesser enhancement (38%) of heavily damaged subregions, and no enhancement of dead tumor. These acute, contrast medium-enhanced MR images accurately identified tumor subregions that survived for longer than one week

Benign and malignant hepatocellular tumors: evaluation of tumoral enhancement after mangafodipir trisodium injection on MR imaging

International Nuclear Information System (INIS)

Coffin, C.M.; Diche, T.; Mahfouz, A.E.; Alexandre, M.; Caseiro-Alves, F.; Rahmouni, A.; Vasile, N.; Mathieu, D.

1999-01-01

The aim of this work was to study the ability of mangafodipir trisodium (Mn-DPDP)-enhanced MR imaging in differentiating malignant from benign hepatocellular tumors. Eleven patients with pathologically proved hepatocellular carcinomas, six with focal nodular hyperplasias, and one with a single hepatocellular adenoma were examined by spin-echo and gradient-echo T1-weighted sequences before, 1 h after, and 24 h after intravenous injection of Mn-DPDP (5 μmol/kg). Quantitative analysis including enhancement and lesion-to-liver contrast-to-noise ratio, and qualitative analysis including the presence of a central area and a capsule were done on pre- and post-Mn-DPDP-enhanced images. Enhancement was observed in all the tumors with significant improvement (p < 0.05) in contrast-to-noise ratio 1 h after, and 24 h after intravenous injection of Mn-DPDP. There were no significant differences in the mean enhancement and the mean contrast-to-noise ratio (CNR) between benign and malignant tumors. No enhancement was seen within internal areas observed in 7 hepatocellular carcinomas, and in 5 focal nodular hyperplasias, and within capsules which were observed in 9 hepatocellular carcinomas. In our study, Mn-DPDP increased CNR of both benign and malignant tumors but did not enable differentiation between benign and malignant tumors of hepatocellular nature. (orig.)

Tumor suppressors: enhancers or suppressors of regeneration?

Science.gov (United States)

Pomerantz, Jason H.; Blau, Helen M.

2013-01-01

Tumor suppressors are so named because cancers occur in their absence, but these genes also have important functions in development, metabolism and tissue homeostasis. Here, we discuss known and potential functions of tumor suppressor genes during tissue regeneration, focusing on the evolutionarily conserved tumor suppressors pRb1, p53, Pten and Hippo. We propose that their activity is essential for tissue regeneration. This is in contrast to suggestions that tumor suppression is a trade-off for regenerative capacity. We also hypothesize that certain aspects of tumor suppressor pathways inhibit regenerative processes in mammals, and that transient targeted modification of these pathways could be fruitfully exploited to enhance processes that are important to regenerative medicine. PMID:23715544

Identification of activated enhancers and linked transcription factors in breast, prostate, and kidney tumors by tracing enhancer networks using epigenetic traits.

Science.gov (United States)

Rhie, Suhn Kyong; Guo, Yu; Tak, Yu Gyoung; Yao, Lijing; Shen, Hui; Coetzee, Gerhard A; Laird, Peter W; Farnham, Peggy J

2016-01-01

Although technological advances now allow increased tumor profiling, a detailed understanding of the mechanisms leading to the development of different cancers remains elusive. Our approach toward understanding the molecular events that lead to cancer is to characterize changes in transcriptional regulatory networks between normal and tumor tissue. Because enhancer activity is thought to be critical in regulating cell fate decisions, we have focused our studies on distal regulatory elements and transcription factors that bind to these elements. Using DNA methylation data, we identified more than 25,000 enhancers that are differentially activated in breast, prostate, and kidney tumor tissues, as compared to normal tissues. We then developed an analytical approach called Tracing Enhancer Networks using Epigenetic Traits that correlates DNA methylation levels at enhancers with gene expression to identify more than 800,000 genome-wide links from enhancers to genes and from genes to enhancers. We found more than 1200 transcription factors to be involved in these tumor-specific enhancer networks. We further characterized several transcription factors linked to a large number of enhancers in each tumor type, including GATA3 in non-basal breast tumors, HOXC6 and DLX1 in prostate tumors, and ZNF395 in kidney tumors. We showed that HOXC6 and DLX1 are associated with different clusters of prostate tumor-specific enhancers and confer distinct transcriptomic changes upon knockdown in C42B prostate cancer cells. We also discovered de novo motifs enriched in enhancers linked to ZNF395 in kidney tumors. Our studies characterized tumor-specific enhancers and revealed key transcription factors involved in enhancer networks for specific tumor types and subgroups. Our findings, which include a large set of identified enhancers and transcription factors linked to those enhancers in breast, prostate, and kidney cancers, will facilitate understanding of enhancer networks and mechanisms

Loci controlling lymphocyte production of interferon gamma after alloantigen stimulation in vitro and their co-localization with genes controlling lymphocyte infiltration of tumors and tumor susceptibility

Czech Academy of Sciences Publication Activity Database

Lipoldová, Marie; Havelková, Helena; Badalová, Jana; Vojtíšková, Jarmila; Quan, L.; Krulová, Magdalena; Sohrabi, Yahya; Stassen, A. P. M.; Demant, P.

2010-01-01

Roč. 59, č. 2 (2010), s. 203-213 ISSN 0340-7004 R&D Projects: GA MŠk(CZ) LC06009; GA AV ČR IAA500520606; GA ČR GD310/08/H077 Institutional research plan: CEZ:AV0Z50520514 Keywords : Tumor susceptibility * Genetic control of interferon gamma production * Lymphocyte infiltration of tumors Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.293, year: 2010

MDM2 SNP309, gene-gene interaction, and tumor susceptibility: an updated meta-analysis

Directory of Open Access Journals (Sweden)

Wu Wei

2011-05-01

Full Text Available Abstract Background The tumor suppressor gene p53 is involved in multiple cellular pathways including apoptosis, transcriptional control, and cell cycle regulation. In the last decade it has been demonstrated that the single nucleotide polymorphism (SNP at codon 72 of the p53 gene is associated with the risk for development of various neoplasms. MDM2 SNP309 is a single nucleotide T to G polymorphism located in the MDM2 gene promoter. From the time that this well-characterized functional polymorphism was identified, a variety of case-control studies have been published that investigate the possible association between MDM2 SNP309 and cancer risk. However, the results of the published studies, as well as the subsequent meta-analyses, remain contradictory. Methods To investigate whether currently published epidemiological studies can clarify the potential interaction between MDM2 SNP309 and the functional genetic variant in p53 codon72 (Arg72Pro and p53 mutation status, we performed a meta-analysis of the risk estimate on 27,813 cases with various tumor types and 30,295 controls. Results The data we reviewed indicated that variant homozygote 309GG and heterozygote 309TG were associated with a significant increased risk of all tumor types (homozygote comparison: odds ratio (OR = 1.25, 95% confidence interval (CI = 1.13-1.37; heterozygote comparison: OR = 1.10, 95% CI = 1.03-1.17. We also found that the combination of GG and Pro/Pro, TG and Pro/Pro, GG and Arg/Arg significantly increased the risk of cancer (OR = 3.38, 95% CI = 1.77-6.47; OR = 1.88, 95% CI = 1.26-2.81; OR = 1.96, 95% CI = 1.01-3.78, respectively. In a stratified analysis by tumor location, we also found a significant increased risk in brain, liver, stomach and uterus cancer (OR = 1.47, 95% CI = 1.06-2.03; OR = 2.24, 95%CI = 1.57-3.18; OR = 1.54, 95%CI = 1.04-2.29; OR = 1.34, 95%CI = 1.07-1.29, respectively. However, no association was seen between MDM2 SNP309 and tumor susceptibility

Contrast-enhanced fast fluid-attenuated inversion recovery MR imaging in patients with brain tumors

International Nuclear Information System (INIS)

Kim, Chan Kyo; Na, Dong Gyu; Ryoo, Wook Jae; Byun Hong Sik; Yoon, Hye Kyung; Kim, Jong hyun

2000-01-01

To assess the feasibility of contrast-enhanced fast fluid-attenuated inversion recovery (fast FLAIR) MR imaging in patients with brain tumors. This study involved 31 patients with pathologically proven brain tumors and nine with clinically diagnosed metastases. In all patients, T2-weighted, fast FLAIR, images were visual contrast-enhanced T1-weighted MR images were obtained. Contrast-enhanced fast FLAIR images were visually compared with other MR sequences in terms of tumor conspicuity. In order to distinguish tumor and surrounding edema, contrast-enhanced fast FLAIR images were compared with fast FLAIR and T2-weighted images. The tumor-to- white matter contrast-to-noise ratios (CNRs), as demonstrated by T2-weighted, fast FLAIR, contrast-enhanced fast FLAIR and contrast-enhanced T1-weighted imaging, were quantitatively assessed and compared. For the visual assessment of tumor conspicuity, contrast-enhanced fast FLAIR image imaging superior to fast FLAIR in 60% of cases (24/40), and superior to T2-weighted in 70% (28/40). Contrast-enhanced fast FLAIR imaging was inferior to contrast-enhanced T1-weighted in 58% of cases (23/40). For distinguishing between tumor and surrounding edema, contrast-enhanced fast FLAIR imaging was superior to fast FLAIR or T2-weighted in 22 of 27 tumors with peritumoral edema (81%). Quantitatively, CNR was the highest on contrast-enhanced fast FLAIR image and the lowest on fast FLAIR. For the detection of leptomeningeal metastases, contrast-enhanced fast FLAIR was partially superior to contrast-enhanced T1-weighted imaging in two of three high-grade gliomas. Although contrast-enhanced fast FLAIR imaging should not be seen as a replacement for conventional modalities, it provides additional informaton for assessment of the extent of glial cell tumors and leptomeningeal metastases in patients with brain tumors. (author)

Cyclophosphamide Enhances Human Tumor Growth in Nude Rat Xenografted Tumor Models

Directory of Open Access Journals (Sweden)

Yingjen Jeffrey Wu

2009-02-01

Full Text Available The effect of the immunomodulatory chemotherapeutic agent cyclophosphamide (CTX on tumor growth was investigated in primary and metastatic intracerebral and subcutaneous rat xenograft models. Nude rats were treated with CTX (100 mg/kg, intraperitoneally 24 hours before human ovarian carcinoma (SKOV3, small cell lung carcinoma (LX-1 SCLC, and glioma (UW28, U87MG, and U251 tumor cells were inoculated subcutaneously, intraperitoneally, or in the right cerebral hemisphere or were infused into the right internal carotid artery. Tumor development was monitored and recorded. Potential mechanisms were further investigated. Only animals that received both CTX and Matrigel showed consistent growth of subcutaneous tumors. Cyclophosphamide pretreatment increased the percentage (83.3% vs 0% of animals showing intraperitoneal tumors. In intracerebral implantation tumor models, CTX pretreatment increased the tumor volume and the percentage of animals showing tumors. Cyclophosphamide increased lung carcinoma bone and facial metastases after intra-arterial injection, and 20% of animals showed brain metastases. Cyclophosphamide transiently decreased nude rat white blood cell counts and glutathione concentration, whereas serum vascular endothelial growth factor was significantly elevated. Cyclophosphamide also increased CD31 reactivity, a marker of vascular endothelium, and macrophage (CD68-positive infiltration into glioma cell-inoculated rat brains. Cyclophosphamide may enhance primary and metastatic tumor growth through multiple mechanisms, including immune modulation, decreased response to oxidative stress, increased tumor vascularization, and increased macrophage infiltration. These findings may be clinically relevant because chemotherapy may predispose human cancer subjects to tumor growth in the brain or other tissues.

Tumor-Triggered Geometrical Shape Switch of Chimeric Peptide for Enhanced in Vivo Tumor Internalization and Photodynamic Therapy.

Science.gov (United States)

Han, Kai; Zhang, Jin; Zhang, Weiyun; Wang, Shibo; Xu, Luming; Zhang, Chi; Zhang, Xianzheng; Han, Heyou

2017-03-28

Geometrical shape of nanoparticles plays an important role in cellular internalization. However, the applicability in tumor selective therapeutics is still scarcely reported. In this article, we designed a tumor extracellular acidity-responsive chimeric peptide with geometrical shape switch for enhanced tumor internalization and photodynamic therapy. This chimeric peptide could self-assemble into spherical nanoparticles at physiological condition. While at tumor extracellular acidic microenvironment, chimeric peptide underwent detachment of acidity-sensitive 2,3-dimethylmaleic anhydride groups. The subsequent recovery of ionic complementarity between chimeric peptides resulted in formation of rod-like nanoparticles. Both in vitro and in vivo studies demonstrated that this acidity-triggered geometrical shape switch endowed chimeric peptide with accelerated internalization in tumor cells, prolonged accumulation in tumor tissue, enhanced photodynamic therapy, and minimal side effects. Our results suggested that fusing tumor microenvironment with geometrical shape switch should be a promising strategy for targeted drug delivery.

Assessment of brain metastases by means of dynamic susceptibility contrast enhanced MRI

International Nuclear Information System (INIS)

Knopp, M.; Wenz, F.; Debus, J.; Hentrich, H.R.

2002-01-01

Full text: To assess if pre therapeutic measurements of regional cerebral blood flow (rCBF) and volume (rCVB) are able to predict the response of brain metastases to radiation therapy and to assess the influence of radiosurgery on rCBF and rCBV on brain metastases and normal surrounding tissue. We examined 25 patients with brain metastases prior to high dose radiosurgery with conventional T1 and T2 weighted MRI and dynamic susceptibility contrast enhanced MRI (DSC MRI). For DSC MRI 55 T2*w GE images of two sections were acquired after bolus administration of 0.1 mmol/kg gadoteridol (ProHance) for the simultaneous measurement of brain feeding arteries and brain tissue. This allowed an absolute quantification of rCBF and rCBV. Follow-up examinations were performed 6 weeks and 3 months after radiotherapy and the acquired perfusion data were related to a 3 point scale of treatment outcome. Radiosurgery was performed by a linear accelerator with a 80% isodose of 18-20 Gv. For treatment planning the heads of the patients were immobilized by a cask mask to avoid head movement. DSC MRI was able to assess perfusion data in all patients. Higher pre therapeutic rCBV seems to predict a poor treatment outcome. After radiosurgery patients with tumor remission and stable disease presented a decrease of rCBV over time regardless of temporary tumor volume increase. Patients with tumor progression at the 3 month followup presented an increase of rCBV. Effects on normal surrounding tissue could not be observed. DSC MRI using Gadoteridol allows the non-invasive assessment of rCBV and rCBF of brain metastases and its changes due to radiosurgery. The method may also be able to predict treatment outcome. Furthermore radiofrequency effects on surrounding unaffected tissue can be monitored. Copyright (2002) Blackwell Science Pty Ltd

Sonoporation enhances liposome accumulation and penetration in tumors with low EPR.

Science.gov (United States)

Theek, Benjamin; Baues, Maike; Ojha, Tarun; Möckel, Diana; Veettil, Seena Koyadan; Steitz, Julia; van Bloois, Louis; Storm, Gert; Kiessling, Fabian; Lammers, Twan

2016-06-10

The Enhanced Permeability and Retention (EPR) effect is a highly variable phenomenon. To enhance EPR-mediated passive drug targeting to tumors, several different pharmacological and physical strategies have been evaluated over the years, including e.g. TNFα-treatment, vascular normalization, hyperthermia and radiotherapy. Here, we systematically investigated the impact of sonoporation, i.e. the combination of ultrasound (US) and microbubbles (MB), on the tumor accumulation and penetration of liposomes. Two different MB formulations were employed, and their ability to enhance liposome accumulation and penetration was evaluated in two different tumor models, which are both characterized by relatively low levels of EPR (i.e. highly cellular A431 epidermoid xenografts and highly stromal BxPC-3 pancreatic carcinoma xenografts). The liposomes were labeled with two different fluorophores, enabling in vivo computed tomography/fluorescence molecular tomography (CT-FMT) and ex vivo two-photon laser scanning microscopy (TPLSM). In both models, in spite of relatively high inter- and intra-individual variability, a trend towards improved liposome accumulation and penetration was observed. In treated tumors, liposome concentrations were up to twice as high as in untreated tumors, and sonoporation enhanced the ability of liposomes to extravasate out of the blood vessels into the tumor interstitium. These findings indicate that sonoporation may be a useful strategy for improving drug targeting to tumors with low EPR. Copyright © 2016 Elsevier B.V. All rights reserved.

Usefulness of superparamagnetic iron oxide particle (AMI-25) enhanced MR imaging for the diagnosis of liver tumors

International Nuclear Information System (INIS)

Hirohashi, Shinji; Hirohashi, Rina; Uchida, Hideo; Kachi, Kenji; Ohtomo, Kuni; Uchiyama, Gyou; Niitsu, Mamoru; Itai, Yuji.

1994-01-01

The purpose of this study was to clarify the usefulness of SPIO-enhanced MRI in the diagnosis of liver tumors in comparison with contrast enhanced CT. The subjects were forty patients with 154 nodules in the liver. We compared SPIO-enhanced MRI with contrast-enhanced CT in terms of tumor-liver contrast and detectability of liver tumors. In terms of tumor liver contrast, SPIO-enhanced MRI was equal or superior to contrast-enhanced CT in 82% of cases. In the detectability of liver tumor, SPIO-enhanced MRI detected more tumors than contrast-enhanced CT, especially small tumors. Tumors undetected by SPIO-enhanced MRI that were detected by contrast-enhanced CT and/or plain MRI were adenomatous hyperplasia and inflammatory pseudotumor according to fine needle biopsy. There were no severe complications of SPIO-enhanced MRI. In conclusion, SPIO-enhanced MRI will be more useful than contrast-enhanced CT in the diagnosis of liver tumors. SPIO-enhanced MRI may be a promising diagnostic method for the detection of hepatic tumors, especially small ones. (author)

Susceptibility Imaging in Glial Tumor Grading; Using 3 Tesla Magnetic Resonance (MR) System and 32 Channel Head Coil.

Science.gov (United States)

Aydin, Omer; Buyukkaya, Ramazan; Hakyemez, Bahattin

2017-01-01

Susceptibility weighted imaging (SWI) is a velocity compensated, high-resolution three-dimensional (3D) spoiled gradient-echo sequence that uses magnitude and filtered-phase data. SWI seems to be a valuable tool for non-invasive evaluation of central nervous system gliomas. Relative cerebral blood volume (rCBV) ratio is one of the best noninvasive methods for glioma grading. Degree of intratumoral susceptibility signal (ITSS) on SWI correlates with rCBV ratio and histopathological grade. This study investigated the effectiveness of ITSS grading and rCBV ratio in preoperative assessment. Thirty-one patients (17 males and 14 females) with histopathogical diagnosis of glial tumor undergoing routine cranial MRI, SWI, and perfusion MRI examinations between October 2011 and July 2013 were retrospectively enrolled. All examinations were performed using 3T apparatus with 32-channel head coil. We used ITSS number for SWI grading. Correlations between SWI grade, rCBV ratio, and pathological grading were evaluated. ROC analysis was performed to determine the optimal rCBV ratio to distinguish between high-grade and low-grade glial tumors. There was a strong positive correlation between both pathological and SWI grading. We determined the optimal rCBV ratio to discriminate between high-grade and low-grade tumors to be 2.21. In conclusion, perfusion MRI and SWI using 3T MR and 32-channel head coil may provide useful information for preoperative glial tumor grading. SWI can be used as an accessory to perfusion MR technique in preoperative tumor grading.

Tungsten Targets the Tumor Microenvironment to Enhance Breast Cancer Metastasis

Science.gov (United States)

Bolt, Alicia M.; Sabourin, Valérie; Molina, Manuel Flores; Police, Alice M.; Negro Silva, Luis Fernando; Plourde, Dany; Lemaire, Maryse; Ursini-Siegel, Josie; Mann, Koren K.

2015-01-01

The number of individuals exposed to high levels of tungsten is increasing, yet there is limited knowledge of the potential human health risks. Recently, a cohort of breast cancer patients was left with tungsten in their breasts following testing of a tungsten-based shield during intraoperative radiotherapy. While monitoring tungsten levels in the blood and urine of these patients, we utilized the 66Cl4 cell model, in vitro and in mice to study the effects of tungsten exposure on mammary tumor growth and metastasis. We still detect tungsten in the urine of patients’ years after surgery (mean urinary tungsten concentration at least 20 months post-surgery = 1.76 ng/ml), even in those who have opted for mastectomy, indicating that tungsten does not remain in the breast. In addition, standard chelation therapy was ineffective at mobilizing tungsten. In the mouse model, tungsten slightly delayed primary tumor growth, but significantly enhanced lung metastasis. In vitro, tungsten did not enhance 66Cl4 proliferation or invasion, suggesting that tungsten was not directly acting on 66Cl4 primary tumor cells to enhance invasion. In contrast, tungsten changed the tumor microenvironment, enhancing parameters known to be important for cell invasion and metastasis including activated fibroblasts, matrix metalloproteinases, and myeloid-derived suppressor cells. We show, for the first time, that tungsten enhances metastasis in an animal model of breast cancer by targeting the microenvironment. Importantly, all these tumor microenvironmental changes are associated with a poor prognosis in humans. PMID:25324207

Diagnostic value of dynamic contrast-enhanced MRI for submucosal palatal tumors

International Nuclear Information System (INIS)

Matsuzaki, Hidenobu; Yanagi, Yoshinobu; Hara, Marina; Katase, Naoki; Hisatomi, Miki; Unetsubo, Teruhisa; Konouchi, Hironobu; Takenobu, Toshihiko

2012-01-01

Objectives: To evaluate the diagnostic value of dynamic contrast-enhanced MRI (DCE-MRI) for differentiating between benign and malignant tumors in the palate. Materials and methods: 26 patients with submucosal palatal tumors were preoperatively examined using DCE-MRI. Their maximum contrast index (CImax), time of CImax (Tmax), and washout ratios (WR300 and WR600) were determined from contrast index curves. The submucosal palatal tumors were divided into two groups according to their Tmax values: the early enhancement group (Tmax 2 = 0.92, P < 0.001). Conclusions: Tmax is a useful parameter for distinguishing between benign and malignant submucosal palatal tumors.

CpG oligodeoxynucleotides are potent enhancers of radio- and chemoresponses of murine tumors

International Nuclear Information System (INIS)

Mason, Kathryn A.; Neal, Robert; Hunter, Nancy; Ariga, Hisanori; Ang, Kian; Milas, Luka

2006-01-01

Background and purpose: Synthetic oligodeoxynucleotides (ODNs) containing unmethylated cytosine-guanine (CpG) motifs bind to Toll-like receptor 9 (TLR9) and stimulate both innate and adaptive immune reactions and possess anti-tumor activity. We recently reported that CpG ODN 1826 strongly enhances radioresponse of both immunogenic [Milas L, Mason K, Ariga H, et al. CpG oligodeoxynucleotide enhances tumor response to radiation. Cancer Res 2004;64:5074-7] and non-immunogenic [Mason KA, Ariga H, Neal R, et al. Targeting toll-like receptor-9 with CpG oligodeoxynucleotides enhances tumor response to fractionated radiotherapy. Clin Cancer Res 2005;11:361-9] murine tumors. Using two immunogenic murine tumors, a fibrosarcoma (FSa) and a mammary carcinoma (MCa-K), the present study explored whether CpG ODN 1826 also improves the response of murine tumors to the chemotherapeutic agent docetaxel (DOC). Materials and methods: CpG ODN 1826 (100 μg) was given sc three times: when leg tumors were 6 mm, when they grew to 8 mm and again 1 week later. DOC (33 mg/kg iv) and local tumor radiation (10 Gy) were given when tumors were 8 mm. Effects of the treatments were assayed by tumor growth delay, defined as days for tumors to grow from 8 to 12 mm in diameter. Results: Treatment with CpG ODN 1826 resulted in strongly enhanced response of FSa tumors to radiation and MCa-K tumors to the chemotherapeutic agent DOC. Enhancement of tumor treatment response was demonstrated by a strong prolongation in the primary tumor treatment endpoint, tumor growth delay. Coincidentally, this treatment also resulted in a higher rate of tumor cure than that observed after tumor radiotherapy or chemotherapy alone. When all three agents were combined the effect was comparable to that of the combination of CpG ODN 1826 with radiation in the case of FSa or of the combination of CpG ODN 1826 with DOC in the case of MCa-K. Conclusion: Overall results show that CpG ODN 1826 can markedly improve tumor response

Ultrasound-enhanced delivery of doxorubicin/all-trans retinoic acid-loaded nanodiamonds into tumors.

Science.gov (United States)

Li, Huanan; Zeng, Deping; Wang, Zhenyu; Fang, Liaoqiong; Li, Faqi; Wang, Zhibiao

2018-03-14

To build up a combined therapy strategy to address limitations of the enhanced permeability and retention (EPR) effect and improve the efficiency of tumor therapy. A pH-sensitive nanocomplex for co-delivery of doxorubicin (DOX) and all-trans retinoic acid (ATRA) was developed based on nanodiamonds (DOX/ATRA-NDs) to enhance intracellular retention of drugs. Meanwhile, ultrasound was employed to enhance tumor vascular penetration of DOX-ATRA-NDs. The distribution of DOX/ATRA-NDs in the tumor tissues increased threefold when ultrasound was applied at 1 MHz and 0.6 W/cm 2 . Comparing with unmodified chemotherapeutics, the combined therapy induced more tumor cells apoptosis and greater tumor growth inhibition in both liver and breast tumor models. DOX-ATRA-NDs demonstrate great potential in clinical applications.

Automated Processing of Dynamic Contrast-Enhanced MRI: Correlation of Advanced Pharmacokinetic Metrics with Tumor Grade in Pediatric Brain Tumors.

Science.gov (United States)

Vajapeyam, S; Stamoulis, C; Ricci, K; Kieran, M; Poussaint, T Young

2017-01-01

Pharmacokinetic parameters from dynamic contrast-enhanced MR imaging have proved useful for differentiating brain tumor grades in adults. In this study, we retrospectively reviewed dynamic contrast-enhanced perfusion data from children with newly diagnosed brain tumors and analyzed the pharmacokinetic parameters correlating with tumor grade. Dynamic contrast-enhanced MR imaging data from 38 patients were analyzed by using commercially available software. Subjects were categorized into 2 groups based on pathologic analyses consisting of low-grade (World Health Organization I and II) and high-grade (World Health Organization III and IV) tumors. Pharmacokinetic parameters were compared between the 2 groups by using linear regression models. For parameters that were statistically distinct between the 2 groups, sensitivity and specificity were also estimated. Eighteen tumors were classified as low-grade, and 20, as high-grade. Transfer constant from the blood plasma into the extracellular extravascular space (K trans ), rate constant from extracellular extravascular space back into blood plasma (K ep ), and extracellular extravascular volume fraction (V e ) were all significantly correlated with tumor grade; high-grade tumors showed higher K trans , higher K ep , and lower V e . Although all 3 parameters had high specificity (range, 82%-100%), K ep had the highest specificity for both grades. Optimal sensitivity was achieved for V e , with a combined sensitivity of 76% (compared with 71% for K trans and K ep ). Pharmacokinetic parameters derived from dynamic contrast-enhanced MR imaging can effectively discriminate low- and high-grade pediatric brain tumors. © 2017 by American Journal of Neuroradiology.

Hierarchical Targeting Strategy for Enhanced Tumor Tissue Accumulation/Retention and Cellular Internalization.

Science.gov (United States)

Wang, Sheng; Huang, Peng; Chen, Xiaoyuan

2016-09-01

Targeted delivery of therapeutic agents is an important way to improve the therapeutic index and reduce side effects. To design nanoparticles for targeted delivery, both enhanced tumor tissue accumulation/retention and enhanced cellular internalization should be considered simultaneously. So far, there have been very few nanoparticles with immutable structures that can achieve this goal efficiently. Hierarchical targeting, a novel targeting strategy based on stimuli responsiveness, shows good potential to enhance both tumor tissue accumulation/retention and cellular internalization. Here, the recent design and development of hierarchical targeting nanoplatforms, based on changeable particle sizes, switchable surface charges and activatable surface ligands, will be introduced. In general, the targeting moieties in these nanoplatforms are not activated during blood circulation for efficient tumor tissue accumulation, but re-activated by certain internal or external stimuli in the tumor microenvironment for enhanced cellular internalization. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Enhancement of tumor radioresponse by combined chemotherapy in murine hepatocarcinoma

International Nuclear Information System (INIS)

Seong, Jin Sil; Kim, Sung Hee; Suh, Chang Ok

2000-01-01

The purpose of this study was to identify drugs that can enhance radioresponse of murine hepatocarcinoma. C3H/HeJ mice bearing 8 mm tumors of murine hepatocarcinoma, HCa-l, were treated with 25 Gy radiation and one of the following drugs: 5-Fu, 150 mg/kg; adriamycin, 8 mg/kg; cisplatin, 6 mg/kg; paclitaxel, 40 mg/kg; and gemcitabine, 50 mg/kg. Tumor response to the treatment was determined by tumor growth delay assay and by enhancement factor. Apoptotic level was assessed in tissue sections. Expression of regulating molecules was analyzed by western blotting for p53, 8c1-2, Sax, Bel-XL, Bd-XS, and p21 WAF1/CIP1 . Among the drugs tested, only gemcitabine enhanced the antitumor effect of radiation, with enhancement factor of 1.6. Induction of apoptosis by a combination of gerncitabine and radiation was shown as only additive level. In analysis of radiation-induced expression of regulating molecules, the most significant change by combining gemcitabine was activation of p21 WAF1/CIP1 . Gemcitabine is the first drug showing an enhancement of radioresponse in murine hepatocarcinoma, when combined with radiation. The key element of enhancement is thought to be p21 WAF1/CIP1

Enhancement of tumor radioresponse by combined chemotherapy in murine hepatocarcinoma

Energy Technology Data Exchange (ETDEWEB)

Seong, Jin Sil; Kim, Sung Hee; Suh, Chang Ok [College of Medicine, Yonsei Univ., Seoul (Korea, Republic of)

2000-12-01

The purpose of this study was to identify drugs that can enhance radioresponse of murine hepatocarcinoma. C3H/HeJ mice bearing 8 mm tumors of murine hepatocarcinoma, HCa-l, were treated with 25 Gy radiation and one of the following drugs: 5-Fu, 150 mg/kg; adriamycin, 8 mg/kg; cisplatin, 6 mg/kg; paclitaxel, 40 mg/kg; and gemcitabine, 50 mg/kg. Tumor response to the treatment was determined by tumor growth delay assay and by enhancement factor. Apoptotic level was assessed in tissue sections. Expression of regulating molecules was analyzed by western blotting for p53, 8c1-2, Sax, Bel-XL, Bd-XS, and p21{sup WAF1/CIP1}. Among the drugs tested, only gemcitabine enhanced the antitumor effect of radiation, with enhancement factor of 1.6. Induction of apoptosis by a combination of gerncitabine and radiation was shown as only additive level. In analysis of radiation-induced expression of regulating molecules, the most significant change by combining gemcitabine was activation of p21 {sup WAF1/CIP1}. Gemcitabine is the first drug showing an enhancement of radioresponse in murine hepatocarcinoma, when combined with radiation. The key element of enhancement is thought to be p21{sup WAF1/CIP1}.

Chemotherapy-Induced Macrophage Infiltration into Tumors Enhances Nanographene-Based Photodynamic Therapy.

Science.gov (United States)

Zhao, Yang; Zhang, Chenran; Gao, Liquan; Yu, Xinhe; Lai, Jianhao; Lu, Dehua; Bao, Rui; Wang, Yanpu; Jia, Bing; Wang, Fan; Liu, Zhaofei

2017-11-01

Increased recruitment of tumor-associated macrophages (TAM) to tumors following chemotherapy promotes tumor resistance and recurrence and correlates with poor prognosis. TAM depletion suppresses tumor growth, but is not highly effective due to the effects of tumorigenic mediators from other stromal sources. Here, we report that adoptive macrophage transfer led to a dramatically enhanced photodynamic therapy (PDT) effect of 2-(1-hexyloxyethyl)-2-devinyl pyropheophor-bide-alpha (HPPH)-coated polyethylene glycosylated nanographene oxide [GO(HPPH)-PEG] by increasing its tumor accumulation. Moreover, tumor treatment with commonly used chemotherapeutic drugs induced an increase in macrophage infiltration into tumors, which also enhanced tumor uptake and the PDT effects of GO(HPPH)-PEG, resulting in tumor eradication. Macrophage recruitment to tumors after chemotherapy was visualized noninvasively by near-infrared fluorescence and single-photon emission CT imaging using F4/80-specific imaging probes. Our results demonstrate that chemotherapy combined with GO(HPPH)-PEG PDT is a promising strategy for the treatment of tumors, especially those resistant to chemotherapy. Furthermore, TAM-targeted molecular imaging could potentially be used to predict the efficacy of combination therapy and select patients who would most benefit from this treatment approach. Cancer Res; 77(21); 6021-32. ©2017 AACR . ©2017 American Association for Cancer Research.

Measurement of weak electric currents in copper wire phantoms using MRI: influence of susceptibility enhancement.

Science.gov (United States)

Huang, Ruiwang; Posnansky, Oleg; Celik, Abdullah; Oros-Peusquens, Ana-Maria; Ermer, Veronika; Irkens, Marco; Wegener, H-Peter; Shah, N Jon

2006-08-01

The use of magnetic resonance imaging (MRI)-based methods for the direct detection of neuronal currents is a topic of intense investigation. Much experimental work has been carried out with the express aim of establishing detection thresholds and sensitivity to flowing currents. However, in most of these experiments, magnetic susceptibility enhancement was ignored. In this work, we present results that show the influence of a susceptibility artefact on the detection threshold and sensitivity. For this purpose, a novel phantom, consisting of a water-filled cylinder with two wires of different materials connected in series, was constructed. Magnitude MR images were acquired from a single slice using a gradient-echo echo planar imaging (EPI) sequence. The data show that the time course of the detected MR signal magnitude correlates very well with the waveform of the input current. The effect of the susceptibility artefacts arising from the two different wires was examined by comparing the magnitudes of the MR signals at different voxel locations. Our results indicate the following: (1) MR signal enhancement arising from the magnetic susceptibility effect influences the detection sensitivity of weak current; (2) the detection threshold and sensitivity are phantom-wire dependent; (3) sub-mu A electric current detection in a phantom is possible on a 1.5-T MR scanner in the presence of susceptibility enhancement.

[Circadian rhythm in susceptibility of mice to the anti-tumor drug carboplatin].

Science.gov (United States)

Lu, X H; Yin, L J

1994-12-01

The platinum-containing compounds has become a major chemical agent in the treatment of cancer. A circadian rhythm in the susceptibility of rodents and human being to cisplatin has been demonstrated, the maximal tolerance being found in the animal's active phase. Carboplatin is a second generation analog. Two studies were performed on mice with carboplatin under 12:12 light dark cycle to study its chronotoxicity and chronoeffectiveness. In study I, single intraperitoneal injection of 192mg/kg (LD50) carboplatin was given to four groups of mice at four different circadian stage. It was found that at 50% the overall mortality of mice, there was a mortality difference of 28% for mice receiving the drug at 9 a.m. to 71% for mice receiving drug at 9 p.m. It demonstrated that carboplatin was better tolerated in the animal's early sleep phase. In study II, S180 tumor-bearing mice were treated with 50mg/kg of carboplatin. The longest mean survival time and the lowest marrow toxicity occurred in the group which received the drug at the beginning of the sleep phase. It showed that the susceptibility of mice to carboplatin is circadian stage dependent. These data clearly demonstrate that, by timing the administration of drugs according to body rhythms, such as the host susceptibility-resistance rhythm to a drug, one can gain a therapeutic advantage over an approach which ignores such rhythms.

Multi-Parametric MRI and Texture Analysis to Visualize Spatial Histologic Heterogeneity and Tumor Extent in Glioblastoma.

Science.gov (United States)

Hu, Leland S; Ning, Shuluo; Eschbacher, Jennifer M; Gaw, Nathan; Dueck, Amylou C; Smith, Kris A; Nakaji, Peter; Plasencia, Jonathan; Ranjbar, Sara; Price, Stephen J; Tran, Nhan; Loftus, Joseph; Jenkins, Robert; O'Neill, Brian P; Elmquist, William; Baxter, Leslie C; Gao, Fei; Frakes, David; Karis, John P; Zwart, Christine; Swanson, Kristin R; Sarkaria, Jann; Wu, Teresa; Mitchell, J Ross; Li, Jing

2015-01-01

Genetic profiling represents the future of neuro-oncology but suffers from inadequate biopsies in heterogeneous tumors like Glioblastoma (GBM). Contrast-enhanced MRI (CE-MRI) targets enhancing core (ENH) but yields adequate tumor in only ~60% of cases. Further, CE-MRI poorly localizes infiltrative tumor within surrounding non-enhancing parenchyma, or brain-around-tumor (BAT), despite the importance of characterizing this tumor segment, which universally recurs. In this study, we use multiple texture analysis and machine learning (ML) algorithms to analyze multi-parametric MRI, and produce new images indicating tumor-rich targets in GBM. We recruited primary GBM patients undergoing image-guided biopsies and acquired pre-operative MRI: CE-MRI, Dynamic-Susceptibility-weighted-Contrast-enhanced-MRI, and Diffusion Tensor Imaging. Following image coregistration and region of interest placement at biopsy locations, we compared MRI metrics and regional texture with histologic diagnoses of high- vs low-tumor content (≥80% vs heterogeneity to identify regional tumor-rich biopsy targets.

T cells enhance gold nanoparticle delivery to tumors in vivo

Science.gov (United States)

Kennedy, Laura C.; Bear, Adham S.; Young, Joseph K.; Lewinski, Nastassja A.; Kim, Jean; Foster, Aaron E.; Drezek, Rebekah A.

2011-12-01

Gold nanoparticle-mediated photothermal therapy (PTT) has shown great potential for the treatment of cancer in mouse studies and is now being evaluated in clinical trials. For this therapy, gold nanoparticles (AuNPs) are injected intravenously and are allowed to accumulate within the tumor via the enhanced permeability and retention (EPR) effect. The tumor is then irradiated with a near infrared laser, whose energy is absorbed by the AuNPs and translated into heat. While reliance on the EPR effect for tumor targeting has proven adequate for vascularized tumors in small animal models, the efficiency and specificity of tumor delivery in vivo, particularly in tumors with poor blood supply, has proven challenging. In this study, we examine whether human T cells can be used as cellular delivery vehicles for AuNP transport into tumors. We first demonstrate that T cells can be efficiently loaded with 45 nm gold colloid nanoparticles without affecting viability or function (e.g. migration and cytokine production). Using a human tumor xenograft mouse model, we next demonstrate that AuNP-loaded T cells retain their capacity to migrate to tumor sites in vivo. In addition, the efficiency of AuNP delivery to tumors in vivo is increased by more than four-fold compared to injection of free PEGylated AuNPs and the use of the T cell delivery system also dramatically alters the overall nanoparticle biodistribution. Thus, the use of T cell chaperones for AuNP delivery could enhance the efficacy of nanoparticle-based therapies and imaging applications by increasing AuNP tumor accumulation.

An in-depth characterization of the major psoriasis susceptibility locus identifies candidate susceptibility alleles within an HLA-C enhancer element.

Directory of Open Access Journals (Sweden)

Alex Clop

Full Text Available Psoriasis is an immune-mediated skin disorder that is inherited as a complex genetic trait. Although genome-wide association scans (GWAS have identified 36 disease susceptibility regions, more than 50% of the genetic variance can be attributed to a single Major Histocompatibility Complex (MHC locus, known as PSORS1. Genetic studies indicate that HLA-C is the strongest PSORS1 candidate gene, since markers tagging HLA-Cw*0602 consistently generate the most significant association signals in GWAS. However, it is unclear whether HLA-Cw*0602 is itself the causal PSORS1 allele, especially as the role of SNPs that may affect its expression has not been investigated. Here, we have undertaken an in-depth molecular characterization of the PSORS1 interval, with a view to identifying regulatory variants that may contribute to disease susceptibility. By analysing high-density SNP data, we refined PSORS1 to a 179 kb region encompassing HLA-C and the neighbouring HCG27 pseudogene. We compared multiple MHC sequences spanning this refined locus and identified 144 candidate susceptibility variants, which are unique to chromosomes bearing HLA-Cw*0602. In parallel, we investigated the epigenetic profile of the critical PSORS1 interval and uncovered three enhancer elements likely to be active in T lymphocytes. Finally we showed that nine candidate susceptibility SNPs map within a HLA-C enhancer and that three of these variants co-localise with binding sites for immune-related transcription factors. These data indicate that SNPs affecting HLA-Cw*0602 expression are likely to contribute to psoriasis susceptibility and highlight the importance of integrating multiple experimental approaches in the investigation of complex genomic regions such as the MHC.

AC susceptibility enhancement studies in magnetic systems

International Nuclear Information System (INIS)

Mukherjee, S.; Ranganathan, R.; Chakravarti, A.; Sil, S.

2001-01-01

Enhancement of AC susceptibility has been observed for typical ferromagnets (Gd), reentrant spin glasses like (Fe 1.5 Mn 1.5 Si) and canted spin systems (Ce(Fe 0.96 Al 0.04 ) 2 ). The data have been interpreted with the help of a simulation model based on dry friction-like pinning of domain walls for systems having ferromagnetic domain structures. A strong pinning mechanism appears in the reentrant spin glass like and canted spin systems at low temperatures in addition to the intrinsic one in the ferromagnetic phase. The temperature variation of the pinning potential has been given qualitatively for the reentrant spin glass like systems

Contrast-enhanced color Doppler US in breast cancer: Tumoral vascularity correlated with angiogenesis

Energy Technology Data Exchange (ETDEWEB)

Kim, Eun A; Yoon, Kwon Ha; Yun, Ki Jung; Lee, Kwang Man; Park, Ki Han; Juhng, Seon Kwan; Won, Jong Jin [Wonkwang University School of Medicine, Seoul (Korea, Republic of)

2000-12-15

To evaluate the effects of contrast-enhanced color Doppler ultrasonography (CDUS) on the depiction of vascularity and flow pattern in breast cancer and to determine the relationship between tumoral vascularity and angiogenesis. Twenty-one patients with breast cancer were prospectively evaluated with CDUS before and after injection of the contrast agent (SH U 508A, 2.5g, 300 mg/ml ). The tumoral vascularity was expressed as percentage of color Doppler area, which was measured quantitatively by a computerized program (Ultrasonic Imaging Tool; Soongsil University, Seoul, Korea). The flow pattern (four-patterns; spotty, linear, branching, marginal) of the vascularity was analyzed. After surgery, tumor angiogenesis was assessed by microvessel density. The relationship between the vascularity on CDUS and microvessel density was statistically analyzed. At unenhanced CDUS, tumoral flow signals were detected in 12 lesions (48%); at contrast-enhanced CDUS, 18 lesions (86%). All These 18 lesions showed increased signals, compared with those at unenhanced CDUS. The percentage color Doppler area was 1.86 {+-} 0.48% at unenhanced CDUS and 5.23 {+-} 1.18% at contrast-enhanced CDUS. The flow patterns before contrast injection were spotty pattern in 11 tumors and linear pattern in one; after contrast injection, spotty in 8, linear in 4, branching in 5, and marginal in one. The tumoral vascularity at contrast-enhanced CDUS showed no significant correlation with microvessel density. Contrast-enhanced CDUS seems to be a valuable tool in the depiction of vascularity and characterization of flow pattern in breast cancer. However, tumoral vascularity on CDUS may not reflect tumoral angiogenesis.

Characterization of Metabolic, Diffusion, and Perfusion Properties in GBM: Contrast-Enhancing versus Non-Enhancing Tumor

Directory of Open Access Journals (Sweden)

Adam Autry

2017-12-01

Full Text Available BACKGROUND: Although the contrast-enhancing (CE lesion on T1-weighted MR images is widely used as a surrogate for glioblastoma (GBM, there are also non-enhancing regions of infiltrative tumor within the T2-weighted lesion, which elude radiologic detection. Because non-enhancing GBM (Enh− challenges clinical patient management as latent disease, this study sought to characterize ex vivo metabolic profiles from Enh− and CE GBM (Enh+ samples, alongside histological and in vivo MR parameters, to assist in defining criteria for estimating total tumor burden. Methods: Fifty-six patients with newly diagnosed GBM received a multi-parametric pre-surgical MR examination. Targets for obtaining image-guided tissue samples were defined based on in vivo parameters that were suspicious for tumor. The actual location from where tissue samples were obtained was recorded, and half of each sample was analyzed for histopathology while the other half was scanned using HR-MAS spectroscopy. Results: The Enh+ and Enh− tumor samples demonstrated comparable mitotic activity, but also significant heterogeneity in microvascular morphology. Ex vivo spectroscopic parameters indicated similar levels of total choline and N-acetylaspartate between these contrast-based radiographic subtypes of GBM, and characteristic differences in the levels of myo-inositol, creatine/phosphocreatine, and phosphoethanolamine. Analysis of in vivo parameters at the sample locations were consistent with histological and ex vivo metabolic data. CONCLUSIONS: The similarity between ex vivo levels of choline and NAA, and between in vivo levels of choline, NAA and nADC in Enh+ and Enh− tumor, indicate that these parameters can be used in defining non-invasive metrics of total tumor burden for patients with GBM.

Characterization of Metabolic, Diffusion, and Perfusion Properties in GBM: Contrast-Enhancing versus Non-Enhancing Tumor.

Science.gov (United States)

Autry, Adam; Phillips, Joanna J; Maleschlijski, Stojan; Roy, Ritu; Molinaro, Annette M; Chang, Susan M; Cha, Soonmee; Lupo, Janine M; Nelson, Sarah J

2017-12-01

Although the contrast-enhancing (CE) lesion on T 1 -weighted MR images is widely used as a surrogate for glioblastoma (GBM), there are also non-enhancing regions of infiltrative tumor within the T 2 -weighted lesion, which elude radiologic detection. Because non-enhancing GBM (Enh-) challenges clinical patient management as latent disease, this study sought to characterize ex vivo metabolic profiles from Enh- and CE GBM (Enh+) samples, alongside histological and in vivo MR parameters, to assist in defining criteria for estimating total tumor burden. Fifty-six patients with newly diagnosed GBM received a multi-parametric pre-surgical MR examination. Targets for obtaining image-guided tissue samples were defined based on in vivo parameters that were suspicious for tumor. The actual location from where tissue samples were obtained was recorded, and half of each sample was analyzed for histopathology while the other half was scanned using HR-MAS spectroscopy. The Enh+ and Enh- tumor samples demonstrated comparable mitotic activity, but also significant heterogeneity in microvascular morphology. Ex vivo spectroscopic parameters indicated similar levels of total choline and N-acetylaspartate between these contrast-based radiographic subtypes of GBM, and characteristic differences in the levels of myo-inositol, creatine/phosphocreatine, and phosphoethanolamine. Analysis of in vivo parameters at the sample locations were consistent with histological and ex vivo metabolic data. The similarity between ex vivo levels of choline and NAA, and between in vivo levels of choline, NAA and nADC in Enh+ and Enh- tumor, indicate that these parameters can be used in defining non-invasive metrics of total tumor burden for patients with GBM. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

BRE enhances in vivo growth of tumor cells

International Nuclear Information System (INIS)

Chan, Ben Chung-Lap; Li Qing; Chow, Stephanie Ka-Yee; Ching, Arthur Kar-Keung; Liew, Choong Tsek; Lim, Pak-Leong; Lee, Kenneth Ka-Ho; Chan, John Yeuk-Hon; Chui, Y.-L.

2005-01-01

Human BRE, a death receptor-associating intracellular protein, attenuates apoptotic response of human and mouse tumor cell lines to death receptor stimuli in vitro. In this report, we addressed whether the in vitro antiapoptotic effect of BRE could impact on tumor growth in vivo. We have shown that the mouse Lewis lung carcinoma D122 stable transfectants of human BRE expression vector developed into local tumor significantly faster than the stable transfectants of empty vector and parental D122, in both the syngeneic C57BL/6 host and nude mice. In vitro growth of the BRE stable transfectants was, however, not accelerated. No significant difference in metastasis between the transfectants and the parental D122 was detected. Thus, overexpression of BRE promotes local tumor growth but not metastasis. We conclude that the enhanced tumor growth is more likely due to the antiapoptotic activity of BRE than any direct effect of the protein on cell proliferation

IDH mutant and 1p/19q co-deleted oligodendrogliomas: tumor grade stratification using diffusion-, susceptibility-, and perfusion-weighted MRI

Energy Technology Data Exchange (ETDEWEB)

Lin, Yu; Xing, Zhen; She, Dejun; Yang, Xiefeng; Zheng, Yingyan; Xiao, Zebin; Cao, Dairong [First Affiliated Hospital of Fujian Medical University, Department of Radiology, Fuzhou, Fujian (China); Wang, Xingfu [First Affiliated Hospital of Fujian Medical University, Department of Pathology, Fuzhou (China)

2017-06-15

Currently, isocitrate dehydrogenase (IDH) mutation and 1p/19q co-deletion are proven diagnostic biomarkers for both grade II and III oligodendrogliomas (ODs). Non-invasive diffusion-weighted imaging (DWI), susceptibility-weighted imaging (SWI), and dynamic susceptibility contrast perfusion-weighted imaging (DSC-PWI) are widely used to provide physiological information (cellularity, hemorrhage, calcifications, and angiogenesis) of neoplastic histology and tumor grade. However, it is unclear whether DWI, SWI, and DSC-PWI are able to stratify grades of IDH-mutant and 1p/19q co-deleted ODs. We retrospectively reviewed the conventional MRI (cMRI), DWI, SWI, and DSC-PWI obtained on 33 patients with IDH-mutated and 1p/19q co-deleted ODs. Features of cMRI, normalized ADC (nADC), intratumoral susceptibility signals (ITSSs), normalized maxim CBV (nCBV), and normalized maximum CBF (nCBF) were compared between low-grade ODs (LGOs) and high-grade ODs (HGOs). Receiver operating characteristic curve and logistic regression were applied to determine diagnostic performances. HGOs tended to present with prominent edema and enhancement. nADC, ITSSs, nCBV, and nCBF were significantly different between groups (all P < 0.05). The combination of SWI and DSC-PWI for grading resulted in sensitivity and specificity of 100.00 and 93.33%, respectively. IDH-mutant and 1p/19q co-deleted ODs can be stratified by grades using cMRI and advanced magnetic resonance imaging techniques including DWI, SWI, and DSC-PWI. Combined ITSSs with nCBV appear to be a promising option for grading molecularly defined ODs in clinical practice. (orig.)

Antiangiogenic Effects of Noscapine Enhance Radioresponse for GL261 Tumors

International Nuclear Information System (INIS)

Newcomb, Elizabeth W.; Lukyanov, Yevgeniy; Alonso-Basanta, Michelle; Esencay, Min; Smirnova, Iva; Schnee, Tona; Shao Yongzhao; Devitt, Mary Louise; Zagzag, David; McBride, William; Formenti, Silvia C.

2008-01-01

Purpose: To assess the effects of noscapine, a tubulin-binding drug, in combination with radiation in a murine glioma model. Methods and Materials: The human T98G and murine GL261 glioma cell lines treated with noscapine, radiation, or both were assayed for clonogenic survival. Mice with established GL261 hind limb tumors were treated with noscapine, radiation, or both to evaluate the effect of noscapine on radioresponse. In a separate experiment with the same treatment groups, 7 days after radiation, tumors were resected and immunostained to measure proliferation rate, apoptosis, and angiogenic activity. Results: Noscapine reduced clonogenic survival without enhancement of radiosensitivity in vitro. Noscapine combined with radiation significantly increased tumor growth delay: 5, 8, 13, and 18 days for control, noscapine alone, radiation alone, and the combination treatment, respectively (p < 0.001). To assess the effect of the combination of noscapine plus radiation on the tumor vasculature, tubule formation by the murine endothelial 2H11 cells was tested. Noscapine with radiation significantly inhibited tubule formation compared with radiation alone. By immunohistochemistry, tumors treated with the combination of noscapine plus radiation showed a decrease in BrdU incorporation, an increase in apoptosis by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling, and a decrease in tumor vessel density compared with tumors treated with radiation alone. Conclusion: Noscapine enhanced the sensitivity of GL261 glioma tumors to radiation, resulting in a significant tumor growth delay. An antiangiogenic mechanism contributed to the effect. These findings are clinically relevant, particularly in view of the mild toxicity profile of this drug

Hepatocellular carcinoma: IVIM diffusion quantification for prediction of tumor necrosis compared to enhancement ratios

International Nuclear Information System (INIS)

Kakite, Suguru; Dyvorne, Hadrien A.; Lee, Karen M.; Jajamovich, Guido H.; Knight-Greenfield, Ashley; Taouli, Bachir

2015-01-01

To correlate intra voxel incoherent motion (IVIM) diffusion parameters of liver parenchyma and hepatocellular carcinoma (HCC) with degree of liver/tumor enhancement and necrosis; and to assess the diagnostic performance of diffusion parameters vs. enhancement ratios (ER) for prediction of complete tumor necrosis. In this IRB approved HIPAA compliant study, we included 46 patients with HCC who underwent IVIM diffusion-weighted (DW) MRI in addition to routine sequences at 3.0 T. True diffusion coefficient (D), pseudo-diffusion coefficient (D*), perfusion fraction (PF) and apparent diffusion coefficient (ADC) were quantified in tumors and liver parenchyma. Tumor ER were calculated using contrast-enhanced imaging, and degree of tumor necrosis was assessed using post-contrast image subtraction. IVIM parameters and ER were compared between HCC and background liver and between necrotic and viable tumor components. ROC analysis for prediction of complete tumor necrosis was performed. 79 HCCs were assessed (mean size 2.5 cm). D, PF and ADC were significantly higher in HCC vs. liver (p < 0.0001). There were weak significant negative/positive correlations between D/PF and ER, and significant correlations between D/PF/ADC and tumor necrosis (for D, r 0.452, p < 0.001). Among diffusion parameters, D had the highest area under the curve (AUC 0.811) for predicting complete tumor necrosis. ER outperformed diffusion parameters for prediction of complete tumor necrosis (AUC > 0.95, p < 0.002). D has a reasonable diagnostic performance for predicting complete tumor necrosis, however lower than that of contrast-enhanced imaging

Contrast-Enhanced Endoscopic Ultrasonography for Pancreatic Tumors

Directory of Open Access Journals (Sweden)

Yasunobu Yamashita

2015-01-01

Full Text Available Objectives. To investigate the usefulness of contrast-enhanced endoscopic ultrasonography (CE-EUS for histological differentiation of pancreatic tumors. Methods. CE-EUS was performed for consecutive patients having a pancreatic solid lesion, and tumors were classified into three vascular patterns (hypervascular, isovascular, and hypovascular at two time phases (early-phase and late-phase. Correlation between vascular patterns and histopathology of resected pancreatic cancer (PC tissues was ascertained. Results. The final diagnoses of 147 examined tumors were PC (n=109, inflammatory mass (n=11, autoimmune pancreatitis (n=9, neuroendocrine tumor (n=8, and others (n=10. In late-phase images, 104 of 109 PCs had the hypovascular pattern, for a diagnostic sensitivity and specificity of 94% and 71%, respectively. Of 28 resected PCs, 10 had isovascular, and 18 hypovascular, patterns on the early-phase image. Early-phase isovascular PCs were more likely to be differentiated than were early-phase hypovascular PCs (6 well and 4 moderately differentiated versus 3 well, 14 moderately, and 1 poorly differentiated, P=0.028. Immunostaining revealed that hypovascular areas of early-phase images reflected heterogeneous tumor cells with fibrous tissue, necrosis, and few vessels. Conclusion. CE-EUS could be useful for distinguishing PC from other solid pancreatic lesions and for histological differentiation of PCs.

High-resolution blood-pool-contrast-enhanced MR angiography in glioblastoma: tumor-associated neovascularization as a biomarker for patient survival. A preliminary study

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Puig, Josep; Blasco, Gerard; Remollo, Sebastian; Hernandez, David; Pedraza, Salvador [Hospital Universitari Dr Josep Trueta, Research Unit of Diagnostic Imaging Institute (IDI), Department of Radiology [Girona Biomedical Research Institute] IDIBGI, Girona (Spain); Daunis-i-Estadella, Josep; Mateu, Gloria [University of Girona, Department of Computer Science, Applied Mathematics and Statistics, Girona (Spain); Alberich-Bayarri, Angel [La Fe Polytechnics and University Hospital, Biomedical Imaging Research Group (GIBI230), La Fe Health Research Institute, Valencia (Spain); Essig, Marco [University of Manitoba, Department of Radiology, Winnipeg (Canada); Jain, Rajan [NYU School of Medicine, Division of Neuroradiology, Department of Radiology, New York, NY (United States); Puigdemont, Montserrat [Hospital Universitari Dr Josep Trueta, Catalan Institute of Oncology (ICO), Hospital Cancer Registry, Girona (Spain); Sanchez-Gonzalez, Javier [Philips Healthcare Iberica, Madrid (Spain); Wintermark, Max [Stanford University, Department of Radiology, Neuroradiology Division, Palo Alto, CA (United States)

2016-01-15

The objective of the study was to determine whether tumor-associated neovascularization on high-resolution gadofosveset-enhanced magnetic resonance angiography (MRA) is a useful biomarker for predicting survival in patients with newly diagnosed glioblastomas. Before treatment, 35 patients (25 men; mean age, 64 ± 14 years) with glioblastoma underwent MRI including first-pass dynamic susceptibility contrast (DSC) perfusion and post-contrast T1WI sequences with gadobutrol (0.1 mmol/kg) and, 48 h later, high-resolution MRA with gadofosveset (0.03 mmol/kg). Volumes of interest for contrast-enhancing lesion (CEL), non-CEL, and contralateral normal-appearing white matter were obtained, and DSC perfusion and DWI parameters were evaluated. Prognostic factors were assessed by Kaplan-Meier survival and Cox proportional hazards model. Eighteen (51.42 %) glioblastomas were hypervascular on high-resolution MRA. Hypervascular glioblastomas were associated with higher CEL volume and lower Karnofsky score. Median survival rates for patients with hypovascular and hypervascular glioblastomas treated with surgery, radiotherapy, and chemotherapy were 15 and 9.75 months, respectively (P < 0.001). Tumor-associated neovascularization was the best predictor of survival at 5.25 months (AUC = 0.794, 81.2 % sensitivity, 77.8 % specificity, 76.5 % positive predictive value, 82.4 % negative predictive value) and yielded the highest hazard ratio (P < 0.001). Tumor-associated neovascularization detected on high-resolution blood-pool-contrast-enhanced MRA of newly diagnosed glioblastoma seems to be a useful biomarker that correlates with worse survival. (orig.)

Brain tumors and syndromes in children

NARCIS (Netherlands)

Bleeker, Fonnet E.; Hopman, Saskia M. J.; Merks, Johannes H. M.; Aalfs, Cora M.; Hennekam, Raoul C. M.

2014-01-01

(Brain) tumors are usually a disorder of aged individuals. If a brain tumor occurs in a child, there is a possible genetic susceptibility for this. Such genetic susceptibilities often show other signs and symptoms. Therefore, every child with a brain tumor should be carefully evaluated for the

Background parenchymal enhancement in breast MRIs of breast cancer patients: Impact on tumor size estimation

International Nuclear Information System (INIS)

Baek, Ji Eun; Kim, Sung Hun; Lee, Ah Won

2014-01-01

Objective: To evaluate whether the degree of background parenchymal enhancement affects the accuracy of tumor size estimation based on breast MRI. Methods: Three hundred and twenty-two patients who had known breast cancer and underwent breast MRIs were recruited in our study. The total number of breast cancer cases was 339. All images were assessed retrospectively for the level of background parenchymal enhancement based on the BI-RADS criteria. Maximal lesion diameters were measured on the MRIs, and tumor types (mass vs. non-mass) were assessed. Tumor size differences between the MRI-based estimates and estimates based on pathological examinations were analyzed. The relationship between accuracy and tumor types and clinicopathologic features were also evaluated. Results: The cases included minimal (47.5%), mild (28.9%), moderate (12.4%) and marked background parenchymal enhancement (11.2%). The tumors of patients with minimal or mild background parenchymal enhancement were more accurately estimated than those of patients with moderate or marked enhancement (72.1% vs. 56.8%; p = 0.003). The tumors of women with mass type lesions were significantly more accurately estimated than those of the women with non-mass type lesions (81.6% vs. 28.6%; p < 0.001). The tumor of women negative for HER2 was more accurately estimated than those of women positive for HER2 (72.2% vs. 51.6%; p = 0.047). Conclusion: Moderate and marked background parenchymal enhancement is related to the inaccurate estimation of tumor size based on MRI. Non-mass type breast cancer and HER2-positive breast cancer are other factors that may cause inaccurate assessment of tumor size

Enhanced Tumor Retention Effect by Click Chemistry for Improved Cancer Immunochemotherapy.

Science.gov (United States)

Mei, Ling; Liu, Yayuan; Rao, Jingdong; Tang, Xian; Li, Man; Zhang, Zhirong; He, Qin

2018-05-30

Because of the limited drug concentration in tumor tissues and inappropriate treatment strategies, tumor recurrence and metastasis are critical challenges for effectively treating malignancies. A key challenge for effective delivery of nanoparticles is to reduce uptake by reticuloendothelial system and to enhance the permeability and retention effect. Herein, we demonstrated Cu(I)-catalyzed click chemistry triggered the aggregation of azide/alkyne-modified micelles, enhancing micelles accumulation in tumor tissues. In addition, combined doxorubicin with the adjuvant monophosphoryl lipid A, an agonist of toll-like receptor4, generated immunogenic cell death, which further promoted maturity of dendritic cells, antigen presentation and induced strong effector T cells in vivo. Following combined with anti-PD-L1 therapy, substantial antitumor and metastasis inhibitory effects were achieved because of the reduced PD-L1 expression and regulatory T cells. In addition, effective long-term immunity from memory T cell responses protected mice from tumor recurrence.

Enhancement of 67Ga tumor-to-blood ratios by chelating agent

International Nuclear Information System (INIS)

Saji, Hideo; Yokoyama, Akira; Hata, Naotaka; Misaki, Atsushi; Tanaka, Hisashi.

1980-01-01

Chelating agent, such as, CaEDTA, CaDTPA, D-penicillamine, DMSA, desferoxamine, NTA, cysteine ethyl ester, BAL, α-MPG, phthalein complexone, were tested as a possible contrast enhancing agent for tumor imaging with 67 Ga-citrate. The intravenous administration of a chelating agent to Ehrlich's tumor bearing mice, one hour after the injection of 67 Ga-citrate, accelerated the blood clearance with only a very slight change of activity in the target, increasing the tumor-to-blood ratio, and consequently achieving a better visualization. Among the tested chelating agents, D-penicillamine showed the highest target-to-nontarget ratio at a shorter time: a good tumor-to-blood ratio, performed after 24 hr with non-treated animals, was achieved in only 1-3 hr with post-treated animals. Thus, D-penicillamine hold a considerable promise as a contrast enhancing agent for future clinical use. (author)

MR imaging of renal cell carcinoma. Associations among signal intensity, tumor enhancement, and pathologic findings

Energy Technology Data Exchange (ETDEWEB)

Yabuki, Takayuki; Togami, Izumi; Kitagawa, Takahiro; Sasai, Nobuya; Tsushima, Tomoyasu; Shirasaki, Yoshinori; Hiraki, Yoshio [Okayama Univ. (Japan). Graduate School of Medicine and Dentistry

2003-08-01

The purpose of this study was to compare the MR characteristics of renal cell carcinomas against histologic findings and to assess the correlations among signal intensity, tumor enhancement, and pathologic findings. Fifty-four patients (56 lesions) were examined by MR imaging and then underwent partial or radical nephrectomy. The pathologic diagnosis of all lesions was renal cell carcinoma. All MR examinations were performed as dynamic studies using the same 1.5-T scanner. MR characteristics were compared against pathologic findings after resection, and the correlations among signal intensity, tumor enhancement, and pathologic findings were then assessed. A significant correlation was observed between tumor grade and tumor enhancement, with G3 lesions tending to show little enhancement. Regardless of the histologic classification, G3 tumors were found to contain highly heterotypic cancer cells and very few vessels by histopathologic examination. No significant correlations were noted between the other MR characteristics and pathologic findings. Renal cell carcinomas showing little enhancement tend to be highly malignant lesions based on the pathologic findings. Special consideration is required for these tumors with regard to the selection of surgical intervention and follow-up observation. (author)

MR imaging of renal cell carcinoma. Associations among signal intensity, tumor enhancement, and pathologic findings

International Nuclear Information System (INIS)

Yabuki, Takayuki; Togami, Izumi; Kitagawa, Takahiro; Sasai, Nobuya; Tsushima, Tomoyasu; Shirasaki, Yoshinori; Hiraki, Yoshio

2003-01-01

The purpose of this study was to compare the MR characteristics of renal cell carcinomas against histologic findings and to assess the correlations among signal intensity, tumor enhancement, and pathologic findings. Fifty-four patients (56 lesions) were examined by MR imaging and then underwent partial or radical nephrectomy. The pathologic diagnosis of all lesions was renal cell carcinoma. All MR examinations were performed as dynamic studies using the same 1.5-T scanner. MR characteristics were compared against pathologic findings after resection, and the correlations among signal intensity, tumor enhancement, and pathologic findings were then assessed. A significant correlation was observed between tumor grade and tumor enhancement, with G3 lesions tending to show little enhancement. Regardless of the histologic classification, G3 tumors were found to contain highly heterotypic cancer cells and very few vessels by histopathologic examination. No significant correlations were noted between the other MR characteristics and pathologic findings. Renal cell carcinomas showing little enhancement tend to be highly malignant lesions based on the pathologic findings. Special consideration is required for these tumors with regard to the selection of surgical intervention and follow-up observation. (author)

Systemic perfusion: a method of enhancing relative tumor uptake of radiolabeled monoclonal antibodies

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Wahl, R.L.; Piko, C.R.; Beers, B.A.; Geatti, O.; Johnson, J.; Sherman, P. (Michigan Univ., Ann Arbor, MI (USA). Dept. of Internal Medicine)

1989-01-01

The authors evaluated the feasibility of systemic vascular perfusion with saline (mimicking plasmapheresis) as a method to enhance tumor-specific monoclonal antibody (MoAb) tumor/background ratios. Perfusion in rats dropped whole-body 5G6.4 levels significantly at both perfusion times. The drop in whole-body radioactivity with perfusion was significantly greater for the animals perfused at 4 h post i.v. 5G6.4 antibody injection (48.3 +- 5.1%) than for those perfused at 24h post i.v. antibody injection (32.9 +- 2.9%). In the nude mice with ovarian cancer xenografts, gamma camera images of tumors were visually and quantitatively by computer image analysis enhanced by perfusion, with a 2.33-fold greater decline in whole body uptake than in the tumor. These studies show that much background antibody radioactivity can be removed using whole-body perfusion with saline, that the decline in whole body activity is larger with 4 than 24h perfusion and that tumor imaging can be enhanced by this approach. This and similar approaches that increase relative tumor antibody uptake such as plasmapheresis may be useful in imaging and therapy with radiolabeled antibodies.

Contrast enhanced susceptibility weighted imaging (CE-SWI) of the mouse brain using ultrasmall superparamagnetic ironoxide particles (USPIO)

International Nuclear Information System (INIS)

Hamans, B.C.; Heerschap, A.; Barth, M.; Leenders, W.P.

2006-01-01

Susceptibility weighted imaging (SWI) has been introduced as a novel approach to visualize the venous vasculature in the human brain. With SWI, small veins in the brain are depicted based on the susceptibility difference between deoxyhaemoglobin in the veins and surrounding tissue, which is further enhanced by the use of MR phase information. In this study we applied SWI in the mouse brain using an exogenous iron-based blood-pool contrast agent, with the aims of further enhancing the susceptibility effect and allowing the visualization of individual veins and arteries. Contrast enhanced (CE-) SWI of the brain was performed on healthy mice and mice carrying intracerebral glioma xenografts. This study demonstrates that detailed vascular information in the mouse brain can be obtained by using CE-SWI and is substantially enhanced compared to native SWI (i.e. without contrast agent). CE-SWI images of tumour-bearing mice were directly compared to histology, confirming that CE-SWI depicts the vessels supplying and draining the tumour. We propose that CE-SWI is a very promising tool for the characterization of tumour vasculature. (orig.)

Cavitation-enhanced delivery of a replicating oncolytic adenovirus to tumors using focused ultrasound.

Science.gov (United States)

Bazan-Peregrino, Miriam; Rifai, Bassel; Carlisle, Robert C; Choi, James; Arvanitis, Costas D; Seymour, Leonard W; Coussios, Constantin C

2013-07-10

Oncolytic viruses (OV) and ultrasound-enhanced drug delivery are powerful novel technologies. OV selectively self-amplify and kill cancer cells but their clinical use has been restricted by limited delivery from the bloodstream into the tumor. Ultrasound has been previously exploited for targeted release of OV in vivo, but its use to induce cavitation, microbubble oscillations, for enhanced OV tumor extravasation and delivery has not been previously reported. By identifying and optimizing the underlying physical mechanism, this work demonstrates that focused ultrasound significantly enhances the delivery and biodistribution of systemically administered OV co-injected with microbubbles. Up to a fiftyfold increase in tumor transgene expression was achieved, without any observable tissue damage. Ultrasound exposure parameters were optimized as a function of tumor reperfusion time to sustain inertial cavitation, a type of microbubble activity, throughout the exposure. Passive detection of acoustic emissions during treatment confirmed inertial cavitation as the mechanism responsible for enhanced delivery and enabled real-time monitoring of successful viral delivery. Copyright © 2013 Elsevier B.V. All rights reserved.

Inhibition of IL-17A suppresses enhanced-tumor growth in low dose pre-irradiated tumor beds.

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Eun-Jung Lee

Full Text Available Ionizing radiation induces modification of the tumor microenvironment such as tumor surrounding region, which is relevant to treatment outcome after radiotherapy. In this study, the effects of pre-irradiated tumor beds on the growth of subsequently implanted tumors were investigated as well as underlying mechanism. The experimental model was set up by irradiating the right thighs of C3H/HeN mice with 5 Gy, followed by the implantation of HCa-I and MIH-2. Both implanted tumors in the pre-irradiated bed showed accelerated-growth compared to the control. Tumor-infiltrated lymphocyte (TIL levels were increased, as well as pro-tumor factors such as IL-6 and transforming growth factor-beta1 (TGF-β1 in the pre-irradiated group. In particular, the role of pro-tumor cytokine interleukin-17A (IL-17A was investigated as a possible target mechanism because IL-6 and TGF-β are key factors in Th17 cells differentiation from naïve T cells. IL-17A expression was increased not only in tumors, but also in CD4+ T cells isolated from the tumor draining lymph nodes. The effect of IL-17A on tumor growth was confirmed by treating tumors with IL-17A antibody, which abolished the acceleration of tumor growth. These results indicate that the upregulation of IL-17A seems to be a key factor for enhancing tumor growth in pre-irradiated tumor beds.

Non-palpable incidentally found testicular tumors: Differentiation between benign, malignant, and burned-out tumors using dynamic contrast-enhanced MRI

International Nuclear Information System (INIS)

Sanharawi, Imane El; Correas, Jean-Michel; Glas, Ludivine; Ferlicot, Sophie

2016-01-01

Purpose: To evaluate qualitative, semi-quantitative, and quantitative parameters obtained by dynamic contrast-enhanced (DCE)-MRI for the characterization of histologically proven, non-palpable, incidentally found intratesticular tumors. Materials and methods: From 2006 to 2014, we included men with non-palpable, incidentally found testicular tumors on ultrasound, normal tumoral marker levels,referred for surgery. DCE-MRI data were analyzed retrospectively and independently by two radiologists blinded to the histological diagnosis. The visual enhancement patterns, time-signal intensity curves, shape of the curves (type 0–3), maximal relative enhancement (Peak), initial enhancement slope (IS), time to peak (TTP), as well as transfer constants Ktrans and Kep were compared between the tumors. The interobserver correlation was evaluated. Receiver Operating Characteristic (ROC) curves and areas under the curve (AUC) were extracted. Results: Thirty-one patients (mean age of 37.3 years) were included. Tumor mean size was 1.2 ± 0.77 cm (min = 0.3 cm, max = 2.8 cm). Regarding the histology results, three groups were defined: Twelve stromal “benign tumors” (BT) exhibited more type 2 and type 3 curves than 12 “malignant tumors” (MT) and 7 “burned-out tumors” (BOT) (p < 0.0001). BT had a higher peak (96 vs. 54 and 17%), shorter TTP (215 vs. 412 and 692 sec), higher IS (73 vs. 12 and 2 arbitrary units), higher Ktrans (255 vs. 88 and 14 min −1 *1000) and higher Kep (554 vs. 159 and 48 min −1 *1000) than MT and BOT, respectively (p < 0.0001, p = 0.0003, p < 0.0001, p < 0.0001 and p < 0.0001, respectively). The agreement coefficient values and the AUC extracted after gathering MT with BOT varied from 0.83 to 0.96 and from 0.868 to 0.978, respectively. Conclusion: DCE-MRI may assist in differentiating between benign intratesticular stromal tumors,malignant and burned-out tumors.

Non-palpable incidentally found testicular tumors: Differentiation between benign, malignant, and burned-out tumors using dynamic contrast-enhanced MRI

Energy Technology Data Exchange (ETDEWEB)

Sanharawi, Imane El [Service de Radiologie Diagnostique et Interventionnelle Adulte, Groupe Hospitalier Paris Sud, Hôpital de Bicêtre, APHP, 78 avenue du Général Leclerc, 94275 Le Kremlin Bicêtre (France); Correas, Jean-Michel [Service de Radiologie Adultes, Hôpital Necker, APHP, Faculté Paris 5, 149 rue de Sèvres 75015 Paris (France); Institut Langevin, ESPCI Paris, PSL Research University CNRS UMR 7587, INSERM ERL U-979, 35, 17 rue Moreau, 75012 Paris (France); Glas, Ludivine [Service de Radiologie Diagnostique et Interventionnelle Adulte, Groupe Hospitalier Paris Sud, Hôpital de Bicêtre, APHP, 78 avenue du Général Leclerc, 94275 Le Kremlin Bicêtre (France); Ferlicot, Sophie [Service d ’ anatomo-pathologie, Groupe Hospitalier Paris Sud, Hôpital de Bicêtre, APHP, 78 avenue du Général Leclerc, 94275 Le Kremlin Bicêtre (France); Faculté de Médecine Paris-Saclay, 63 rue Gabriel Péri, 94270 Le Kremlin Bicêtre (France); and others

2016-11-15

Purpose: To evaluate qualitative, semi-quantitative, and quantitative parameters obtained by dynamic contrast-enhanced (DCE)-MRI for the characterization of histologically proven, non-palpable, incidentally found intratesticular tumors. Materials and methods: From 2006 to 2014, we included men with non-palpable, incidentally found testicular tumors on ultrasound, normal tumoral marker levels,referred for surgery. DCE-MRI data were analyzed retrospectively and independently by two radiologists blinded to the histological diagnosis. The visual enhancement patterns, time-signal intensity curves, shape of the curves (type 0–3), maximal relative enhancement (Peak), initial enhancement slope (IS), time to peak (TTP), as well as transfer constants Ktrans and Kep were compared between the tumors. The interobserver correlation was evaluated. Receiver Operating Characteristic (ROC) curves and areas under the curve (AUC) were extracted. Results: Thirty-one patients (mean age of 37.3 years) were included. Tumor mean size was 1.2 ± 0.77 cm (min = 0.3 cm, max = 2.8 cm). Regarding the histology results, three groups were defined: Twelve stromal “benign tumors” (BT) exhibited more type 2 and type 3 curves than 12 “malignant tumors” (MT) and 7 “burned-out tumors” (BOT) (p < 0.0001). BT had a higher peak (96 vs. 54 and 17%), shorter TTP (215 vs. 412 and 692 sec), higher IS (73 vs. 12 and 2 arbitrary units), higher Ktrans (255 vs. 88 and 14 min{sup −1}*1000) and higher Kep (554 vs. 159 and 48 min{sup −1}*1000) than MT and BOT, respectively (p < 0.0001, p = 0.0003, p < 0.0001, p < 0.0001 and p < 0.0001, respectively). The agreement coefficient values and the AUC extracted after gathering MT with BOT varied from 0.83 to 0.96 and from 0.868 to 0.978, respectively. Conclusion: DCE-MRI may assist in differentiating between benign intratesticular stromal tumors,malignant and burned-out tumors.

Enhanced tumor growth in the remaining lung after major lung resection.

Science.gov (United States)

Sano, Fumiho; Ueda, Kazuhiro; Murakami, Junichi; Hayashi, Masataro; Nishimoto, Arata; Hamano, Kimikazu

2016-05-01

Pneumonectomy induces active growth of the remaining lung in order to compensate for lost lung tissue. We hypothesized that tumor progression is enhanced in the activated local environment. We examined the effects of mechanical strain on the activation of lung growth and tumor progression in mice. The mechanical strain imposed on the right lung after left pneumonectomy was neutralized by filling the empty space that remained after pneumonectomy with a polypropylene prosthesis. The neutralization of the strain prevented active lung growth. According to an angiogenesis array, stronger monocyte chemoattractant protein-1 (MCP-1) expression was found in the strain-induced growing lung. The neutralization of the strain attenuated the release of MCP-1 from the lung cells. The intravenous injection of Lewis lung cancer cells resulted in the enhanced development of metastatic foci in the strain-induced growing lung, but the enhanced development was canceled by the neutralization of the strain. An immunohistochemical analysis revealed the prominent accumulation of tumor-associated macrophages in tumors arising in the strain-induced growing lung, and that there was a relationship between the accumulation and the MCP-1 expression status. Our results suggested that mechanical lung strain, induced by pulmonary resection, triggers active lung growth, thereby creating a tumor-friendly environment. The modification of that environment, as well as the minimizing of surgical stress, may be a meaningful strategy to improve the therapeutic outcome after lung cancer surgery. Copyright © 2016 Elsevier Inc. All rights reserved.

Contrast-enhanced Ultrasound for Non-tumor Liver Diseases

Directory of Open Access Journals (Sweden)

H Maruyama

2012-03-01

Full Text Available Contrast-enhanced ultrasound (CEUS is a simple, safe and reliable technique for the clinical management of patients with various liver diseases. Although the major target of the technique may be focal hepatic lesions, it is also effective for the diagnosis of non-tumor liver diseases, such as grading hepatic fibrosis, characterization of chronic liver diseases and diagnosis of portal vein thrombosis. This review article aimed to overview the recent application of CEUS in the assessment of non-tumor liver diseases. Keywords: Cirrhosis, contrast agent, fibrosis, idiopathic portal hypertension, microbubble, portal vein thrombosis, ultrasound.

Rapid bacterial antibiotic susceptibility test based on simple surface-enhanced Raman spectroscopic biomarkers

Science.gov (United States)

Liu, Chia-Ying; Han, Yin-Yi; Shih, Po-Han; Lian, Wei-Nan; Wang, Huai-Hsien; Lin, Chi-Hung; Hsueh, Po-Ren; Wang, Juen-Kai; Wang, Yuh-Lin

2016-03-01

Rapid bacterial antibiotic susceptibility test (AST) and minimum inhibitory concentration (MIC) measurement are important to help reduce the widespread misuse of antibiotics and alleviate the growing drug-resistance problem. We discovered that, when a susceptible strain of Staphylococcus aureus or Escherichia coli is exposed to an antibiotic, the intensity of specific biomarkers in its surface-enhanced Raman scattering (SERS) spectra drops evidently in two hours. The discovery has been exploited for rapid AST and MIC determination of methicillin-susceptible S. aureus and wild-type E. coli as well as clinical isolates. The results obtained by this SERS-AST method were consistent with that by the standard incubation-based method, indicating its high potential to supplement or replace existing time-consuming methods and help mitigate the challenge of drug resistance in clinical microbiology.

Micro-MRI at 11.7 T of a Murine Brain Tumor Model Using Delayed Contrast Enhancement

Directory of Open Access Journals (Sweden)

Rex A. Moats

2003-07-01

Full Text Available In vivo imaging methodologies allow for serial measurement of tumor size, circumventing the need for sacrificing mice at given time points. In orthotopically transplanted murine models of brain tumors, cross-section micro-MRI allows for visualization and measurement of the physically inaccessible tumors. To allow for long resident times of a contrast agent in the tumor, intraperitoneal administration was used as a route of injection for contrast-enhanced micro-MRI, and a simple method for relative tumor volume measurements was examined. A strategy for visualizing the variability of the delayed tumor enhancement was developed. These strategies were applied to monitor the growth of brain tumors xenotransplanted into nude mice and either treated with the antiangiogenic peptide EMD 121974 or an inactive control peptide. Each mouse was used as its own control. Serial imaging was done weekly, beginning at Day 7 after tumor cell implantation and continued for 7 weeks. Images obtained were reconstructed on the MRI instrument. The image files were transferred off line to be postprocessed to assess tumor growth (volume and variability in enhancement (three-dimensional [3-D] intensity models. In a small study, tumor growth and response to treatment were followed using this methodology and the high-resolution images displayed in 3-D allowed for straightforward qualitative assessment of variable enhancement related to vascular factors and tumor age.

Enhancement of tumor response by MEK inhibitor in murine HCa-I tumors

International Nuclear Information System (INIS)

Kim, Sung Hee; Seong, Jin Sil

2003-01-01

Extracellular signal-regulated kinase (ERK), which is part of the mitogen-activated protein kinase cascade, opposes initiation of the apoptotic cell death which is programmed by diverse cytotoxic stimuli. In this regard, the inhibition of ERK may be useful in improving the therapeutic efficacy of established anticancer agents. Murine hepatocarcinoma, HCa-l is known to be highly radioresistant with a TCD50 (radiation dose yield in 50% cure) of more than 80 Gy. Various anticancer drugs have been found to enhance the radioresponse of this particular tumor but none were successful. The objective of this study was to explore whether the selective inhibition of MEK could potentiate the antitumor efficacy of radiation in vivo, particularly in the case of radioresistant tumor. C3H/HeJ mice bearing 7.5-8 mm. HCa-l, were treated with PD98059 (intratumoral injection of 0.16 μg in 50 μl). Downregulation of ERK by PD98059 was most prominent 1h after the treatment. In the tumor growth delay assay, the drug was found to increase the effect of the tumor radioresponse with an enhancement factor (EF) of 1.6 and 1.87. Combined treatment of 25 Gy radiation with PD98059 significantly increased radiation induced apoptosis. The peak apoptotic index (number of apoptotic nuclei in 1000 nuclei X100) was 1.2% in the case of radiation treatment alone, 0.9% in the case of drug treatment alone and 4.9%, 5.3% in the combination treatment group. An analysis of apoptosis regulating molecules with Western blotting showed up regulation of p53, p21 WAF1 / CIP1 and Bcl-X s in the combination treatment group as compared to their levels in either the radiation alone or drug alone treatment groups. The level of other molecules such as Bcl-X L , Bax and BCI-2 were changed to a lesser extent. The selective inhibition of MEK in combination with radiation therapy may have potential benefit in cancer treatment

Enhancement of tumor response by MEK inhibitor in murine HCa-I tumors

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Kim, Sung Hee; Seong, Jin Sil [College of Medicine, Yonsei Univ., Seoul (Korea, Republic of)

2003-09-01

Extracellular signal-regulated kinase (ERK), which is part of the mitogen-activated protein kinase cascade, opposes initiation of the apoptotic cell death which is programmed by diverse cytotoxic stimuli. In this regard, the inhibition of ERK may be useful in improving the therapeutic efficacy of established anticancer agents. Murine hepatocarcinoma, HCa-l is known to be highly radioresistant with a TCD50 (radiation dose yield in 50% cure) of more than 80 Gy. Various anticancer drugs have been found to enhance the radioresponse of this particular tumor but none were successful. The objective of this study was to explore whether the selective inhibition of MEK could potentiate the antitumor efficacy of radiation in vivo, particularly in the case of radioresistant tumor. C3H/HeJ mice bearing 7.5-8 mm. HCa-l, were treated with PD98059 (intratumoral injection of 0.16 {mu}g in 50 {mu}l). Downregulation of ERK by PD98059 was most prominent 1h after the treatment. In the tumor growth delay assay, the drug was found to increase the effect of the tumor radioresponse with an enhancement factor (EF) of 1.6 and 1.87. Combined treatment of 25 Gy radiation with PD98059 significantly increased radiation induced apoptosis. The peak apoptotic index (number of apoptotic nuclei in 1000 nuclei X100) was 1.2% in the case of radiation treatment alone, 0.9% in the case of drug treatment alone and 4.9%, 5.3% in the combination treatment group. An analysis of apoptosis regulating molecules with Western blotting showed up regulation of p53, p21{sup WAF1}/{sup CIP1} and Bcl-X{sub s} in the combination treatment group as compared to their levels in either the radiation alone or drug alone treatment groups. The level of other molecules such as Bcl-X{sub L}, Bax and BCI-2 were changed to a lesser extent. The selective inhibition of MEK in combination with radiation therapy may have potential benefit in cancer treatment.

Transgenic Overexpression of the Proprotein Convertase Furin Enhances Skin Tumor Growth

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Jian Fu

2012-04-01

Full Text Available Furin, one of the members of the family of proprotein convertases (PCs, ubiquitously expressed as a type I membrane-bound proteinase, activates several proteins that contribute to tumor progression. In vitro studies using cancer cell lines and clinical specimens demonstrated that furin processes important substrates such as insulin-like growth factor 1 receptor (IGF-1R and transforming growth factor β, leading to increased tumor growth and progression. Despite the numerous studies associating furin with tumor development, its effects in preclinical models has not been comprehensively studied. In this study, we sought to determine the protumorigenic role of furin in vivo after a two-stage chemical carcinogenesis protocol in transgenic mice in which furin expression was targeted to the epidermal basal layer. We found that processing of the PC substrate IGF-1R and the proliferation rate of mouse epidermis was enhanced in transgenic mice when compared with their WT counterparts. Histopathologic diagnoses of the tumors demonstrated that furin transgenic mice (line F47 developed twice as many squamous carcinomas as the control, WT mice (P < .002. Similarly, tumors cells from transgenic mice were able to process PC substrates more efficiently than tumor cells from WT mice. Furthermore, furin expression resulted in a higher SCC volume in transgenic mice as well as an increase in the percentage of high-grade SCC, including poorly differentiated and spindle cell carcinomas. In conclusion, expression of furin in the basal layer of the epidermis increased tumor development and enhanced tumor growth, supporting the consideration of furin as a potential target for cancer treatment.

Tumor vessel normalization by the PI3K inhibitor HS-173 enhances drug delivery.

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Kim, Soo Jung; Jung, Kyung Hee; Son, Mi Kwon; Park, Jung Hee; Yan, Hong Hua; Fang, Zhenghuan; Kang, Yeo Wool; Han, Boreum; Lim, Joo Han; Hong, Soon-Sun

2017-09-10

Tumor vessels are leaky and immature, which causes poor oxygen and nutrient supply to tumor vessels and results in cancer cell metastasis to distant organs. This instability of tumor blood vessels also makes it difficult for anticancer drugs to penetrate and reach tumors. Numerous tumor vessel normalization approaches have been investigated for improving drug delivery into tumors. In this study, we investigated whether phosphoinositide 3-kinase (PI3K) inhibitors are able to improve vascular structure and function over the prolonged period necessary to achieve effective vessel normalization. The PI3K inhibitors, HS-173 and BEZ235 potently suppressed tumor growth and hypoxia, and increased tumor apoptosis in animal models. PI3K inhibitors also induced a regular, flat monolayer of endothelial cells (ECs) in vessels, improving stability of vessel structure, and normalized tumor vessels by increasing vascular maturity, pericyte coverage, basement membrane thickness, and tight-junctions. These effects resulted in a decrease in tumor vessel tortuosity and vessel thinning, and improved vessel function and blood flow. The tumor vessel stabilization effect of the PI3K inhibitor HS-173 also decreased the number of metastatic lung nodules in vivo metastasis model. Furthermore, HS-173 improved the delivery of doxorubicin into the tumor region, enhancing its anticancer effects. Mechanistic studies suggested that PI3K inhibitor HS-173-induced vessel normalization reflected changes in endothelial Notch signaling. Taken together, our findings indicate that vessel normalization by PI3K inhibitors restrained tumor growth and metastasis while improving chemotherapy by enhancing drug delivery into the tumor, suggesting that HS-173 may have a therapeutic value as an enhancer or an anticancer drug. Copyright © 2017 Elsevier B.V. All rights reserved.

Regulation of apoptosis by low serum in cells of different stages of neoplastic progression: enhanced susceptibility after loss of a senescence gene and decreased susceptibility after loss of a tumor suppressor gene.

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Preston, G A; Lang, J E; Maronpot, R R; Barrett, J C

1994-08-01

A cell culture model system has been used to study the susceptibility of cells to apoptotic cell death during different stages of neoplastic progression. This system consists of normal diploid Syrian hamster embryo (SHE) cells, two preneoplastic cell lines [tumor suppressor stage I (sup +I) and non-tumor suppressor stage II (sup -II)], and hamster tumor cell lines. Stage I preneoplastic cells are nontumorigenic immortal clones that suppress tumorigenicity when hybridized to tumor cells, whereas stage II cells have lost the ability to suppress tumorigenicity in cell hybrids. We refer to these two types of preneoplastic cells as sup +I and sup -II, respectively. Neoplastic progression is generally associated with cellular alterations in growth factor responsiveness. Therefore, to study the regulation of apoptosis in the system described above, cells were cultured in low serum (0.2%) as a means of withdrawing growth factors. In low serum, normal SHE cells were quiescent (labeling index of 0.2%), with little cell death. The sup +I cells showed a relatively low labeling index (1.6%) but, in contrast to the normal cells, died at a high rate (55% cell loss after 48 h) by apoptosis, as evidenced by morphology, DNA fragmentation, and in situ end-labeling of fragmented DNA. The apoptotic cells did not go through a replicative cycle while in low serum, implying that apoptosis was initiated in the G0/G1 phase of the cell cycle. The sup -II cell line showed a high labeling index (40%) after 48 h, but cell growth was balanced by cell death that occurred at approximately the same rate. The cells died, however, predominantly by necrosis. The tumor cell lines continued to proliferate in low serum, with high labeling indices (ranging from 27% to 43%) and a low level of apoptotic or necrotic cell death. To determine the relative ability of these cells to survive in vivo, normal SHE cells, sup +I cells, and sup -II cells were injected s.c. into nude mice. At 5 or 21 days after

Contrast-enhanced color Doppler ultrasound characteristics in hypervascular breast tumors: comparison with MRI

International Nuclear Information System (INIS)

Alamo, L.; Fischer, U.

2001-01-01

The aim of this study was to evaluate the accuracy of contrast-enhanced color Doppler ultrasound (CE-US) in comparison with contrast-enhanced MR imaging (CE-MRI) in the discrimination of hypervascularized breast tumors. An additional CE-US of the breast was preoperatively performed in 40 patients with a hypervascular breast lesion detected on CE-MRI. The presence of blood flow signals and the morphological characteristics of the vessels in the breast lesions were evaluated pre- and post-contrast administration, as well as the dynamic aspects of the Doppler signal, including time interval to maximum signal enhancement and persistence of the signal enhancement. Twenty-three carcinomas and 17 fibroadenomas were explored. Considering initial signal enhancement > 100 % after the administration of contrast material as a criterion suggesting malignancy, CE-MRI showed a sensitivity of 100 % and a specificity of 76.5 % in the detection of malignant breast tumors. Color Doppler signals were consistently demonstrated in all carcinomas and in 68.7 % of fibroadenomas after the administration of Levovist, with CE-US showing a sensitivity of 95.6 % and a specificity of 5.9 %. Neither the mean number of vessels per tumor, nor the location of vessels, the time to maximum increase of the Doppler signal or the persistence of signal enhancement showed significant differences between benign and malignant lesions. Additional CE-US does not increase the low specificity of MRI in patients with hypervascularized breast tumors. (orig.)

Association of dynamic susceptibility contrast enhanced MR Perfusion parameters with prognosis in elderly patients with glioblastomas

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Jabehdar Maralani, Pejman [University of Toronto, Department of Medical Imaging, Sunnybrook Health Sciences Center, Toronto, ON (Canada); Melhem, Elias R.; Herskovits, Edward H. [University of Maryland Medical Center, Department of Radiology, Baltimore, MD (United States); Wang, Sumei; Voluck, Matthew R.; Learned, Kim O.; Mohan, Suyash [Perelman School of Medicine at University of Pennsylvania, Department of Radiology, Division of Neuroradiology, Philadelphia, PA (United States); Kim, Sang Joon [University of Ulsan Asan Medical Center, Department of Radiology, Songpa-gu, Seoul (Korea, Republic of); O' Rourke, Donald M. [Perelman School of Medicine at University of Pennsylvania, Department of Surgery, Division of Neurosurgery, Philadelphia, PA (United States)

2015-09-15

We aimed to evaluate the prognostic value of dynamic susceptibility contrast (DSC) MR perfusion in elderly patients with glioblastomas (GBM). Thirty five patients aged ≥65 and 35 aged <65 years old, (referred to as elderly and younger, respectively) were included in this retrospective study. The median relative cerebral volume (rCBV) from the enhancing region (rCBV{sub ER-Med}) and immediate peritumoral region (rCBV{sub IPR-Med}) and maximum rCBV from the enhancing region of the tumor (rCBV{sub ER-Max}) were compared and correlated with survival data. Analysis was repeated after rCBVs were dichotomized into high and low values and after excluding elderly patients who did not receive postoperative chemoradiation (34.3 %). Kaplan-Meyer survival curves and parametric and semi-parametric regression tests were used for analysis. All rCBV parameters were higher in elderly compared to younger patients (p < 0.05). After adjustment for age, none were independently associated with shorter survival (p > 0.05). After rCBV dichotomization into high and low values, high rCBV in elderly was independently associated with shorter survival compared to low rCBV in elderly, or any rCBV in younger patients (p < 0.05). rCBV can be an imaging biomarker to identify a subgroup of GBM patients in the elderly with worse prognosis compared to others. (orig.)

Dual-phase contrast enhancement multi-slice CT in grading pancreatic neuroendocrine tumors

International Nuclear Information System (INIS)

Zhou Yan; Liu Jianyu; Zhu Xiang

2013-01-01

Objective: To evaluate characteristic clinical and imaging findings of pancreatic neuroendocrine tumors (NET) in dual-phase contrast enhancement MSCT. Methods: The dual-phase contrast enhancement MSCT images of 23 lesions in 20 patients with histologically confirmed pancreatic NET were studied retrospectively. Their clinical presentations, imaging characters as well as the intensities of lesions and normal pancreas in each phase were measured, and the following indices were calculated. First, the absolute enhancement of lesions, including the increasing of CT value of the maximum enhancement area within a tumor in arterial phase, that was named A1 in short, and that of the minimum enhancement area was labeled as A2. The same ROI measured increasing CT values in portal venous phase was labeled as V1 and V2 respectively. Secondly, the relatively enhancement indices comparing with the normal pancreas in the same patient within the same phase were calculated. This included the differences between the maximum, as well as the minimum, enhancement areas of tumors and the normal pancreas in arterial phase, which was named as AP1 and AP2 respectively, and those differences in portal venous phase, which were labeled as VP1 and VP2 respectively. All of the tumors were graded as G1 to G3 according to the WHO classification in 2010. A Kruskal Wallis test were performed to compare differences of tumor diameters and the enhancement indices. The change trend of enhancement indices varying with pathology grading were described. Fisher exact test was used to find differences of clinical and imaging characters. Results: Twenty-three lesions in 20 patients included 13 lesions in grade 1 (G1), 8 in G2, and 2 in G3. Among the 10 patients with G1 NET, 7 of them had no endocrine symptoms, while the other 3 had endocrine symptoms. Six of them had no abdominal pain, while 4 of them complained of it. All of the 10 patients with G1 NET had no hepatic metastasis. Among 8 patients with G2 NET

Comparison of Oral Contrast-Enhanced Transabdominal Ultrasound Imaging With Transverse Contrast-Enhanced Computed Tomography in Preoperative Tumor Staging of Advanced Gastric Carcinoma.

Science.gov (United States)

He, Xuemei; Sun, Jing; Huang, Xiaoling; Zeng, Chun; Ge, Yinggang; Zhang, Jun; Wu, Jingxian

2017-12-01

This study assessed the diagnostic performance of transabdominal oral contrast-enhanced ultrasound (US) imaging for preoperative tumor staging of advanced gastric carcinoma by comparing it with transverse contrast-enhanced computed tomography (CT). This retrospective study included 42 patients with advanced gastric cancer who underwent laparoscopy, radical surgery, or palliative surgery because of serious complications and had a body mass index of less than 25 kg/m 2 . A cereal-based oral contrast agent was used for transabdominal oral contrast-enhanced US. Retrospective analyses were conducted using preoperative tumor staging data acquired by either transabdominal oral contrast-enhanced US or transverse contrast-enhanced CT. Both contrast-enhanced US and contrast-enhanced CT examinations were reviewed by 2 experienced radiologists independently for preoperative tumor staging according to the seventh edition of the TNM classification. The accuracy, sensitivity, and specificity were calculated by comparing the results of contrast-enhanced US and contrast-enhanced CT with pathologic findings. The overall accuracies of the imaging modalities were compared by the McNemar test. No significant difference was noted in the overall accuracy of transabdominal oral contrast-enhanced US (86% [36 of 42]) and transverse contrast-enhanced CT (83% [35 of 42] P > .999). For stage T2 to T4 gastric cancer, the accuracies of transabdominal oral contrast-enhanced US were 88%, 86%, and 98%, respectively, and those of transverse contrast-enhanced CT were 93%, 83%, and 90%. The overall accuracy of transabdominal oral contrast-enhanced US was comparable with that of transverse contrast-enhanced CT for preoperative tumor staging of advanced gastric cancer. © 2017 by the American Institute of Ultrasound in Medicine.

Differentiation between tuberculosis and primary tumors in the adrenal gland: evaluation with contrast-enhanced CT

International Nuclear Information System (INIS)

Yang, Zhi-Gang; Guo, Ying-Kun; Li, Yuan; Min, Peng-Qiu; Yu, Jian-Qun; Ma, En-Sen

2006-01-01

The aim of the present study is to determine imaging criteria for differentiating tuberculosis from primary tumors in the adrenal gland on contrast-enhanced CT. Non-contrast and contrast-enhanced CT features in 108 patients with adrenal tuberculosis (n=34) and primary tumor (n=74) were retrospectively assessed for the location, size, calcification and enhancement patterns. The primary tumors included 41 adenomas, 11 pheochromocytomas, 4 carcinomas, 3 lymphomas, 6 myelolipomas, 6 ganglioneuromas, 2 neurilemmomas and 1 ganglioneuroblastoma. Biochemical investigation was performed for all patients. Of the tuberculosis cases, 31 (91%) invaded with bilateral involvement, while 7 (9%) of the primary tumors invaded with bilateral involvement (P<0.001). Tuberculosis often showed calcification (20 of 34; 59%), whereas primary tumors infrequently showed calcification (6 of 74; 8%; P<0.001). Low attenuation in the center with peripheral rim enhancement was more commonly seen in tuberculosis (16 of 34; 47%) than in primary tumors (7 of 74; 9%; P<0.001). In the determination of tuberculosis, the highest sensitivity (91%) and accuracy (91%) were obtained with bilateral involvement, and the highest specificity (99%) was obtained with the contour preserved. In the determination of primary tumors using a combination of having unilateral involvement and being mass-like, the outcome was a sensitivity of 91%, specificity of 94% and accuracy of 92%. CT findings can differentiate tuberculosis from a primary tumor of the adrenal glands with high sensitivity and an acceptable specificity when combined with the endocrinological examination. (orig.)

Assessment of contrast enhanced respiration managed cone-beam CT for image guided radiotherapy of intrahepatic tumors

International Nuclear Information System (INIS)

Jensen, Nikolaj K. G.; Stewart, Errol; Lock, Michael; Fisher, Barbara; Kozak, Roman; Chen, Jeff; Lee, Ting-Yim; Wong, Eugene

2014-01-01

Purpose: Contrast enhancement and respiration management are widely used during image acquisition for radiotherapy treatment planning of liver tumors along with respiration management at the treatment unit. However, neither respiration management nor intravenous contrast is commonly used during cone-beam CT (CBCT) image acquisition for alignment prior to radiotherapy. In this study, the authors investigate the potential gains of injecting an iodinated contrast agent in combination with respiration management during CBCT acquisition for liver tumor radiotherapy. Methods: Five rabbits with implanted liver tumors were subjected to CBCT with and without motion management and contrast injection. The acquired CBCT images were registered to the planning CT to determine alignment accuracy and dosimetric impact. The authors developed a simulation tool for simulating contrast-enhanced CBCT images from dynamic contrast enhanced CT imaging (DCE-CT) to determine optimal contrast injection protocols. The tool was validated against contrast-enhanced CBCT of the rabbit subjects and was used for five human patients diagnosed with hepatocellular carcinoma. Results: In the rabbit experiment, when neither motion management nor contrast was used, tumor centroid misalignment between planning image and CBCT was 9.2 mm. This was reduced to 2.8 mm when both techniques were employed. Tumors were not visualized in clinical CBCT images of human subjects. Simulated contrast-enhanced CBCT was found to improve tumor contrast in all subjects. Different patients were found to require different contrast injections to maximize tumor contrast. Conclusions: Based on the authors’ animal study, respiration managed contrast enhanced CBCT improves IGRT significantly. Contrast enhanced CBCT benefits from patient specific tracer kinetics determined from DCE-CT

Assessment of contrast enhanced respiration managed cone-beam CT for image guided radiotherapy of intrahepatic tumors

Energy Technology Data Exchange (ETDEWEB)

Jensen, Nikolaj K. G., E-mail: nkyj@regionsjaelland.dk [Physics and Engineering, London Regional Cancer Program, London, Ontario N6A3K7 (Canada); Stewart, Errol [Radiology, St. Joseph' s Health Care, London, Ontario N6A 4V2 (Canada); Imaging Research Lab, Robarts Research Institute, London, Ontario N6A 5B7 (Canada); Imaging Program, Lawson Health Research Institute, London, Ontario N6C 2R5 (Canada); Lock, Michael; Fisher, Barbara [Radiation Oncology, London Regional Cancer Program, London, Ontario N6A3K7 (Canada); Department of Oncology, University of Western Ontario, London, Ontario N6A 4L6 (Canada); Kozak, Roman [Radiology, St. Joseph' s Health Care, London, Ontario N6A 4V2 (Canada); Chen, Jeff [Physics and Engineering, London Regional Cancer Program, London, Ontario N6A3K7 (Canada); Department of Oncology, University of Western Ontario, London, Ontario N6A 4L6 (Canada); Department of Medical Biophysics, University of Western Ontario, London, Ontario N6A 5C1 (Canada); Lee, Ting-Yim [Radiology, St. Joseph' s Health Care, London, Ontario N6A 4V2 (Canada); Imaging Research Lab, Robarts Research Institute, London, Ontario N6A 5B7 (Canada); Imaging Program, Lawson Health Research Institute, London, Ontario N6C 2R5 (Canada); Department of Oncology, University of Western Ontario, London, Ontario N6A 4L6 (Canada); Department of Medical Biophysics, University of Western Ontario, London, Ontario N6A 5C1 (Canada); Wong, Eugene [Physics and Engineering, London Regional Cancer Program, London, Ontario N6A3K7 (Canada); Department of Oncology, University of Western Ontario, London, Ontario N6A 4L6 (Canada); Department of Medical Biophysics, University of Western Ontario, London, Ontario N6A 5C1 (Canada); Department of Physics and Astronomy, University of Western Ontario, London, Ontario N6A 3K7 (Canada)

2014-05-15

Purpose: Contrast enhancement and respiration management are widely used during image acquisition for radiotherapy treatment planning of liver tumors along with respiration management at the treatment unit. However, neither respiration management nor intravenous contrast is commonly used during cone-beam CT (CBCT) image acquisition for alignment prior to radiotherapy. In this study, the authors investigate the potential gains of injecting an iodinated contrast agent in combination with respiration management during CBCT acquisition for liver tumor radiotherapy. Methods: Five rabbits with implanted liver tumors were subjected to CBCT with and without motion management and contrast injection. The acquired CBCT images were registered to the planning CT to determine alignment accuracy and dosimetric impact. The authors developed a simulation tool for simulating contrast-enhanced CBCT images from dynamic contrast enhanced CT imaging (DCE-CT) to determine optimal contrast injection protocols. The tool was validated against contrast-enhanced CBCT of the rabbit subjects and was used for five human patients diagnosed with hepatocellular carcinoma. Results: In the rabbit experiment, when neither motion management nor contrast was used, tumor centroid misalignment between planning image and CBCT was 9.2 mm. This was reduced to 2.8 mm when both techniques were employed. Tumors were not visualized in clinical CBCT images of human subjects. Simulated contrast-enhanced CBCT was found to improve tumor contrast in all subjects. Different patients were found to require different contrast injections to maximize tumor contrast. Conclusions: Based on the authors’ animal study, respiration managed contrast enhanced CBCT improves IGRT significantly. Contrast enhanced CBCT benefits from patient specific tracer kinetics determined from DCE-CT.

The role of contrast-enhanced digital subtraction MRI in the diagnosis of vertebral metastasic tumors

International Nuclear Information System (INIS)

Xiao Yeyu; Yang Jun; Qi Weili; Liu Qize; Hong Bikai; Wu Renhua

2008-01-01

Objective: To evaluate the contrast-enhanced digital subtraction MRI in the diagnosis of vertebral metastasic tumors. Methods 66 vertebral metastasic tumors in 43 patients were examined with conventional MRI (T 1 WI, STIR and Contrast-enhanced T 1 WI) and contrast-enhanced digital subtraction MR imaging. All lesions were histologically proved. The quantity and characteristic imaging signs (including spiculation, bull eye sign and irregular edge) of lesions were detected separately by different sequences. K independent samples test was used. Results: The detection rates of 35 vertebral metastasic tumors with vertebral morphological changes were same in all MR sequences. But in the other 31 lesions without vertebral morphological changes, the detection rates were different and STIR was the highest in all sequences. Contrast-enhanced digital subtraction MRI was more sensitive than all the conventional MR sequences in finding characteristic imaging signs with statistically significant differences. Conclusion: Contrast enhanced subtraction MRI is an useful and convenient technique which has great value in finding vertebral metastasic tumors and depicting the characteristic imaging signs. (authors)

Intravenous contrast-enhanced cone beam computed tomography (IVCBCT of intrahepatic tumors and vessels

Directory of Open Access Journals (Sweden)

Cynthia L. Eccles, BSc

2016-01-01

Conclusions: Intravenous-CBCT may enhance the visibility of hepatic vessels and tumor in CBCT scans obtained during breath hold. Optimization of IV contrast timing and reduction of artifacts to improve tumor visualization warrant further investigation.

STrategically Acquired Gradient Echo (STAGE) imaging, part I: Creating enhanced T1 contrast and standardized susceptibility weighted imaging and quantitative susceptibility mapping.

Science.gov (United States)

Chen, Yongsheng; Liu, Saifeng; Wang, Yu; Kang, Yan; Haacke, E Mark

2018-02-01

To provide whole brain grey matter (GM) to white matter (WM) contrast enhanced T1W (T1WE) images, multi-echo quantitative susceptibility mapping (QSM), proton density (PD) weighted images, T1 maps, PD maps, susceptibility weighted imaging (SWI), and R2* maps with minimal misregistration in scanning times creating enhanced GM/WM contrast (the T1WE). The proposed T1WE image was created from a combination of the proton density weighted (6°, PDW) and T1W (24°) images and corrected for RF transmit field variations. Prior to the QSM calculation, a multi-echo phase unwrapping strategy was implemented using the unwrapped short echo to unwrap the longer echo to speed up computation. R2* maps were used to mask deep grey matter and veins during the iterative QSM calculation. A weighted-average sum of susceptibility maps was generated to increase the signal-to-noise ratio (SNR) and the contrast-to-noise ratio (CNR). The proposed T1WE image has a significantly improved CNR both for WM to deep GM and WM to cortical GM compared to the acquired T1W image (the first echo of 24° scan) and the T1MPRAGE image. The weighted-average susceptibility maps have 80±26%, 55±22%, 108±33% SNR increases across the ten subjects compared to the single echo result of 17.5ms for the putamen, caudate nucleus, and globus pallidus, respectively. STAGE imaging offers the potential to create a standardized brain imaging protocol providing four pieces of quantitative tissue property information and multiple types of qualitative information in just 5min. Published by Elsevier Inc.

Pyruvate induces transient tumor hypoxia by enhancing mitochondrial oxygen consumption and potentiates the anti-tumor effect of a hypoxia-activated prodrug TH-302.

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Yoichi Takakusagi

Full Text Available BACKGROUND: TH-302 is a hypoxia-activated prodrug (HAP of bromo isophosphoramide mustard that is selectively activated within hypoxic regions in solid tumors. Our recent study showed that intravenously administered bolus pyruvate can transiently induce hypoxia in tumors. We investigated the mechanism underlying the induction of transient hypoxia and the combination use of pyruvate to potentiate the anti-tumor effect of TH-302. METHODOLOGY/RESULTS: The hypoxia-dependent cytotoxicity of TH-302 was evaluated by a viability assay in murine SCCVII and human HT29 cells. Modulation in cellular oxygen consumption and in vivo tumor oxygenation by the pyruvate treatment was monitored by extracellular flux analysis and electron paramagnetic resonance (EPR oxygen imaging, respectively. The enhancement of the anti-tumor effect of TH-302 by pyruvate treatment was evaluated by monitoring the growth suppression of the tumor xenografts inoculated subcutaneously in mice. TH-302 preferentially inhibited the growth of both SCCVII and HT29 cells under hypoxic conditions (0.1% O2, with minimal effect under aerobic conditions (21% O2. Basal oxygen consumption rates increased after the pyruvate treatment in SCCVII cells in a concentration-dependent manner, suggesting that pyruvate enhances the mitochondrial respiration to consume excess cellular oxygen. In vivo EPR oxygen imaging showed that the intravenous administration of pyruvate globally induced the transient hypoxia 30 min after the injection in SCCVII and HT29 tumors at the size of 500-1500 mm(3. Pretreatment of SCCVII tumor bearing mice with pyruvate 30 min prior to TH-302 administration, initiated with small tumors (∼ 550 mm(3, significantly delayed tumor growth. CONCLUSIONS/SIGNIFICANCE: Our in vitro and in vivo studies showed that pyruvate induces transient hypoxia by enhancing mitochondrial oxygen consumption in tumor cells. TH-302 therapy can be potentiated by pyruvate pretreatment if started at the

Pyruvate induces transient tumor hypoxia by enhancing mitochondrial oxygen consumption and potentiates the anti-tumor effect of a hypoxia-activated prodrug TH-302.

Science.gov (United States)

Takakusagi, Yoichi; Matsumoto, Shingo; Saito, Keita; Matsuo, Masayuki; Kishimoto, Shun; Wojtkowiak, Jonathan W; DeGraff, William; Kesarwala, Aparna H; Choudhuri, Rajani; Devasahayam, Nallathamby; Subramanian, Sankaran; Munasinghe, Jeeva P; Gillies, Robert J; Mitchell, James B; Hart, Charles P; Krishna, Murali C

2014-01-01

TH-302 is a hypoxia-activated prodrug (HAP) of bromo isophosphoramide mustard that is selectively activated within hypoxic regions in solid tumors. Our recent study showed that intravenously administered bolus pyruvate can transiently induce hypoxia in tumors. We investigated the mechanism underlying the induction of transient hypoxia and the combination use of pyruvate to potentiate the anti-tumor effect of TH-302. The hypoxia-dependent cytotoxicity of TH-302 was evaluated by a viability assay in murine SCCVII and human HT29 cells. Modulation in cellular oxygen consumption and in vivo tumor oxygenation by the pyruvate treatment was monitored by extracellular flux analysis and electron paramagnetic resonance (EPR) oxygen imaging, respectively. The enhancement of the anti-tumor effect of TH-302 by pyruvate treatment was evaluated by monitoring the growth suppression of the tumor xenografts inoculated subcutaneously in mice. TH-302 preferentially inhibited the growth of both SCCVII and HT29 cells under hypoxic conditions (0.1% O2), with minimal effect under aerobic conditions (21% O2). Basal oxygen consumption rates increased after the pyruvate treatment in SCCVII cells in a concentration-dependent manner, suggesting that pyruvate enhances the mitochondrial respiration to consume excess cellular oxygen. In vivo EPR oxygen imaging showed that the intravenous administration of pyruvate globally induced the transient hypoxia 30 min after the injection in SCCVII and HT29 tumors at the size of 500-1500 mm(3). Pretreatment of SCCVII tumor bearing mice with pyruvate 30 min prior to TH-302 administration, initiated with small tumors (∼ 550 mm(3)), significantly delayed tumor growth. Our in vitro and in vivo studies showed that pyruvate induces transient hypoxia by enhancing mitochondrial oxygen consumption in tumor cells. TH-302 therapy can be potentiated by pyruvate pretreatment if started at the appropriate tumor size and oxygen concentration.

GM-CSF enhances tumor invasion by elevated MMP-2, -9, and -26 expression

International Nuclear Information System (INIS)

Gutschalk, Claudia M; Yanamandra, Archana K; Linde, Nina; Meides, Alice; Depner, Sofia; Mueller, Margareta M

2013-01-01

Granulocyte–macrophage colony-stimulating factor (GM-CSF) promotes tumor progression in different tumor models in an autocrine and paracrine manner. However, at the same time GM-CSF is used in cancer therapies to ameliorate neutropenia. We have previously shown in GM-CSF and G-CSF expressing or negative skin or head and neck squamous cell carcinoma that GM-CSF expression is associated with a highly angiogenic and invasive tumor phenotype. To determine the functional contribution of GM-CSF to tumor invasion, we stably transfected a GM-CSF negative colon adenocarcinoma cell line HT-29 with GM-CSF or treated the same cell line with exogenous GM-CSF. While GM-CSF overexpression and treatment reduced tumor cell proliferation and tumor growth in vitro and in vivo, respectively, it contributed to tumor progression. Together with an enhanced migratory capacity in vitro, we observed a striking increase in tumor cell invasion into the surrounding tissue concomitant with the induction of an activated tumor stroma in GM-CSF overexpressing or GM-CSF treated tumors. In a complex 3D in vitro model, enhanced GM-CSF expression was associated with a discontinued basement membrane deposition that might be mediated by the increased expression and activation of MMP-2, -9, and -26. Treatment with GM-CSF blocking antibodies reversed this effect. The increased presence and activity of these tumor cell derived proteases was confirmed in vivo. Here, expression of MMP-26 protein was predominantly located in pre- and early-invasive areas suggesting MMP-26 expression as an early event in promoting GM-CSF dependent tumor invasion

Applying gold nanoparticles as tumor-vascular disrupting agents during brachytherapy: estimation of endothelial dose enhancement

International Nuclear Information System (INIS)

Ngwa, Wilfred; Makrigiorgos, G Mike; Berbeco, Ross I

2010-01-01

Tumor vascular disrupting agents (VDAs) represent a promising approach to the treatment of cancer, in view of the tumor vasculature's pivotal role in tumor survival, growth and metastasis. VDAs targeting the tumor's dysmorphic endothelial cells can cause selective and rapid occlusion of the tumor vasculature, leading to tumor cell death from ischemia and extensive hemorrhagic necrosis. In this study, the potential for applying gold nanoparticles (AuNPs) as VDAs, during brachytherapy, is examined. Analytic calculations based on the electron energy loss formula of Cole were carried out to estimate the endothelial dose enhancement caused by radiation-induced photo/Auger electrons originating from AuNPs targeting the tumor endothelium. The endothelial dose enhancement factor (EDEF), representing the ratio of the dose to the endothelium with and without gold nanoparticles was calculated for different AuNP local concentrations, and endothelial cell thicknesses. Four brachytherapy sources were investigated, I-125, Pd-103, Yb-169, as well as 50 kVp x-rays. The results reveal that, even at relatively low intra-vascular AuNP concentrations, ablative dose enhancement to tumor endothelial cells due to photo/Auger electrons from the AuNPs can be achieved. Pd-103 registered the highest EDEF values of 7.4-271.5 for local AuNP concentrations ranging from 7 to 350 mg g -1 , respectively. Over the same concentration range, I-125, 50 kVp and Yb-169 yielded values of 6.4-219.9, 6.3-214.5 and 4.0-99.7, respectively. Calculations of the EDEF as a function of endothelial cell thickness showed that lower energy sources like Pd-103 reach the maximum EDEF at smaller thicknesses. The results also reveal that the highest contribution to the EDEF comes from Auger electrons, apparently due to their shorter range. Overall, the data suggest that ablative dose enhancement to tumor endothelial cells can be achieved by applying tumor vasculature-targeted AuNPs as adjuvants to brachytherapy, with

Applying gold nanoparticles as tumor-vascular disrupting agents during brachytherapy: estimation of endothelial dose enhancement

Science.gov (United States)

Ngwa, Wilfred; Makrigiorgos, G. Mike; Berbeco, Ross I.

2010-11-01

Tumor vascular disrupting agents (VDAs) represent a promising approach to the treatment of cancer, in view of the tumor vasculature's pivotal role in tumor survival, growth and metastasis. VDAs targeting the tumor's dysmorphic endothelial cells can cause selective and rapid occlusion of the tumor vasculature, leading to tumor cell death from ischemia and extensive hemorrhagic necrosis. In this study, the potential for applying gold nanoparticles (AuNPs) as VDAs, during brachytherapy, is examined. Analytic calculations based on the electron energy loss formula of Cole were carried out to estimate the endothelial dose enhancement caused by radiation-induced photo/Auger electrons originating from AuNPs targeting the tumor endothelium. The endothelial dose enhancement factor (EDEF), representing the ratio of the dose to the endothelium with and without gold nanoparticles was calculated for different AuNP local concentrations, and endothelial cell thicknesses. Four brachytherapy sources were investigated, I-125, Pd-103, Yb-169, as well as 50 kVp x-rays. The results reveal that, even at relatively low intra-vascular AuNP concentrations, ablative dose enhancement to tumor endothelial cells due to photo/Auger electrons from the AuNPs can be achieved. Pd-103 registered the highest EDEF values of 7.4-271.5 for local AuNP concentrations ranging from 7 to 350 mg g-1, respectively. Over the same concentration range, I-125, 50 kVp and Yb-169 yielded values of 6.4-219.9, 6.3-214.5 and 4.0-99.7, respectively. Calculations of the EDEF as a function of endothelial cell thickness showed that lower energy sources like Pd-103 reach the maximum EDEF at smaller thicknesses. The results also reveal that the highest contribution to the EDEF comes from Auger electrons, apparently due to their shorter range. Overall, the data suggest that ablative dose enhancement to tumor endothelial cells can be achieved by applying tumor vasculature-targeted AuNPs as adjuvants to brachytherapy, with lower

Residual tumor cells that drive disease relapse after chemotherapy do not have enhanced tumor initiating capacity.

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Ganapati V Hegde

Full Text Available Although chemotherapy is used to treat most advanced solid tumors, recurrent disease is still the major cause of cancer-related mortality. Cancer stem cells (CSCs have been the focus of intense research in recent years because they provide a possible explanation for disease relapse. However, the precise role of CSCs in recurrent disease remains poorly understood and surprisingly little attention has been focused on studying the cells responsible for re-initiating tumor growth within the original host after chemotherapy treatment. We utilized both xenograft and genetically engineered mouse models of non-small cell lung cancer (NSCLC to characterize the residual tumor cells that survive chemotherapy treatment and go on to cause tumor regrowth, which we refer to as tumor re-initiating cells (TRICs. We set out to determine whether TRICs display characteristics of CSCs, and whether assays used to define CSCs also provide an accurate readout of a cell's ability to cause tumor recurrence. We did not find consistent enrichment of CSC marker positive cells or enhanced tumor initiating potential in TRICs. However, TRICs from all models do appear to be in EMT, a state that has been linked to chemoresistance in numerous types of cancer. Thus, the standard CSC assays may not accurately reflect a cell's ability to drive disease recurrence.

AKT-mediated enhanced aerobic glycolysis causes acquired radioresistance by human tumor cells

International Nuclear Information System (INIS)

Shimura, Tsutomu; Noma, Naoto; Sano, Yui; Ochiai, Yasushi; Oikawa, Toshiyuki; Fukumoto, Manabu; Kunugita, Naoki

2014-01-01

Background and purpose: Cellular radioresistance is a major impediment to effective radiotherapy. Here, we demonstrated that long-term exposure to fractionated radiation conferred acquired radioresistance to tumor cells due to AKT-mediated enhanced aerobic glycolysis. Material and methods: Two human tumor cell lines with acquired radioresistance were established by long-term exposure to fractionated radiation with 0.5 Gy of X-rays. Glucose uptake was inhibited using 2-deoxy-D-glucose, a non-metabolizable glucose analog. Aerobic glycolysis was assessed by measuring lactate concentrations. Cells were then used for assays of ROS generation, survival, and cell death as assessed by annexin V staining. Results: Enhanced aerobic glycolysis was shown by increased glucose transporter Glut1 expression and a high lactate production rate in acquired radioresistant cells compared with parental cells. Inhibiting the AKT pathway using the AKT inhibitor API-2 abrogated these phenomena. Moreover, we found that inhibiting glycolysis with 2-deoxy-D-glucose suppressed acquired tumor cell radioresistance. Conclusions: Long-term fractionated radiation confers acquired radioresistance to tumor cells by AKT-mediated alterations in their glucose metabolic pathway. Thus, tumor cell metabolic pathway is an attractive target to eliminate radioresistant cells and improve radiotherapy efficacy

HemoHIM enhances the therapeutic efficacy of ionizing radiation treatment in tumor-bearing mice.

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Park, Hae-Ran; Ju, Eun-Jin; Jo, Sung-Kee; Jung, Uhee; Kim, Sung-Ho

2010-02-01

Although radiotherapy is commonly used for a variety of cancers, radiotherapy alone does not achieve a satisfactory therapeutic outcome. In this study, we examined the possibility that HemoHIM can enhance the anticancer effects of ionizing radiation (IR) in melanoma-bearing mice. The HemoHIM was prepared by adding the ethanol-insoluble fraction to the total water extract of a mixture of three edible herbs-Angelica Radix, Cnidium Rhizoma, and Paeonia Radix. Anticancer effects of HemoHIM were evaluated in melanoma-bearing mice exposed to IR. IR treatment (5 Gy at 7 days after melanoma cell injection) reduced the weight of the solid tumors, and HemoHIM supplementation with IR enhanced the decreases in tumor weight (P HemoHIM administration also increased the activity of natural killer cells and cytotoxic T cells, although the proportions of these cells in spleen were not different. In addition, HemoHIM administration increased the interleukin-2 and tumor necrosis factor-alpha secretion from lymphocytes stimulated with concanavalin A, which seemed to contribute to the enhanced efficacy of HemoHIM in tumor-bearing mice treated with IR. In conclusion, HemoHIM may be a beneficial supplement during radiotherapy for enhancing the antitumor efficacy.

Polymorphisms in tumor necrosis factor genes and susceptibility to visceral leishmaniasis in Moroccan children

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Rajaa Ejghal

2015-05-01

Full Text Available Objective: To examine whether polymorphic alleles at these two loci are involved in the susceptibility to visceral leishmaniasis (VL in Moroccan children. Methods: We have genotyped polymorphisms by PCR-restricted fragment length polymorphisms in 102 patients with VL, 92 asymptomatic carriers [positive skin test delayedtype hypersensitivity (DTH+] and 40 healthy controls (negative skin test delayed-type hypersensitivity, with no history of Leishmania infection. Results: Regression analysis showed no significant association between polymorphisms of tumor necrosis factors-ααwhen comparing VL and DTH + group (P > 0.05. The associations were detected between VL and negative skin test delayed-type hypersensitivity for the heterozygote genotype (P = 0.021, the recessive model: 1/2 + 2/2 (P = 0.044 and the minor allele 2 (P = 0.019. The resistance to VL was found to be under the recessive model 1/2 + 2/2 of tumor necrosis factors-β, when comparing VL and DTH + group (odds ratios: 0.558, 95%; confidence interval: 0.316-0.987; P = 0.044. Conclusions: These results must be regarded to preliminary but suggestive that further study with larger populations is worthwhile.

Evaluation of the MRI with Gd-DTPA enhancement in the diagnosis of brain and spinal tumors

Energy Technology Data Exchange (ETDEWEB)

Fukui, Keiji; Sadamoto, Kazuhiko; Miki, Hitoshi; Sakaki, Saburo; Matsuoka, Kenzo.

1988-02-01

Magnetic resonance (MR) imaging was performed using saturation recovery (SR), inversion recovery (IR) and spin echo (SE) pulse sequences before and after the injection of 0.1 mmol of gadolinium diethylenetriamine pentaacetic acid dimeglumine (Gd-DTPA) per kilogram of body weight. Forty-two patients with gliomas (8), meningiomas (12), neurinomas (5), adenoma (1), craniopharyngioma (1), chordoma (1), malignant lymphomas (2), metastatic brain tumors (2), spinal tumors (4), and other tumors (6) were studied. Contrast enhancement was shown in 35 of the 38 patients with brain tumors and in all those with spinal tumors on T/sub 1/-weighted images. The T/sub 1/ relaxation time was decreased in all of these 39 tumors, while the T/sub 2/ relaxation time showed no definite tendency. No marked side effects were observed following the administration of Gd-DTPA. By using Gd-DTPA enhancement, it was possible to differentiate the tumor from the peritumoral edema on MRI, although it was difficult to do so on precontrast MRI. Among the various pulse sequences, the SR sequence provides the best diagnostic value with Gd-DTPA enhancement in the shortest examination time for screening brain and spinal tumors.

Enhancement in blood-tumor barrier permeability and delivery of liposomal doxorubicin using focused ultrasound and microbubbles: evaluation during tumor progression in a rat glioma model

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Aryal, Muna; Park, Juyoung; Vykhodtseva, Natalia; Zhang, Yong-Zhi; McDannold, Nathan

2015-03-01

Effective drug delivery to brain tumors is often challenging because of the heterogeneous permeability of the ‘blood tumor barrier’ (BTB) along with other factors such as increased interstitial pressure and drug efflux pumps. Focused ultrasound (FUS) combined with microbubbles can enhance the permeability of the BTB in brain tumors, as well as the blood-brain barrier in the surrounding tissue. In this study, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was used to characterize the FUS-induced permeability changes of the BTB in a rat glioma model at different times after implantation. 9L gliosarcoma cells were implanted in both hemispheres in male rats. At day 9, 14, or 17 days after implantation, FUS-induced BTB disruption using 690 kHz ultrasound and definity microbubbles was performed in one tumor in each animal. Before FUS, liposomal doxorubicin was administered at a dose of 5.67 mg kg-1. This chemotherapy agent was previously shown to improve survival in animal glioma models. The transfer coefficient Ktrans describing extravasation of the MRI contrast agent Gd-DTPA was measured via DCE-MRI before and after sonication. We found that tumor doxorubicin concentrations increased monotonically (823  ±  600, 1817  ±  732 and 2432  ±  448 ng g-1) in the control tumors at 9, 14 and 17 d. With FUS-induced BTB disruption, the doxorubicin concentrations were enhanced significantly (P benefit from FUS-induced drug enhancement. Corresponding enhancements in Ktrans were found to be variable in large/late-stage tumors and not significantly different than controls, perhaps reflecting the size mismatch between the liposomal drug (~100 nm) and Gd-DTPA (molecular weight: 938 Da; hydrodynamic diameter: ≃2 nm). It may be necessary to use a larger MRI contrast agent to effectively evaluate the sonication-induced enhanced permeabilization in large/late-stage tumors when a large drug carrier such as a liposome is used.

Difluoromethylornithine enhanced uptake of tritiated putrescine in 9L rat brain tumors

International Nuclear Information System (INIS)

Redgate, E.S.; Grudziak, A.G.; Deutsch, M.; Boggs, S.S.

1997-01-01

Difluoromethylornithine (DFMO) depletes endogenous putrescine and enhances the uptake of and retention of [ 3 H] putrescine in vitro. To determine if DFMO also enhances uptake of [ 3 H] putrescine in vivo, DFMO and trace doses of [ 3 H] putrescine, dissolved in artificial CSF, were infused into growing (6-9 day) 9L brain tumors by means of osmotic pumps. When 7-day osmotic pumps were loaded with 1 μCi [ 3 H] putrescine, with or without 10 or 100 mM DFMO, pumped at 1 μl/h, the mean uptake after 3 days was 168 ± 62 cpm/mg tumor (17 rats) without DFMO, 300 ± 197 cpm/mg tumor (11 rats) with 10 mM DFMO and 1088 ± 421 cpm/mg tumor (11 rats) with 100 mM DFMO (p ≤ 0.05 vs. control). Significantly less radioactivity was detected in the contralateral brain and in nonbrain tissues (0.5 ± 0.1 to 14 ± 5 cpm/mg). To measure the extent of [ 3 H] putrescine distribution in the tumor, the same dose of drugs was delivered for a longer period of time, using 14-day pumps to allow tumors to become large enough to be divided into 1.4 mm thick transections. The mean radioactivity in the sections from eight control rats receiving [ 3 H] putrescine without DFMO were not significantly different between the sections (174 ± 61 cpm/mg tumor for sections containing the cannulas, 273 ± 61 and 259 ± 91 cpm/mg for adjacent sections). In the six rats given 100 mM DFMO there was a significant increase in mean radioactivity in the cannula containing section (2251 ± 919 cpm/mg tumor). Mean counts from adjacent sections in these rats were 97 ± 44 and 33 ± 13 cpm/mg. Values for contralateral corpus striatum and nonbrain tissues ranged from 0.7 ± 0.3 to 4.3 ± 1.5 cpm/mg tissue. When DFMO was delivered directly to the tumors while [ 3 H] putrescine was infused intraperitoneally, the uptake in the tumor slices was low (5-10 cpm/mg in different slices). These results demonstrate that infusion of DFMO directly into growing 9L brain tumors can selectively enhance the uptake of exogenous [ 3 H

Effect of contrast leakage on the detection of abnormal brain tumor vasculature in high-grade glioma.

Science.gov (United States)

LaViolette, Peter S; Daun, Mitchell K; Paulson, Eric S; Schmainda, Kathleen M

2014-02-01

Abnormal brain tumor vasculature has recently been highlighted by a dynamic susceptibility contrast (DSC) MRI processing technique. The technique uses independent component analysis (ICA) to separate arterial and venous perfusion. The overlap of the two, i.e. arterio-venous overlap or AVOL, preferentially occurs in brain tumors and predicts response to anti-angiogenic therapy. The effects of contrast agent leakage on the AVOL biomarker have yet to be established. DSC was acquired during two separate contrast boluses in ten patients undergoing clinical imaging for brain tumor diagnosis. Three components were modeled with ICA, which included the arterial and venous components. The percentage of each component as well as a third component were determined within contrast enhancing tumor and compared. AVOL within enhancing tumor was also compared between doses. The percentage of enhancing tumor classified as not arterial or venous and instead into a third component with contrast agent leakage apparent in the time-series was significantly greater for the first contrast dose compared to the second. The amount of AVOL detected within enhancing tumor was also significantly greater with the second dose compared to the first. Contrast leakage results in large signal variance classified as a separate component by the ICA algorithm. The use of a second dose mitigates the effect and allows measurement of AVOL within enhancement.

Super enhanced permeability and retention (SUPR) effects in tumors following near infrared photoimmunotherapy

Science.gov (United States)

Kobayashi, Hisataka; Choyke, Peter L.

2016-06-01

To date, the delivery of nano-sized therapeutic agents to cancers largely relies on enhanced permeability and retention (EPR) effects that are caused by the leaky nature of cancer vasculature. However, nano-sized agents delivered in this way have demonstrated limited success in oncology due to the relatively small magnitude of the EPR effect. For achieving superior delivery of nano-sized agents, super-enhanced permeability and retention (SUPR) effects are needed. Near infrared photo-immunotherapy (NIR-PIT) is a recently reported therapy that treats tumors with light therapy and subsequently causes an increase in nano-drug delivery up to 24-fold compared with untreated tumors in which only the EPR effect is present. SUPR effects could enhance delivery into tumor beds of a wide variety of nano-sized agents including particles, antibodies, and protein binding small molecular agents. Therefore, taking advantage of the SUPR effects after NIR-PIT may be a promising avenue to utilize a wide variety of nano-drugs in a highly effective manner.

Applying gold nanoparticles as tumor-vascular disrupting agents during brachytherapy: estimation of endothelial dose enhancement

Energy Technology Data Exchange (ETDEWEB)

Ngwa, Wilfred; Makrigiorgos, G Mike; Berbeco, Ross I, E-mail: mmakrigiorgos@lroc.harvard.ed [Department of Radiation Oncology, Division of Medical Physics and Biophysics, Brigham and Women' s Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115 (United States)

2010-11-07

Tumor vascular disrupting agents (VDAs) represent a promising approach to the treatment of cancer, in view of the tumor vasculature's pivotal role in tumor survival, growth and metastasis. VDAs targeting the tumor's dysmorphic endothelial cells can cause selective and rapid occlusion of the tumor vasculature, leading to tumor cell death from ischemia and extensive hemorrhagic necrosis. In this study, the potential for applying gold nanoparticles (AuNPs) as VDAs, during brachytherapy, is examined. Analytic calculations based on the electron energy loss formula of Cole were carried out to estimate the endothelial dose enhancement caused by radiation-induced photo/Auger electrons originating from AuNPs targeting the tumor endothelium. The endothelial dose enhancement factor (EDEF), representing the ratio of the dose to the endothelium with and without gold nanoparticles was calculated for different AuNP local concentrations, and endothelial cell thicknesses. Four brachytherapy sources were investigated, I-125, Pd-103, Yb-169, as well as 50 kVp x-rays. The results reveal that, even at relatively low intra-vascular AuNP concentrations, ablative dose enhancement to tumor endothelial cells due to photo/Auger electrons from the AuNPs can be achieved. Pd-103 registered the highest EDEF values of 7.4-271.5 for local AuNP concentrations ranging from 7 to 350 mg g{sup -1}, respectively. Over the same concentration range, I-125, 50 kVp and Yb-169 yielded values of 6.4-219.9, 6.3-214.5 and 4.0-99.7, respectively. Calculations of the EDEF as a function of endothelial cell thickness showed that lower energy sources like Pd-103 reach the maximum EDEF at smaller thicknesses. The results also reveal that the highest contribution to the EDEF comes from Auger electrons, apparently due to their shorter range. Overall, the data suggest that ablative dose enhancement to tumor endothelial cells can be achieved by applying tumor vasculature-targeted AuNPs as adjuvants to

Identification of 19 new risk loci and potential regulatory mechanisms influencing susceptibility to testicular germ cell tumor.

Science.gov (United States)

Litchfield, Kevin; Levy, Max; Orlando, Giulia; Loveday, Chey; Law, Philip J; Migliorini, Gabriele; Holroyd, Amy; Broderick, Peter; Karlsson, Robert; Haugen, Trine B; Kristiansen, Wenche; Nsengimana, Jérémie; Fenwick, Kerry; Assiotis, Ioannis; Kote-Jarai, ZSofia; Dunning, Alison M; Muir, Kenneth; Peto, Julian; Eeles, Rosalind; Easton, Douglas F; Dudakia, Darshna; Orr, Nick; Pashayan, Nora; Bishop, D Timothy; Reid, Alison; Huddart, Robert A; Shipley, Janet; Grotmol, Tom; Wiklund, Fredrik; Houlston, Richard S; Turnbull, Clare

2017-07-01

Genome-wide association studies (GWAS) have transformed understanding of susceptibility to testicular germ cell tumors (TGCTs), but much of the heritability remains unexplained. Here we report a new GWAS, a meta-analysis with previous GWAS and a replication series, totaling 7,319 TGCT cases and 23,082 controls. We identify 19 new TGCT risk loci, roughly doubling the number of known TGCT risk loci to 44. By performing in situ Hi-C in TGCT cells, we provide evidence for a network of physical interactions among all 44 TGCT risk SNPs and candidate causal genes. Our findings implicate widespread disruption of developmental transcriptional regulators as a basis of TGCT susceptibility, consistent with failed primordial germ cell differentiation as an initiating step in oncogenesis. Defective microtubule assembly and dysregulation of KIT-MAPK signaling also feature as recurrently disrupted pathways. Our findings support a polygenic model of risk and provide insight into the biological basis of TGCT.

Relationship of preoperative gastric cancer CT enhancement ratio and perfusion parameters with serum tumor marker levels and proliferation molecule expression in tumor lesions

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Yong-Hong Wang

2017-06-01

Full Text Available Objective: To study the relationship of preoperative gastric cancer CT enhancement ratio and perfusion parameters with serum tumor marker levels and proliferation molecule expression in tumor lesions. Methods: A total of 68 patients with gastric cancer treated in the Second Hospital of Yulin City between May 2012 and May 2016 were chosen as observation group and sub-divided into early and middle gastric cancer group (n=41 and advanced gastric cancer group (n=27 according to the tumor stage; 50 patients diagnosed with benign gastric diseases in our hospital during the same period were selected as benign gastric lesion group. CT enhancement rate and perfusion parameters of three groups of patients were detected by CT scan, serum tumor marker levels were evacuated by enzyme-linked immunosorbent assay (ELISA, and the proliferation gene mRNA expression levels were detected by RTPCR method. Results: CER, AF, BV and CL levels of advanced gastric cancer group were higher than those of early and middle gastric cancer group and benign gastric lesion group; serum CA72-4, CA19-9, CA125 and CEA contents of advanced gastric cancer group were higher than those of early and middle gastric cancer group and benign gastric lesion group; CADM1, miRNA-34a and Cystatin M mRNA expression in tissue of advanced gastric cancer group were lower than those of early and middle gastric cancer group and benign gastric lesion group while Survivin and I2PP2A mRNA expression were higher than those of early and middle gastric cancer group and benign gastric lesion group. The Pearson test showed that the CT enhancement rate and perfusion parameters in patients with gastric cancer are directly correlated with the serum tumor marker levels and the proliferation gene expression in tumor lesions. Conclusion: Preoperative gastric cancer CT enhancement rate and perfusion parameters are directly related to the tumor malignancy, and can be used as a reliable method for the long-term tumor

Herpes Simplex Virus Type 2 Enhances HIV-1 Susceptibility by Affecting Langerhans Cell Function

NARCIS (Netherlands)

de Jong, Marein A. W. P.; de Witte, Lot; Taylor, Maureen E.; Geijtenbeek, Teunis B. H.

2010-01-01

Genital herpes is the most prevalent viral sexually transmitted infection worldwide and is mainly caused by HSV type 2 (HSV-2). HSV-2 infection enhances HIV-1 susceptibility, even in the absence of clinical symptoms. In this study, we investigated the effect of HSV-2 on HIV-1 transmission by mucosal

Cordycepin enhances Epstein-Barr virus lytic infection and Epstein-Barr virus-positive tumor treatment efficacy by doxorubicin.

Science.gov (United States)

Du, Yinping; Yu, Jieshi; Du, Li; Tang, Jun; Feng, Wen-Hai

2016-07-01

The consistent latent presence of Epstein-Barr virus (EBV) in tumor cells offers potential for virus-targeted therapies. The switch from the latent form of EBV to the lytic form in tumor cells can lead to tumor cell lysis. In this study, we report that a natural small molecule compound, cordycepin, can induce lytic EBV infection in tumor cells. Subsequently, we demonstrate that cordycepin can enhance EBV reactivating capacity and EBV-positive tumor cell killing ability of low dose doxorubicin. The combination of cordycepin and doxorubicin phosphorylates CCAAT/enhancer binding protein β (C/EBPβ) through protein kinase C (PKC)-p38 mitogen activated protein kinases (p38 MAPK) signaling pathway, and C/EBPβ is required for the activation of lytic EBV infection. Most importantly, an in vivo experiment demonstrates that the combination of cordycepin and doxorubicin is more effective in inhibiting tumor growth in SCID mice than is doxorubicin alone. Our findings establish that cordycepin can enhance the efficacy of conventional chemotherapy for treatment of EBV-positive tumors. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Differential expression of miR-1, a putative tumor suppressing microRNA, in cancer resistant and cancer susceptible mice

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Jessica L. Fleming

2013-04-01

Full Text Available Mus spretus mice are highly resistant to several types of cancer compared to Mus musculus mice. To determine whether differences in microRNA (miRNA expression account for some of the differences in observed skin cancer susceptibility between the strains, we performed miRNA expression profiling of skin RNA for over 300 miRNAs. Five miRNAs, miR-1, miR-124a-3, miR-133a, miR-134, miR-206, were differentially expressed by array and/or qPCR. miR-1 was previously shown to have tumor suppressing abilities in multiple tumor types. We found miR-1 expression to be lower in mouse cutaneous squamous cell carcinomas (cSCCs compared to normal skin. Based on the literature and our expression data, we performed detailed studies on predicted miR-1 targets and evaluated the effect of miR-1 expression on two murine cSCC cell lines, A5 and B9. Following transfection of miR-1, we found decreased mRNA expression of three validated miR-1 targets, Met, Twf1 and Ets1 and one novel target Bag4. Decreased expression of Ets1 was confirmed by Western analysis and by 3’ reporter luciferase assays containing wildtype and mutated Ets1 3’UTR. We evaluated the effect of miR-1 on multiple tumor phenotypes including apoptosis, proliferation, cell cycle and migration. In A5 cells, expression of miR-1 led to decreased proliferation compared to a control miR. miR-1 expression also led to increased apoptosis at later time points (72 and 96 h and to a decrease in cells in S-phase. In summary, we identified five miRNAs with differential expression between cancer resistant and cancer susceptible mice and found that miR-1, a candidate tumor suppressor, has targets with defined roles in tumorigenesis.

FDG-avid portal vein tumor thrombosis from hepatocellular carcinoma in contrast-enhanced FDG PET/CT

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Canh Nguyen

2015-01-01

Full Text Available Objective(s: In this study, we aimed to describe the characteristics of portal vein tumor thrombosis (PVTT, complicating hepatocellular carcinoma (HCC in contrast-enhanced FDG PET/CT scan. Methods: In this retrospective study, 9 HCC patients with FDG-avid PVTT were diagnosed by contrast-enhanced fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT, which is a combination of dynamic liver CT scan, multiphase imaging, and whole-body PET scan. PET and CT DICOM images of patients were imported into the PET/CT imaging system for the re-analysis of contrast enhancement and FDG uptake in thrombus, the diameter of the involved portal vein, and characteristics of liver tumors and metastasis. Results: Two patients with previously untreated HCC and 7 cases with previously treated HCC had FDG-avid PVTT in contrast-enhanced FDG PET/CT scan. During the arterial phase of CT scan, portal vein thrombus showed contrast enhancement in 8 out of 9 patients (88.9%. PET scan showed an increased linear FDG uptake along the thrombosed portal vein in all patients. The mean greatest diameter of thrombosed portal veins was 1.8 ± 0.2 cm, which was significantly greater than that observed in normal portal veins (P<0.001. FDG uptake level in portal vein thrombus was significantly higher than that of blood pool in the reference normal portal vein (P=0.001. PVTT was caused by the direct extension of liver tumors. All patients had visible FDG-avid liver tumors in contrast-enhanced images. Five out of 9 patients (55.6% had no extrahepatic metastasis, 3 cases (33.3% had metastasis of regional lymph nodes, and 1 case (11.1% presented with distant metastasis. The median estimated survival time of patients was 5 months. Conclusion: The intraluminal filling defect consistent with thrombous within the portal vein, expansion of the involved portal vein, contrast enhancement, and linear increased FDG uptake of the thrombus extended from liver tumor are

Tumor-targeted delivery of IL-2 by NKG2D leads to accumulation of antigen-specific CD8+ T cells in the tumor loci and enhanced anti-tumor effects.

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Tae Heung Kang

Full Text Available Interleukin-2 (IL-2 has been shown to promote tumor-specific T-cell proliferation and differentiation but systemic administration of IL-2 results in significant toxicity. Therefore, a strategy that can specifically deliver IL-2 to the tumor location may alleviate concerns of toxicity. Because NKG2D ligands have been shown to be highly expressed in many cancer cells but not in healthy cells, we reason that a chimeric protein consisting of NKG2D linked to IL-2 will lead to the specific targeting of IL-2 to the tumor location. Therefore, we created chimeric proteins consisting of NKG2D linked to Gaussia luciferase (GLuc; a marker protein or IL-2 to form NKG2D-Fc-GLuc and NKG2D-Fc-IL2, respectively. We demonstrated that NKG2D linked to GLuc was able to deliver GLuc to the tumor location in vivo. Furthermore, we showed that TC-1 tumor-bearing mice intramuscularly injected with DNA encoding NKG2D-Fc-IL2, followed by electroporation, exhibited an increased number of luciferase-expressing E7-specific CD8+ T cells at the tumor location. More importantly, treatment with the DNA construct encoding NKG2D-Fc-IL2 significantly enhanced the therapeutic anti-tumor effects generated by intradermal vaccination with therapeutic HPV DNA in tumor-bearing mice. Therefore, by linking NKG2D to IL2, we are able to specifically deliver IL-2 to the tumor location, enhancing antigen-specific T-cell immune response and controlling tumor growth. Our approach represents a platform technology to specifically deliver proteins of interest to tumor loci.

X-ray diffraction enhanced imaging study of intraocular tumors in human beings

International Nuclear Information System (INIS)

Tan Gao; Wang Huaqiao; Chen Yu; Yuan Qing; Li Gang; Zhu Peiping; Zhang Xiaodan; Zhong Xiufeng; Tang Jintian

2010-01-01

Diffraction enhanced imaging (DEI) with edge enhancement is suitable for the observation of weakly absorbing objects. The potential ability of the DEI was explored for displaying the microanatomy and pathology of human eyeball in this work. The images of surgical specimens from malignant intraocular tumor of hospitalized patients were taken using the hard X-rays from the topography station of Beamline 4W1A at Beijing Synchrotron Radiation Facility (BSRF). The obtained radiographic images were analyzed in correlation with those of pathology. The results show that the anatomic and pathologic details of intraocular tumors in human beings can be observed clearly by DEI for the first time, with good visualization of the microscopic details of eyeball ring such as sclera, choroid and other details of intraocular organelles. And the best resolution of DEI images reaches up to the magnitude of several tens of μm. The results suggest that it is capable of exhibiting clearly the details of intraocular tumor using DEI method. (authors)

Multitriggered Tumor-Responsive Drug Delivery Vehicles Based on Protein and Polypeptide Coassembly for Enhanced Photodynamic Tumor Ablation.

Science.gov (United States)

Zhang, Ning; Zhao, Fenfang; Zou, Qianli; Li, Yongxin; Ma, Guanghui; Yan, Xuehai

2016-11-01

Tumor-responsive nanocarriers are highly valuable and demanded for smart drug delivery particularly in the field of photodynamic therapy (PDT), where a quick release of photosensitizers in tumors is preferred. Herein, it is demonstrated that protein-based nanospheres, prepared by the electrostatic assembly of proteins and polypeptides with intermolecular disulfide cross-linking and surface polyethylene glycol coupling, can be used as versatile tumor-responsive drug delivery vehicles for effective PDT. These nanospheres are capable of encapsulation of various photosensitizers including Chlorin e6 (Ce6), protoporphyrin IX, and verteporfin. The Chlorin e6-encapsulated nanospheres (Ce6-Ns) are responsive to changes in pH, redox potential, and proteinase concentration, resulting in multitriggered rapid release of Ce6 in an environment mimicking tumor tissues. In vivo fluorescence imaging results indicate that Ce6-Ns selectively accumulate near tumors and the quick release of Ce6 from Ce6-Ns can be triggered by tumors. In tumors the fluorescence of released Ce6 from Ce6-Ns is observed at 0.5 h postinjection, while in normal tissues the fluorescence appeared at 12 h postinjection. Tumor ablation is demonstrated by in vivo PDT using Ce6-Ns and the biocompatibility of Ce6-Ns is evident from the histopathology imaging, confirming the enhanced in vivo PDT efficacy and the biocompatibility of the assembled drug delivery vehicles. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Targeting the ECM to Enhance Drug Delivery in Nf1-Associated Nerve Sheath Tumors

Science.gov (United States)

2016-10-01

development of the principal discipline(s) of the project? • We have learned that the drug PEGPH20, which degrades a component of connective tissue called...AWARD NUMBER: W81XWH-15-1-0114 TITLE: Targeting the ECM to Enhance Drug Delivery in Nf1-Associated Nerve Sheath Tumors PRINCIPAL INVESTIGATOR...14 Sep 2016 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER NF140089 Targeting the ECM to Enhance Drug Delivery in Nf1-Associated Nerve Sheath Tumors 5b

Enhanced tumor cell killing following BNCT with hyperosmotic mannitol-induced blood-brain barrier disruption and intracarotid injection of boronophenylalanine

International Nuclear Information System (INIS)

Hsieh, C.H.; Hwang, J.J.; Chen, F.D.; Liu, R.S.; Liu, H.M.; Hsueh, Y.W.; Kai, J.J.

2006-01-01

The delivery of boronophenylalanine (BPA) by means of intracarotid injection combined with opening the blood-brain barrier (BBB) have been shown significantly enhanced the tumor boron concentration and the survival time of glioma-bearing rats. However, no direct evidence demonstrates whether this treatment protocol can enhance the cell killing of tumor cells or infiltrating tumor cells and the magnitude of enhanced cell killing. The purpose of the present study was to determine if the tumor cell killing of boron neutron capture therapy could be enhanced by hyperosmotic mannitol-induced BBB disruption using BPA-Fr as the capture agent. F98 glioma-bearing rats were injected intravenously or intracarotidly with BPA at doses of 500 mg/kg body weight (b.w.) and with or without mannitol-induced hyperosmotic BBB disruption. The rats were irradiated with an epithermal neutron beam at the reactor of National Tsing-Hua University (THOR). After neutron beam irradiation, the rats were euthanized and the ipsilateral brains containing intracerebral F98 glioma were removed to perform in vivo/in vitro soft agar clonogenic assay. The results demonstrate BNCT with optimizing the delivery of BPA by means of intracarotid injection combined with opening the BBB by infusing a hyperosmotic solution of mannitol significantly enhanced the cell killing of tumor cells and infiltrating tumor cells, the tumor boron concentration and the boron ratio of tumor to normal brain tissues. (author)

Contrast enhancement and morphological findings of hematopoietic regions of bone marrow on MR imaging. Comparative study with spondylitis and vertebral tumors

Energy Technology Data Exchange (ETDEWEB)

Amano, Yasuo; Hayashi, Hiromitsu; Matsuura, Maki; Watari, Jun; Kumazaki, Tatsuo [Nippon Medical School, Tokyo (Japan)

1995-06-01

The enhanced MR findings of hematopoietic regions in aplastic anemia were compared with those of spondylitis, metastatic vertebral tumors and hematologic neoplasms. The enhanced MR images showed hematopoietic regions to homogeneously enhance and occupy the margin of vertebral bodies, while spondylitis and metastatic tumors appeared as round, inhomogeneously enhancing lesions. MR images of leukemia and myelodysplastic syndrome showed homogeneous enhancement at the margins of vertebrae that was difficult to differentiate from hematopoietic regions. Enhanced MR images were useful in detecting the hematopoietic areas in marrow and differentiating them from spondylitis and metastatic tumors, although further experience is needed to distinguish between tumorous hyperplastic regions and benign hematopoietic regions in marrow. (author).

CCDC26, CDKN2BAS, RTEL1 and TERT Polymorphisms in pediatric brain tumor susceptibility.

Science.gov (United States)

Adel Fahmideh, Maral; Lavebratt, Catharina; Schüz, Joachim; Röösli, Martin; Tynes, Tore; Grotzer, Michael A; Johansen, Christoffer; Kuehni, Claudia E; Lannering, Birgitta; Prochazka, Michaela; Schmidt, Lisbeth S; Feychting, Maria

2015-08-01

The role of genetic polymorphisms in pediatric brain tumor (PBT) etiology is poorly understood. We hypothesized that single nucleotide polymorphisms (SNPs) identified in genome-wide association studies (GWAS) on adult glioma would also be associated with PBT risk. The study is based on the Cefalo study, a population-based multicenter case-control study. Saliva DNA from 245 cases and 489 controls, aged 7-19 years at diagnosis/reference date, was extracted and genotyped for 29 SNPs reported by GWAS to be significantly associated with risk of adult glioma. Data were analyzed using unconditional logistic regression. Stratified analyses were performed for two histological subtypes: astrocytoma alone and the other tumor types combined. The results indicated that four SNPs, CDKN2BAS rs4977756 (p = 0.036), rs1412829 (p = 0.037), rs2157719 (p = 0.018) and rs1063192 (p = 0.021), were associated with an increased susceptibility to PBTs, whereas the TERT rs2736100 was associated with a decreased risk (p = 0.018). Moreover, the stratified analyses showed a decreased risk of astrocytoma associated with RTEL1 rs6089953, rs6010620 and rs2297440 (p trend = 0.022, p trend = 0.042, p trend = 0.029, respectively) as well as an increased risk of this subtype associated with RTEL1 rs4809324 (p trend = 0.033). In addition, SNPs rs10464870 and rs891835 in CCDC26 were associated with an increased risk of non-astrocytoma tumor subtypes (p trend = 0.009, p trend = 0.007, respectively). Our findings indicate that SNPs in CDKN2BAS, TERT, RTEL1 and CCDC26 may be associated with the risk of PBTs. Therefore, we suggest that pediatric and adult brain tumors might share common genetic risk factors and similar etiological pathways. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Polyamine deprivation-induced enhanced uptake of methylglyoxal bis(guanylhydrazone) by tumor cells.

Science.gov (United States)

Seppänen, P; Alhonen-Hongisto, L; Jänne, J

1981-05-05

1. Putrescine and spermidine depletion produced by alpha-difluoromethylornithine, an irreversible inhibitor or ornithine decarboxylase (EC 4.1.1.17), resulted in a strikingly enhanced cellular uptake of methylglyoxal bis(guanylhydrazone) in cultured Ehrlich ascites carcinoma cells and human lymphocytic leukemia cells. 2. A prior priming of the cells with difluoromethylornithine followed by a short exposure of the cells to methylglyoxal bis(guanylhydrazone) rapidly established intracellular concentrations of the latter drug approaching 10 mM. 3. The enhanced transport of methylglyoxal bis(guanylhydrazone) into the tumor cells apparently required metabolic energy as the uptake of extracellular drug rapidly ceased and intracellular methylglyoxal bis(guanylhydrazone) was excreted into the medium when the glycolysis of the tumor cells was inhibited by iodoacetate. 4. A sequential treatment of cultured tumor cells with difluoromethylornithine until established polyamine depletion followed by an addition of low concentrations of methylglyoxal bis(guanylhydrazone) produced an antiproliferative action not achieved with either of the drugs alone. 5. A similar treatment schedule, i.e a priming of mice inoculated with Ehrlich ascites cells with difluoromethylornithine for a few days, likewise enhanced the uptake of methylglyoxal bis(guanylhydrazone) by the carcinoma cells, but only marginally increased the drug concentration in the liver and small intestine of the animals.

Cranial nerve assessment in cavernous sinus tumors with contrast-enhanced 3D fast-imaging employing steady-state acquisition MR imaging

Energy Technology Data Exchange (ETDEWEB)

Amemiya, Shiori; Aoki, Shigeki; Ohtomo, Kuni [University of Tokyo, Department of Radiology, Graduate School of Medicine, Bunkyo-ku, Tokyo (Japan)

2009-07-15

The purpose of this study is to apply contrast-enhanced 3D fast-imaging employing steady-state acquisition (3D-FIESTA) imaging to the evaluation of cranial nerves (CN) in patients with cavernous sinus tumors. Contrast-enhanced 3D-FIESTA images were acquired from ten patients with cavernous sinus tumors with a 3-T unit. In all cases, the trigeminal nerve with tumor involvement was easily identified in the cavernous portions. Although oculomotor and abducens nerves were clearly visualized against the tumor area with intense contrast enhancement, they were hardly identifiable within the area lacking contrast enhancement. The trochlear nerve was visualized in part, but not delineated as a linear structure outside of the lesion. Contrast-enhanced 3D-FIESTA can be useful in the assessment of cranial nerves in and around the cavernous sinus with tumor involvement. (orig.)

Cranial nerve assessment in cavernous sinus tumors with contrast-enhanced 3D fast-imaging employing steady-state acquisition MR imaging

International Nuclear Information System (INIS)

Amemiya, Shiori; Aoki, Shigeki; Ohtomo, Kuni

2009-01-01

The purpose of this study is to apply contrast-enhanced 3D fast-imaging employing steady-state acquisition (3D-FIESTA) imaging to the evaluation of cranial nerves (CN) in patients with cavernous sinus tumors. Contrast-enhanced 3D-FIESTA images were acquired from ten patients with cavernous sinus tumors with a 3-T unit. In all cases, the trigeminal nerve with tumor involvement was easily identified in the cavernous portions. Although oculomotor and abducens nerves were clearly visualized against the tumor area with intense contrast enhancement, they were hardly identifiable within the area lacking contrast enhancement. The trochlear nerve was visualized in part, but not delineated as a linear structure outside of the lesion. Contrast-enhanced 3D-FIESTA can be useful in the assessment of cranial nerves in and around the cavernous sinus with tumor involvement. (orig.)

EVIR: chimeric receptors that enhance dendritic cell cross-dressing with tumor antigens.

Science.gov (United States)

Squadrito, Mario Leonardo; Cianciaruso, Chiara; Hansen, Sarah K; De Palma, Michele

2018-03-01

We describe a lentivirus-encoded chimeric receptor, termed extracellular vesicle (EV)-internalizing receptor (EVIR), which enables the selective uptake of cancer-cell-derived EVs by dendritic cells (DCs). The EVIR enhances DC presentation of EV-associated tumor antigens to CD8 + T cells primarily through MHCI recycling and cross-dressing. EVIRs should facilitate exploring the mechanisms and implications of horizontal transfer of tumor antigens to antigen-presenting cells.

Cross-correlation enhanced stability in a tumor cell growth model with immune surveillance driven by cross-correlated noises

International Nuclear Information System (INIS)

Zeng Chunhua; Zhou Xiaofeng; Tao Shufen

2009-01-01

The transient properties of a tumor cell growth model with immune surveillance driven by cross-correlated multiplicative and additive noises are investigated. The explicit expression of extinction rate from the state of a stable tumor to the state of extinction is obtained. Based on the numerical computations, we find the following: (i) the intensity of multiplicative noise D and the intensity of additive noise α enhance the extinction rate for the case of λ ≤ 0 (i.e. λ denotes cross-correlation intensity between two noises), but for the case of λ > 0, a critical noise intensity D or α exists at which the extinction rate is the smallest; D and α at first weaken the extinction rate and then enhance it. (ii) The immune rate β and the cross-correlation intensity λ play opposite roles on the extinction rate, i.e. β enhances the extinction rate of the tumor cell, while λ weakens the extinction rate of the tumor cell. Namely, the immune rate can enhance the extinction of the tumor cell and the cross-correlation between two noises can enhance stability of the cancer state.

Hedgehog signaling in tumor cells facilitates osteoblast-enhanced osteolytic metastases.

Directory of Open Access Journals (Sweden)

Shamik Das

Full Text Available The remodeling process in bone yields numerous cytokines and chemokines that mediate crosstalk between osteoblasts and osteoclasts and also serve to attract and support metastatic tumor cells. The metastatic tumor cells disturb the equilibrium in bone that manifests as skeletal complications. The Hedgehog (Hh pathway plays an important role in skeletogenesis. We hypothesized that the Hh pathway mediates an interaction between tumor cells and osteoblasts and influences osteoblast differentiation in response to tumor cells. We have determined that breast tumor cells have an activated Hh pathway characterized by upregulation of the ligand, IHH and transcription factor GLI1. Breast cancer cells interact with osteoblasts and cause an enhanced differentiation of pre-osteoblasts to osteoblasts that express increased levels of the osteoclastogenesis factors, RANKL and PTHrP. There is sustained expression of osteoclast-promoting factors, RANKL and PTHrP, even after the osteoblast differentiation ceases and apoptosis sets in. Moreover, tumor cells that are deficient in Hh signaling are compromised in their ability to induce osteoblast differentiation and consequently are inefficient in causing osteolysis. The stimulation of osteoblast differentiation sets the stage for osteoclast differentiation and overall promotes osteolysis. Thus, in the process of developing newer therapeutic strategies against breast cancer metastasis to bone it would worthwhile to keep in mind the role of the Hh pathway in osteoblast differentiation in an otherwise predominant osteolytic phenomenon.

Gd-DOTA enhancement of cerebral and spinal tumors on MR imaging

International Nuclear Information System (INIS)

Berry, I.; Manelfe, C.; Chastin, I.; Arrue, P.; Prere, J.

1987-01-01

The use of Gd-DOTA as a contrast agent in MR imaging to improve the diagnosis of cerebral and spinal tumors was assessed in 20 patients, ten with brain tumors and ten with spinal tumors. Imaging was performed with a 0.5-T Magniscan 5000 unit. T1-weighted (spin-echo and gradient-echo) and T2-weighted (spin-echo) images were acquired before and after intravenous injection of Gd-DOTA, 0.1 mmol/kg. On T1-weighted images, Gd-DOTA enhanced sites of presumed disruption of the blood-brain barrier. This made some brain tumors more conspicuous and helped target biopsies, but did not reveal any additional lesions. On the other hand, the use of Gd-DOTA significantly improved the reliability of spinal tumor imaging compared to imaging performed without contrast agent, allowing delineation of abnormalities on T1-weighted images, which frequently contain fewer artifacts than the most sensitive T2-weighted images. Images obtained with Gd-DOTA could be used by the physician to rule out residual tumor after surgery and to assess recurrences. Additional work should be done to discover whether spinal tumor exploration with MR imaging could include solely T1-weighted sequences, performed before and after contrast agent administration, without T2-weighted sequences

Human tumor cell proliferation evaluated using manganese-enhanced MRI.

Directory of Open Access Journals (Sweden)

Rod D Braun

Full Text Available Tumor cell proliferation can depend on calcium entry across the cell membrane. As a first step toward the development of a non-invasive test of the extent of tumor cell proliferation in vivo, we tested the hypothesis that tumor cell uptake of a calcium surrogate, Mn(2+ [measured with manganese-enhanced MRI (MEMRI], is linked to proliferation rate in vitro.Proliferation rates were determined in vitro in three different human tumor cell lines: C918 and OCM-1 human uveal melanomas and PC-3 prostate carcinoma. Cells growing at different average proliferation rates were exposed to 1 mM MnCl(2 for one hour and then thoroughly washed. MEMRI R(1 values (longitudinal relaxation rates, which have a positive linear relationship with Mn(2+ concentration, were then determined from cell pellets. Cell cycle distributions were determined using propidium iodide staining and flow cytometry. All three lines showed Mn(2+-induced increases in R(1 compared to cells not exposed to Mn(2+. C918 and PC-3 cells each showed a significant, positive correlation between MEMRI R(1 values and proliferation rate (p≤0.005, while OCM-1 cells showed no significant correlation. Preliminary, general modeling of these positive relationships suggested that pellet R(1 for the PC-3 cells, but not for the C918 cells, could be adequately described by simply accounting for changes in the distribution of the cell cycle-dependent subpopulations in the pellet.These data clearly demonstrate the tumor-cell dependent nature of the relationship between proliferation and calcium influx, and underscore the usefulness of MEMRI as a non-invasive method for investigating this link. MEMRI is applicable to study tumors in vivo, and the present results raise the possibility of evaluating proliferation parameters of some tumor types in vivo using MEMRI.

Genetic susceptibility to radiations. Which impact on medical practice

International Nuclear Information System (INIS)

Alapetite, C.; Cosset, J. M.; Bourguignon, M. H.; Masse, R.

2000-01-01

Recent progress especially in the field of gene identification and expression have raised more attention on genetic susceptibility to cancer possibly enhanced by radiation. Radiation therapists are mostly concerned by this question since hypersensitive patients may suffer from adverse effects in normal tissues following a standard radiation therapy and normally sensitive patients could benefit from higher doses of radiation for better treatment of their malignant tumors. Although only a small percentage of individuals are hypersensitive to radiation effects, all medical specialists using ionising radiation should be aware of this new progress in medical knowledge. The present paper reviews the main pathologies (diseases, syndromes ...) known or strongly suspected to be associated with a hypersensitivity to ionizing radiation. Then the main tests capable of detecting in advance such pathologies are analyzed and compared. Finally guidelines are provided, especially to the radiation therapists to limit the risk of severe complications (or even deaths) for this specific subset of patients suffering from a genetic disorder with a susceptibility to radiation

Enhancement of anticancer effect of interferon-γ gene transfer against interferon-γ-resistant tumor by depletion of tumor-associated macrophages.

Science.gov (United States)

Kiyota, Tsuyoshi; Takahashi, Yuki; Watcharanurak, Kanitta; Nishikawa, Makiya; Ohara, Saori; Ando, Mitsuru; Watanabe, Yoshihiko; Takakura, Yoshinobu

2014-05-05

Tumor-associated macrophages (TAMs) negatively affect the therapeutic effects of anticancer agents. To examine the role of TAMs in interferon (IFN)-γ gene therapy, we selected two types of solid tumors, which varied in the number of TAMs, and investigated the effects of IFN-γ gene transfer on tumor growth. Many TAMs were detected in the solid tumors of murine adenocarcinoma colon-26 cells, whereas few TAMs were detected in murine melanoma B16-BL6 cells. IFN-γ gene transfer hardly suppressed the growth of colon-26 tumors, whereas it was effective in suppressing the growth of B16-BL6 tumors. The antiproliferative effects of IFN-γ on cultured colon-26 cells were similar to those on cultured B16-BL6 cells. To evaluate the role of TAMs, we injected clodronate liposomes (CLs) modified with poly(ethylene glycol) (PEG) to functionally deplete TAMs in tumor-bearing mice. Repeated injections of PEG-CLs significantly retarded the growth of colon-26 tumors and combination with IFN-γ gene transfer further inhibited the growth. In contrast, PEG-CLs hardly retarded the growth of B16-BL6 tumors. These results clearly indicate that TAM depletion is effective in enhancing the therapeutic effect of IFN-γ in TAM-repleted and IFN-γ-resistant tumors.

Cavitation-enhanced MR-guided focused ultrasound ablation of rabbit tumors in vivo using phase shift nanoemulsions

International Nuclear Information System (INIS)

Kopechek, Jonathan A; Porter, Tyrone M; Park, Eun-Joo; Zhang, Yong-Zhi; Vykhodtseva, Natalia I; McDannold, Nathan J

2014-01-01

Advanced tumors are often inoperable due to their size and proximity to critical vascular structures. High intensity focused ultrasound (HIFU) has been developed to non-invasively thermally ablate inoperable solid tumors. However, the clinical feasibility of HIFU ablation therapy has been limited by the long treatment times (on the order of hours) and high acoustic intensities required. Studies have shown that inertial cavitation can enhance HIFU-mediated heating by generating broadband acoustic emissions that increase tissue absorption and accelerate HIFU-induced heating. Unfortunately, initiating inertial cavitation in tumors requires high intensities and can be unpredictable. To address this need, phase-shift nanoemulsions (PSNE) have been developed. PSNE consist of lipid-coated liquid perfluorocarbon droplets that are less than 200 nm in diameter, thereby allowing passive accumulation in tumors through leaky tumor vasculature. PSNE can be vaporized into microbubbles in tumors in order to nucleate cavitation activity and enhance HIFU-mediated heating. In this study, MR-guided HIFU treatments were performed on intramuscular rabbit VX2 tumors in vivo to assess the effect of vaporized PSNE on acoustic cavitation and HIFU-mediated heating. HIFU pulses were delivered for 30 s using a 1.5 MHz, MR-compatible transducer, and cavitation emissions were recorded with a 650 kHz ring hydrophone while temperature was monitored using MR thermometry. Cavitation emissions were significantly higher (P < 0.05) after PSNE injection and this was well correlated with enhanced HIFU-mediated heating in tumors. The peak temperature rise induced by sonication was significantly higher (P < 0.05) after PSNE injection. For example, the mean per cent change in temperature achieved at 5.2 W of acoustic power was 46 ± 22% with PSNE injection. The results indicate that PSNE nucleates cavitation which correlates with enhanced HIFU-mediated heating in tumors. This suggests that PSNE could

Investigating tumor perfusion by hyperpolarized (13) C MRI with comparison to conventional gadolinium contrast-enhanced MRI and pathology in orthotopic human GBM xenografts

DEFF Research Database (Denmark)

Park, Ilwoo; von Morze, Cornelius; Lupo, Janine M

2016-01-01

glioblastoma (GBM) model for the characterization of tumor perfusion and compared with standard Gd-based dynamic susceptibility contrast (DSC) MRI data and immunohistochemical analysis from resected brains. Distinct HMCP perfusion characteristics were observed within the GBM tumors compared with contralateral...... for tumor that exhibited high levels of hyperpolarized HMCP signal. The results from this study have demonstrated that hyperpolarized HMCP data can be used as an indicator of tumor perfusion in an orthotopic xenograft model for GBM. Magn Reson Med, 2016. © 2016 Wiley Periodicals, Inc....

Targeting MEK5 Enhances Radiosensitivity of Human Prostate Cancer and Impairs Tumor-Associated Angiogenesis

Science.gov (United States)

2016-09-01

analysis of tumor necrosis factor - alpha resistant human breast cancer cells reveals a MEK5/Erk5-mediated epithelial-mesenchymal transition phenotype...AWARD NUMBER: W81XWH-15-1-0296 TITLE: Targeting MEK5 Enhances Radiosensitivity of Human Prostate Cancer and Impairs Tumor - Associated...Cancer and Impairs Tumor -Associated Angiogenesis 5b. GRANT NUMBER W81XWH-15-1-0296 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER

Alterations of the Blood-Brain Barrier and Regional Perfusion in Tumor Development: MRI Insights from a Rat C6 Glioma Model.

Science.gov (United States)

Huhndorf, Monika; Moussavi, Amir; Kramann, Nadine; Will, Olga; Hattermann, Kirsten; Stadelmann, Christine; Jansen, Olav; Boretius, Susann

2016-01-01

Angiogenesis and anti-angiogenetic medications play an important role in progression and therapy of glioblastoma. In this context, in vivo characterization of the blood-brain-barrier and tumor vascularization may be important for individual prognosis and therapy optimization. We analyzed perfusion and capillary permeability of C6-gliomas in rats at different stages of tumor-growth by contrast enhanced MRI and dynamic susceptibility contrast (DSC) MRI at 7 Tesla. The analyses included maps of relative cerebral blood volume (CBV) and signal recovery derived from DSC data over a time period of up to 35 days after tumor cell injections. In all rats tumor progression was accompanied by temporal and spatial changes in CBV and capillary permeability. A leakage of the blood-brain barrier (slow contrast enhancement) was observed as soon as the tumor became detectable on T2-weighted images. Interestingly, areas of strong capillary permeability (fast signal enhancement) were predominantly localized in the center of the tumor. In contrast, the tumor rim was dominated by an increased CBV and showed the highest vessel density compared to the tumor center and the contralateral hemisphere as confirmed by histology. Substantial regional differences in the tumor highlight the importance of parameter maps in contrast or in addition to region-of-interest analyses. The data vividly illustrate how MRI including contrast-enhanced and DSC-MRI may contribute to a better understanding of tumor development.

Tumor Penetrating Theranostic Nanoparticles for Enhancement of Targeted and Image-guided Drug Delivery into Peritoneal Tumors following Intraperitoneal Delivery.

Science.gov (United States)

Gao, Ning; Bozeman, Erica N; Qian, Weiping; Wang, Liya; Chen, Hongyu; Lipowska, Malgorzata; Staley, Charles A; Wang, Y Andrew; Mao, Hui; Yang, Lily

2017-01-01

The major obstacles in intraperitoneal (i.p.) chemotherapy of peritoneal tumors are fast absorption of drugs into the blood circulation, local and systemic toxicities, inadequate drug penetration into large tumors, and drug resistance. Targeted theranostic nanoparticles offer an opportunity to enhance the efficacy of i.p. therapy by increasing intratumoral drug delivery to overcome resistance, mediating image-guided drug delivery, and reducing systemic toxicity. Herein we report that i.p. delivery of urokinase plasminogen activator receptor (uPAR) targeted magnetic iron oxide nanoparticles (IONPs) led to intratumoral accumulation of 17% of total injected nanoparticles in an orthotopic mouse pancreatic cancer model, which was three-fold higher compared with intravenous delivery. Targeted delivery of near infrared dye labeled IONPs into orthotopic tumors could be detected by non-invasive optical and magnetic resonance imaging. Histological analysis revealed that a high level of uPAR targeted, PEGylated IONPs efficiently penetrated into both the peripheral and central tumor areas in the primary tumor as well as peritoneal metastatic tumor. Improved theranostic IONP delivery into the tumor center was not mediated by nonspecific macrophage uptake and was independent from tumor blood vessel locations. Importantly, i.p. delivery of uPAR targeted theranostic IONPs carrying chemotherapeutics, cisplatin or doxorubicin, significantly inhibited the growth of pancreatic tumors without apparent systemic toxicity. The levels of proliferating tumor cells and tumor vessels in tumors treated with the above theranostic IONPs were also markedly decreased. The detection of strong optical signals in residual tumors following i.p. therapy suggested the feasibility of image-guided surgery to remove drug-resistant tumors. Therefore, our results support the translational development of i.p. delivery of uPAR-targeted theranostic IONPs for image-guided treatment of peritoneal tumors.

Multi-Parametric MRI and Texture Analysis to Visualize Spatial Histologic Heterogeneity and Tumor Extent in Glioblastoma.

Directory of Open Access Journals (Sweden)

Leland S Hu

Full Text Available Genetic profiling represents the future of neuro-oncology but suffers from inadequate biopsies in heterogeneous tumors like Glioblastoma (GBM. Contrast-enhanced MRI (CE-MRI targets enhancing core (ENH but yields adequate tumor in only ~60% of cases. Further, CE-MRI poorly localizes infiltrative tumor within surrounding non-enhancing parenchyma, or brain-around-tumor (BAT, despite the importance of characterizing this tumor segment, which universally recurs. In this study, we use multiple texture analysis and machine learning (ML algorithms to analyze multi-parametric MRI, and produce new images indicating tumor-rich targets in GBM.We recruited primary GBM patients undergoing image-guided biopsies and acquired pre-operative MRI: CE-MRI, Dynamic-Susceptibility-weighted-Contrast-enhanced-MRI, and Diffusion Tensor Imaging. Following image coregistration and region of interest placement at biopsy locations, we compared MRI metrics and regional texture with histologic diagnoses of high- vs low-tumor content (≥80% vs <80% tumor nuclei for corresponding samples. In a training set, we used three texture analysis algorithms and three ML methods to identify MRI-texture features that optimized model accuracy to distinguish tumor content. We confirmed model accuracy in a separate validation set.We collected 82 biopsies from 18 GBMs throughout ENH and BAT. The MRI-based model achieved 85% cross-validated accuracy to diagnose high- vs low-tumor in the training set (60 biopsies, 11 patients. The model achieved 81.8% accuracy in the validation set (22 biopsies, 7 patients.Multi-parametric MRI and texture analysis can help characterize and visualize GBM's spatial histologic heterogeneity to identify regional tumor-rich biopsy targets.

Ultrasound sonication with microbubbles disrupts blood vessels and enhances tumor treatments of anticancer nanodrug

Directory of Open Access Journals (Sweden)

Lin CY

2012-04-01

Full Text Available Chung-Yin Lin1*, Hsiao-Ching Tseng1*, Heng-Ruei Shiu1, Ming-Fang Wu2, Cheng-Ying Chou3, Win-Li Lin1,41Institute of Biomedical Engineering, 2Laboratory Animal Center, 3Department of Bio-Industrial Mechatronics Engineering, National Taiwan University, Taipei, Taiwan; 4Division of Medical Engineering Research, National Health Research Institutes, Miaoli, Taiwan*These authors contributed equally to this workAbstract: Ultrasound (US sonication with microbubbles (MBs has the potential to disrupt blood vessels and enhance the delivery of drugs into the sonicated tissues. In this study, mouse ear tumors were employed to investigate the therapeutic effects of US, MBs, and pegylated liposomal doxorubicin (PLD on tumors. Tumors started to receive treatments when they grew up to about 15 mm3 (early stage with injection of PLD 10 mg/kg, or up to 50 mm3 (medium stage with PLD 6 (or 4 mg/kg. Experiments included the control, PLD alone, PLD + MBs + US, US alone, and MBs + US groups. The procedure for the PLD + MBs + US group was that PLD was injected first, MB (SonoVue injection followed, and then US was immediately sonicated on the tumor. The results showed that: (1 US sonication with MBs was always able to produce a further hindrance to tumor growth for both early and medium-stage tumors; (2 for the medium-stage tumors, 6 mg/kg PLD alone was able to inhibit their growth, while it did not work for 4 mg/kg PLD alone; (3 with the application of MBs + US, 4 mg/kg PLD was able to inhibit the growth of medium-stage tumors; (4 for early stage tumors after the first treatment with a high dose of PLD alone (10 mg/kg, the tumor size still increased for several days and then decreased (a biphasic pattern; (5 MBs + US alone was able to hinder the growth of early stage tumors, but unable to hinder that of medium stage tumors. The results of histological examinations and blood perfusion measurements indicated that the application of MBs + US disrupts the tumor blood

TU-F-CAMPUS-T-03: Enhancing the Tumor Specific Radiosensitization Using Molecular Targeted Gold Nanorods

International Nuclear Information System (INIS)

Diagaradjane, P; Deorukhkar, A; Sankaranarayanapillai, M; Singh, P; Manohar, N; Tailor, R; Cho, S; Goodrich, G; Krishnan, S

2015-01-01

Purpose: Gold nanoparticle (GNP) mediated radiosensitization has gained significant attention in recent years. However, the widely used passive targeting strategy requires high concentration of GNPs to induce the desired therapeutic effect, thus dampening the enthusiasm for clinical translation. The purpose of this study is to utilize a molecular targeting strategy to minimize the concentration of GNPs injected while simultaneously enhancing the tumor specific radiosensitization for an improved therapeutic outcome. Methods: Cetuximab (antibody specific to the epidermal growth factor receptor that is over-expressed in tumors) conjugated gold nanorods (cGNRs) was used for the tumor targeting. The binding affinity, internalization, and in vitro radiosensitization were evaluated using dark field microscopy, transmission electron microscopy, and clonogenic cell survival assay, respectively. In vivo biodistribution in tumor (HCT116-colorectal cancer cells) bearing mice were quantified using inductively coupled plasma mass spectrometry. In vivo radiosensitization potential was tested using 250-kVp x-rays and clinically relevant 6-MV radiation beams. Results: cGNRs displayed excellent cell-surface binding and internalization (∼31,000 vs 12,000/cell) when compared to unconjugated GNRs (pGNRs). In vitro, the dose enhancement factor at 10% survival (DEF10) was estimated as 1.06 and 1.17, respectively for both 250-kVp and 6-MV beams. In vivo biodistribution analysis revealed enhanced uptake of cGNRs in tumor (1.3 µg/g of tumor tissue), which is ∼1000-fold less than the reported values using passive targeting strategy. Nonetheless, significant radiosensitization was observed in vivo with cGNRs when compared to pGNRs, when irradiated with 250-kVp (tumor volume doubling time 35 days vs 25 days; p=0.002) and 6 MV (17 days vs 13 days; p=0.0052) beams. Conclusion: The enhanced radiosensitization effect observed with very low intratumoral concentrations of gold and megavoltage x

TU-F-CAMPUS-T-03: Enhancing the Tumor Specific Radiosensitization Using Molecular Targeted Gold Nanorods

Energy Technology Data Exchange (ETDEWEB)

Diagaradjane, P [M.D. Anderson Cancer Center, Houston, TX (United States); Deorukhkar, A; Sankaranarayanapillai, M; Singh, P [The UT MD Anderson Cancer Center, Houston, TX (United States); Manohar, N; Tailor, R; Cho, S [UT MD Anderson Cancer Center, Houston, TX (United States); Goodrich, G [Nanospectra Biosciences Inc, Houston, TX (United States); Krishnan, S [The University of Texas MD Anderson Cancer Center, Houston, TX (United States)

2015-06-15

Purpose: Gold nanoparticle (GNP) mediated radiosensitization has gained significant attention in recent years. However, the widely used passive targeting strategy requires high concentration of GNPs to induce the desired therapeutic effect, thus dampening the enthusiasm for clinical translation. The purpose of this study is to utilize a molecular targeting strategy to minimize the concentration of GNPs injected while simultaneously enhancing the tumor specific radiosensitization for an improved therapeutic outcome. Methods: Cetuximab (antibody specific to the epidermal growth factor receptor that is over-expressed in tumors) conjugated gold nanorods (cGNRs) was used for the tumor targeting. The binding affinity, internalization, and in vitro radiosensitization were evaluated using dark field microscopy, transmission electron microscopy, and clonogenic cell survival assay, respectively. In vivo biodistribution in tumor (HCT116-colorectal cancer cells) bearing mice were quantified using inductively coupled plasma mass spectrometry. In vivo radiosensitization potential was tested using 250-kVp x-rays and clinically relevant 6-MV radiation beams. Results: cGNRs displayed excellent cell-surface binding and internalization (∼31,000 vs 12,000/cell) when compared to unconjugated GNRs (pGNRs). In vitro, the dose enhancement factor at 10% survival (DEF10) was estimated as 1.06 and 1.17, respectively for both 250-kVp and 6-MV beams. In vivo biodistribution analysis revealed enhanced uptake of cGNRs in tumor (1.3 µg/g of tumor tissue), which is ∼1000-fold less than the reported values using passive targeting strategy. Nonetheless, significant radiosensitization was observed in vivo with cGNRs when compared to pGNRs, when irradiated with 250-kVp (tumor volume doubling time 35 days vs 25 days; p=0.002) and 6 MV (17 days vs 13 days; p=0.0052) beams. Conclusion: The enhanced radiosensitization effect observed with very low intratumoral concentrations of gold and megavoltage x

Enhanced tumor responses through therapies combining CCNU, MISO and radiation

International Nuclear Information System (INIS)

Siemann, D.W.; Hill, S.A.

1984-01-01

Studies were performed to determine whether the radiation sensitizer misonidazole (MISO) could enhance the tumor control probability in a treatment strategy combining radiation and the nitrosourea 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU). In initial experiments KHT sarcoma-bearing mice were injected with 1.0 mg/g of MISO simultaneously with a 20 mg/kg dose of CCNU 30-40 min prior to irradiation (1500 rad). With this treatment protocol approximately 60% of the mice were found to be tumor-free 100 days post treatment. By comparison all 2 agent combinations led to 0% cures. To evaluate the relative importance of chemopotentiation versus radiosensitization in the 3 agent protocol, tumors were treated with MISO plus one anti-tumor agent (either radiation of CCNU) and then at times ranging from 0 to 24 hr later exposed to the other agent. When the time between treatments was 0 to 6 hr, a 60 to 80% tumor control rate was achieved for both MISO plus radiation followed by CCNU and MISO plus CCNU followed by radiation. However if the time interval was increased to 18 or 24 hr, the cure rate in the former treatment regimen dropped to 10% while that of the latter remained high at 40%. The data therefore indicate that (1) improved tumor responses may be achieved when MISO is added to a radiation-chemotherapy combination and (2) MISO may be more effective in such a protocol when utilized as a chemopotentiator

Contrast-enhanced helical CT of the pancreas. Optimal timing of imaging for pancreatic tumor evaluation

International Nuclear Information System (INIS)

Koide, Kazuki; Sekiguchi, Ryuzo

2001-01-01

We performed three-phase helical CT in patients suspected pancreatic tumors and investigated the optimal timing of imaging for evaluation of the pancreatic mass. The pancreatic-phase was superior in detecting pancreatic tumors, including islet cell tumors that may show strong enhancement. However, portal vein-phase imaging was also superior in 16.7% of our patients. Taking into account examination for hepatic metastasis, helical CT of any pancreatic tumor should include images obtained in the pancreatic and portal vein phases. (author)

Differentiation of grade II/III and grade IV glioma by combining ''T1 contrast-enhanced brain perfusion imaging'' and susceptibility-weighted quantitative imaging

International Nuclear Information System (INIS)

Saini, Jitender; Gupta, Pradeep Kumar; Gupta, Rakesh Kumar; Sahoo, Prativa; Singh, Anup; Patir, Rana; Ahlawat, Suneeta; Beniwal, Manish; Thennarasu, K.; Santosh, Vani

2018-01-01

MRI is a useful method for discriminating low- and high-grade glioma using perfusion MRI and susceptibility-weighted imaging (SWI). The purpose of this study is to evaluate the usefulness of T1-perfusion MRI and SWI in discriminating among grade II, III, and IV gliomas. T1-perfusion MRI was used to measure relative cerebral blood volume (rCBV) in 129 patients with glioma (70 grade IV, 33 grade III, and 26 grade II tumors). SWI was also used to measure the intratumoral susceptibility signal intensity (ITSS) scores for each tumor in these patients. rCBV and ITSS values were compared to seek differences between grade II vs. grade III, grade III vs. grade IV, and grade III+II vs. grade IV tumors. Significant differences in rCBV values of the three grades of the tumors were noted and pairwise comparisons showed significantly higher rCBV values in grade IV tumors as compared to grade III tumors, and similarly increased rCBV was seen in the grade III tumors as compared to grade II tumors (p < 0.001). Grade IV gliomas showed significantly higher ITSS scores on SWI as compared to grade III tumors (p < 0.001) whereas insignificant difference was seen on comparing ITSS scores of grade III with grade II tumors. Combining the rCBV and ITSS resulted in significant improvement in the discrimination of grade III from grade IV tumors. The combination of rCBV values derived from T1-perfusion MRI and SWI derived ITSS scores improves the diagnostic accuracy for discrimination of grade III from grade IV gliomas. (orig.)

Differentiation of grade II/III and grade IV glioma by combining ''T1 contrast-enhanced brain perfusion imaging'' and susceptibility-weighted quantitative imaging

Energy Technology Data Exchange (ETDEWEB)

Saini, Jitender [National Institute of Mental Health and Neurosciences, Neuroimaging and Interventional Radiology, Bangalore (India); Gupta, Pradeep Kumar; Gupta, Rakesh Kumar [Fortis Memorial Research Institute, Department of Radiology and Imaging, Gurugram (India); Sahoo, Prativa [Philips Health System, Philips India Limited, Bangalore (India); Beckman Research Institute, Mathematical Oncology, Duarte, CA (United States); Singh, Anup [Indian Institute of Technology Delhi, Center for Biomedical Engineering, Delhi (India); Patir, Rana [Fortis Memorial Research Institute, Department of Neurosurgery, Gurugram (India); Ahlawat, Suneeta [Fortis Memorial Research Institute, SRL Diagnostics, Gurugram (India); Beniwal, Manish [National Institute of Mental Health and Neurosciences, Department of Neurosurgery, Bangalore (India); Thennarasu, K. [National Institute of Mental Health and Neurosciences, Department of Biostatistics, Bangalore (India); Santosh, Vani [National Institute of Mental Health and Neurosciences, Department of Neuropathology, Bangalore (India)

2018-01-15

MRI is a useful method for discriminating low- and high-grade glioma using perfusion MRI and susceptibility-weighted imaging (SWI). The purpose of this study is to evaluate the usefulness of T1-perfusion MRI and SWI in discriminating among grade II, III, and IV gliomas. T1-perfusion MRI was used to measure relative cerebral blood volume (rCBV) in 129 patients with glioma (70 grade IV, 33 grade III, and 26 grade II tumors). SWI was also used to measure the intratumoral susceptibility signal intensity (ITSS) scores for each tumor in these patients. rCBV and ITSS values were compared to seek differences between grade II vs. grade III, grade III vs. grade IV, and grade III+II vs. grade IV tumors. Significant differences in rCBV values of the three grades of the tumors were noted and pairwise comparisons showed significantly higher rCBV values in grade IV tumors as compared to grade III tumors, and similarly increased rCBV was seen in the grade III tumors as compared to grade II tumors (p < 0.001). Grade IV gliomas showed significantly higher ITSS scores on SWI as compared to grade III tumors (p < 0.001) whereas insignificant difference was seen on comparing ITSS scores of grade III with grade II tumors. Combining the rCBV and ITSS resulted in significant improvement in the discrimination of grade III from grade IV tumors. The combination of rCBV values derived from T1-perfusion MRI and SWI derived ITSS scores improves the diagnostic accuracy for discrimination of grade III from grade IV gliomas. (orig.)

Supercritical-Carbon Dioxide Fluid Extract from Chrysanthemum indicum Enhances Anti-Tumor Effect and Reduces Toxicity of Bleomycin in Tumor-Bearing Mice

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Hong-Mei Yang

2017-02-01

Full Text Available Bleomycin (BLM, a family of anti-tumor drugs, was reported to exhibit severe side effects limiting its usage in clinical treatment. Therefore, finding adjuvants that enhance the anti-tumor effect and reduce the detrimental effect of BLM is a prerequisite. Chrysanthemum indicum, an edible flower, possesses abundant bioactivities; the supercritical-carbon dioxide fluid extract from flowers and buds of C. indicum (CISCFE have strong anti-inflammatory, anti-oxidant, and lung protective effects. However, the role of CISCFE combined with BLM treatment on tumor-bearing mice remains unclear. The present study aimed to investigate the potential synergistic effect and the underlying mechanism of CISCFE combined with BLM in the treatment of hepatoma 22 (H22 tumor-bearing mice. The results suggested that the oral administration of CISCFE combined with BLM could markedly prolong the life span, attenuate the BLM-induced pulmonary fibrosis, suppress the production of pro-inflammatory cytokines (interleukin-6, tumor necrosis factor-α, activities of myeloperoxidase, and malondiadehyde. Moreover, CISCFE combined with BLM promoted the ascites cell apoptosis, the activities of caspases 3 and 8, and up-regulated the protein expression of p53 and down-regulated the transforming growth factor-β1 by activating the gene expression of miR-29b. Taken together, these results indicated that CISCFE could enhance the anti-cancer activity of BLM and reduce the BLM-induced pulmonary injury in H22 tumor-bearing mice, rendering it as a potential adjuvant drug with chemotherapy after further investigation in the future.

The Role of Hydrogen-Enhanced Strain-Induced Lattice Defects on Hydrogen Embrittlement Susceptibility of X80 Pipeline Steel

Science.gov (United States)

Hattori, M.; Suzuki, H.; Seko, Y.; Takai, K.

2017-08-01

Studies to date have not completely determined the factors influencing hydrogen embrittlement of ferrite/bainite X80 pipeline steel. Hydrogen embrittlement susceptibility was evaluated based on fracture strain in tensile testing. We conducted a thermal desorption analysis to measure the amount of tracer hydrogen corresponding to that of lattice defects. Hydrogen embrittlement susceptibility and the amount of tracer hydrogen significantly increased with decreasing crosshead speed. Additionally, a significant increase in the formation of hydrogen-enhanced strain-induced lattice defects was observed immediately before the final fracture. In contrast to hydrogen-free specimens, the fracture surface of the hydrogen-charged specimens exhibited shallower dimples without nuclei, such as secondary phase particles. These findings indicate that the presence of hydrogen enhanced the formation of lattice defects, particularly just prior to the occurrence of final fracture. This in turn enhanced the formation of shallower dimples, thereby potentially causing premature fracture of X80 pipeline steel at lower crosshead speeds.

Microarray Gene Expression Analysis of Murine Tumor Heterogeneity Defined by Dynamic Contrast-Enhanced MRI

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Nick G. Costouros

2002-07-01

Full Text Available Current methods of studying angiogenesis are limited in their ability to serially evaluate in vivo function throughout a target tissue. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI and pharmacokinetic modeling provide a useful method for evaluating tissue vasculature based on contrast accumulation and washout. While it is often assumed that areas of high contrast enhancement and washout comprise areas of increased angiogenesis and tumor activity, the actual molecular pathways that are active in such areas are poorly understood. Using DCE-MRI in a murine subcutaneous tumor model, we were able to perform pharmacokinetic functional analysis of a tumor, coregistration of MRI images with histological cross-sections, immunohistochemistry, laser capture microdissection, and genetic profiling of tumor heterogeneity based on pharmacokinetic parameters. Using imaging as a template for biologic investigation, we have not found evidence of increased expression of proangiogenic modulators at the transcriptional level in either distinct pharmacokinetic region. Furthermore, these regions show no difference on histology and CD31 immunohistochemistry. However, the expression of ribosomal proteins was greatly increased in high enhancement and washout regions, implying increased protein translation and consequent increased cellular activity. Together, these findings point to the potential importance of posttranscriptional regulation in angiogenesis and the need for the development of angiogenesis-specific contrast agents to evaluate in vivo angiogenesis at a molecular level.

Cavitation-enhanced MR-guided focused ultrasound ablation of rabbit tumors in vivo using phase shift nanoemulsions

Science.gov (United States)

Kopechek, Jonathan A.; Park, Eun-Joo; Zhang, Yong-Zhi; Vykhodtseva, Natalia I.; McDannold, Nathan J.; Porter, Tyrone M.

2014-07-01

Advanced tumors are often inoperable due to their size and proximity to critical vascular structures. High intensity focused ultrasound (HIFU) has been developed to non-invasively thermally ablate inoperable solid tumors. However, the clinical feasibility of HIFU ablation therapy has been limited by the long treatment times (on the order of hours) and high acoustic intensities required. Studies have shown that inertial cavitation can enhance HIFU-mediated heating by generating broadband acoustic emissions that increase tissue absorption and accelerate HIFU-induced heating. Unfortunately, initiating inertial cavitation in tumors requires high intensities and can be unpredictable. To address this need, phase-shift nanoemulsions (PSNE) have been developed. PSNE consist of lipid-coated liquid perfluorocarbon droplets that are less than 200 nm in diameter, thereby allowing passive accumulation in tumors through leaky tumor vasculature. PSNE can be vaporized into microbubbles in tumors in order to nucleate cavitation activity and enhance HIFU-mediated heating. In this study, MR-guided HIFU treatments were performed on intramuscular rabbit VX2 tumors in vivo to assess the effect of vaporized PSNE on acoustic cavitation and HIFU-mediated heating. HIFU pulses were delivered for 30 s using a 1.5 MHz, MR-compatible transducer, and cavitation emissions were recorded with a 650 kHz ring hydrophone while temperature was monitored using MR thermometry. Cavitation emissions were significantly higher (P cavitation which correlates with enhanced HIFU-mediated heating in tumors. This suggests that PSNE could potentially be used to reduce the time and/or acoustic intensity required for HIFU-mediated heating, thereby increasing the feasibility and clinical efficacy of HIFU thermal ablation therapy.

Natural Compounds Regulate Glycolysis in Hypoxic Tumor Microenvironment

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Jian-Li Gao

2015-01-01

Full Text Available In the early twentieth century, Otto Heinrich Warburg described an elevated rate of glycolysis occurring in cancer cells, even in the presence of atmospheric oxygen (the Warburg effect. Recently it became a therapeutically interesting strategy and is considered as an emerging hallmark of cancer. Hypoxia inducible factor-1 (HIF-1 is one of the key transcription factors that play major roles in tumor glycolysis and could directly trigger Warburg effect. Thus, how to inhibit HIF-1-depended Warburg effect to assist the cancer therapy is becoming a hot issue in cancer research. In fact, HIF-1 upregulates the glucose transporters (GLUT and induces the expression of glycolytic enzymes, such as hexokinase, pyruvate kinase, and lactate dehydrogenase. So small molecules of natural origin used as GLUT, hexokinase, or pyruvate kinase isoform M2 inhibitors could represent a major challenge in the field of cancer treatment. These compounds aim to suppress tumor hypoxia induced glycolysis process to suppress the cell energy metabolism or enhance the susceptibility of tumor cells to radio- and chemotherapy. In this review, we highlight the role of natural compounds in regulating tumor glycolysis, with a main focus on the glycolysis under hypoxic tumor microenvironment.

Negative mood state enhances the susceptibility to unpleasant events: neural correlates from a music-primed emotion classification task.

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Jiajin Yuan

Full Text Available BACKGROUND: Various affective disorders are linked with enhanced processing of unpleasant stimuli. However, this link is likely a result of the dominant negative mood derived from the disorder, rather than a result of the disorder itself. Additionally, little is currently known about the influence of mood on the susceptibility to emotional events in healthy populations. METHOD: Event-Related Potentials (ERP were recorded for pleasant, neutral and unpleasant pictures while subjects performed an emotional/neutral picture classification task during positive, neutral, or negative mood induced by instrumental Chinese music. RESULTS: Late Positive Potential (LPP amplitudes were positively related to the affective arousal of pictures. The emotional responding to unpleasant pictures, indicated by the unpleasant-neutral differences in LPPs, was enhanced during negative compared to neutral and positive moods in the entire LPP time window (600-1000 ms. The magnitude of this enhancement was larger with increasing self-reported negative mood. In contrast, this responding was reduced during positive compared to neutral mood in the 800-1000 ms interval. Additionally, LPP reactions to pleasant stimuli were similar across positive, neutral and negative moods except those in the 800-900 ms interval. IMPLICATIONS: Negative mood intensifies the humans' susceptibility to unpleasant events in healthy individuals. In contrast, music-induced happy mood is effective in reducing the susceptibility to these events. Practical implications of these findings were discussed.

Inherited susceptibility to cancer and other factors influencing occurrence of cancer

International Nuclear Information System (INIS)

Pawlak, A.L.

1994-01-01

The types of defects and polymorphisms leading to hereditary susceptibility to cancer include proneness to increased DNA damage, recessive syndromes of faulty DNA repair and differentiation, as well as dominant mutations of cell cycle and control proliferation. The cancer susceptibility syndromes inherited in a dominant fashion are caused by mutations in tumor suppressor genes. These genes are recessive in relation to wild type alleles. In two syndromes of hereditary mutations in tumor suppressor genes (Rb and WT2), their expression 'in vivo' may be influenced by the sex of the transmitting parent, what points to modulation by imprinting. Genetic heterogeneity of the population in susceptibility to genotoxic agents is related to the individual variation in acceptable levels of exposure to agents and factors, such as products of incomplete combustion (PIC), UV ('xeroderma pigmentosum') and ionizing radiation ('ataxia telangiectasia'). DNA damage and adducts are considered to be indicative of genotoxic exposure and its effect as well as modulation of carcinogenic damage by genetic polymorphisms. Gene and protein polymorphisms are considered as markers of increased individual risk. Since environmental factors are considered to be able to control, the individual susceptibility to enhanced DNA damage and environmentally induced cancers could be counteracted by decreasing the levels of contamination or exposure. This explains the wide interest in markers of this individual sensitivity. Most of the postulated markers of sensitivity to PIV do not, however, prove to be generally applicable in that sense. Their prognostic value is limited either by low amplitude of the effect, or by their character specific either to the population or to the cancer type. The polymorphisms most relevant to cancers induced by PIC exposures may be those of inductibility of benzopyrene hydroxylase, and some other DNA polymorphisms concerning the CYP1A1 gene. (author). 24 refs, 1 fig., 3 tabs

Tumor-infiltrating lymphocyte activity is enhanced in tumors with low IL-10 production in HBV-induced hepatocellular carcinoma

International Nuclear Information System (INIS)

Shi, Yang; Song, Qingwei; Hu, Dianhe; Zhuang, Xiaohu; Yu, Shengcai

2015-01-01

Hepatocellular carcinoma (HCC) is one of the most common cancers and can be induced by chronic HBV infection. The role of HBV-specific immune responses in mediating tumorigenesis and HCC prognosis is debated. The effect of intratumoral microenvironment on tumor-infiltrating lymphocytes (TILs) is also unclear. Here, we examined resected tumor tissue from 36 patients with HBV-induced HCC. We categorized study cohort based on ex vivo IL-10 secretion by tumor cells into high IL-10-secreting (Hi10) and low IL-10-secreting (Lo10) groups, and found that the Lo10 group was less sensitive to TLR ligand stimulation. TILs from the Lo10 group contained higher frequencies of HBV-specific IFN-g-producing cells and total IFN-g-producing cells, and possessed higher proliferative capacity. Moreover, the proliferative capacity of TILs from the Hi10 group was negatively correlated with IL-10 secretion from tumor cells. Together, our data demonstrated that low IL-10-producing capacity in HBV-induced HCC tumors is associated with enhanced TIL activity. - Highlights: • We examined intratumoral IL-10 production in HBV-induced HCC. • We grouped HCC tumors into Hi10 and Lo10 groups based on their IL-10 production. • Lo10 groups had better IFN-g response by TILs. • Lo10 groups had better TIL proliferative capacity. • Lo10 group tumor cells were refractory to TLR ligand stimulation

Tumor-infiltrating lymphocyte activity is enhanced in tumors with low IL-10 production in HBV-induced hepatocellular carcinoma

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Shi, Yang, E-mail: yangshi_xz@126.com; Song, Qingwei; Hu, Dianhe; Zhuang, Xiaohu; Yu, Shengcai

2015-05-22

Hepatocellular carcinoma (HCC) is one of the most common cancers and can be induced by chronic HBV infection. The role of HBV-specific immune responses in mediating tumorigenesis and HCC prognosis is debated. The effect of intratumoral microenvironment on tumor-infiltrating lymphocytes (TILs) is also unclear. Here, we examined resected tumor tissue from 36 patients with HBV-induced HCC. We categorized study cohort based on ex vivo IL-10 secretion by tumor cells into high IL-10-secreting (Hi10) and low IL-10-secreting (Lo10) groups, and found that the Lo10 group was less sensitive to TLR ligand stimulation. TILs from the Lo10 group contained higher frequencies of HBV-specific IFN-g-producing cells and total IFN-g-producing cells, and possessed higher proliferative capacity. Moreover, the proliferative capacity of TILs from the Hi10 group was negatively correlated with IL-10 secretion from tumor cells. Together, our data demonstrated that low IL-10-producing capacity in HBV-induced HCC tumors is associated with enhanced TIL activity. - Highlights: • We examined intratumoral IL-10 production in HBV-induced HCC. • We grouped HCC tumors into Hi10 and Lo10 groups based on their IL-10 production. • Lo10 groups had better IFN-g response by TILs. • Lo10 groups had better TIL proliferative capacity. • Lo10 group tumor cells were refractory to TLR ligand stimulation.

Diagnostic examination performance by using microvascular leakage, cerebral blood volume, and blood flow derived from 3-T dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging in the differentiation of glioblastoma multiforme and brain metastasis

International Nuclear Information System (INIS)

Server, Andres; Nakstad, Per H.; Orheim, Tone E.D.; Graff, Bjoern A.; Josefsen, Roger; Kumar, Theresa

2011-01-01

Conventional magnetic resonance (MR) imaging has limited capacity to differentiate between glioblastoma multiforme (GBM) and metastasis. The purposes of this study were: (1) to compare microvascular leakage (MVL), cerebral blood volume (CBV), and blood flow (CBF) in the distinction of metastasis from GBM using dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging (DSC-MRI), and (2) to estimate the diagnostic accuracy of perfusion and permeability MR imaging. A prospective study of 61 patients (40 GBMs and 21 metastases) was performed at 3 T using DSC-MRI. Normalized rCBV and rCBF from tumoral (rCBVt, rCBFt), peri-enhancing region (rCBVe, rCBFe), and by dividing the value in the tumor by the value in the peri-enhancing region (rCBVt/e, rCBFt/e), as well as MVL were calculated. Hemodynamic and histopathologic variables were analyzed statistically and Spearman/Pearson correlations. Receiver operating characteristic curve analysis was performed for each of the variables. The rCBVe, rCBFe, and MVL were significantly greater in GBMs compared with those of metastases. The optimal cutoff value for differentiating GBM from metastasis was 0.80 which implies a sensitivity of 95%, a specificity of 92%, a positive predictive value of 86%, and a negative predictive value of 97% for rCBVe ratio. We found a modest correlation between rCBVt and rCBFt ratios. MVL measurements in GBMs are significantly higher than those in metastases. Statistically, both rCBVe, rCBVt/e and rCBFe, rCBFt/e were useful in differentiating between GBMs and metastases, supporting the hypothesis that perfusion MR imaging can detect infiltration of tumor cells in the peri-enhancing region. (orig.)

Diagnostic examination performance by using microvascular leakage, cerebral blood volume, and blood flow derived from 3-T dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging in the differentiation of glioblastoma multiforme and brain metastasis

Energy Technology Data Exchange (ETDEWEB)

Server, Andres; Nakstad, Per H. [Oslo University Hospital-Ullevaal, Section of Neuroradiology, Department of Radiology and Nuclear Medicine, Oslo (Norway); University of Oslo, Oslo (Norway); Orheim, Tone E.D. [Oslo University Hospital, Interventional Centre, Oslo (Norway); Graff, Bjoern A. [Oslo University Hospital-Ullevaal, Department of Radiology and Nuclear Medicine, Oslo (Norway); Josefsen, Roger [Oslo University Hospital-Ullevaal, Department of Neurosurgery, Oslo (Norway); Kumar, Theresa [Oslo University Hospital-Ullevaal, Department of Pathology, Oslo (Norway)

2011-05-15

Conventional magnetic resonance (MR) imaging has limited capacity to differentiate between glioblastoma multiforme (GBM) and metastasis. The purposes of this study were: (1) to compare microvascular leakage (MVL), cerebral blood volume (CBV), and blood flow (CBF) in the distinction of metastasis from GBM using dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging (DSC-MRI), and (2) to estimate the diagnostic accuracy of perfusion and permeability MR imaging. A prospective study of 61 patients (40 GBMs and 21 metastases) was performed at 3 T using DSC-MRI. Normalized rCBV and rCBF from tumoral (rCBVt, rCBFt), peri-enhancing region (rCBVe, rCBFe), and by dividing the value in the tumor by the value in the peri-enhancing region (rCBVt/e, rCBFt/e), as well as MVL were calculated. Hemodynamic and histopathologic variables were analyzed statistically and Spearman/Pearson correlations. Receiver operating characteristic curve analysis was performed for each of the variables. The rCBVe, rCBFe, and MVL were significantly greater in GBMs compared with those of metastases. The optimal cutoff value for differentiating GBM from metastasis was 0.80 which implies a sensitivity of 95%, a specificity of 92%, a positive predictive value of 86%, and a negative predictive value of 97% for rCBVe ratio. We found a modest correlation between rCBVt and rCBFt ratios. MVL measurements in GBMs are significantly higher than those in metastases. Statistically, both rCBVe, rCBVt/e and rCBFe, rCBFt/e were useful in differentiating between GBMs and metastases, supporting the hypothesis that perfusion MR imaging can detect infiltration of tumor cells in the peri-enhancing region. (orig.)

Magnetic resonance imaging of urinary bladder carcinoma: tumor staging and gadolinium contrast-enhanced imaging

International Nuclear Information System (INIS)

Doringer, E.; Joos, H.; Forstner, R.; Schmoller, H.

1992-01-01

Forty-nine patients with urinary bladder carcinomas underwent pre-operative examinations using magnetic resonance (MR) imaging. The results of the MR examinations were correlated with the clinical-pathological findings following transurethral resection (TUR) and bimanual palpation (n = 47) or radical cystectomy (n = 2). The results of pre-contrast MR tumor staging (T1, T2), viewing stages Tis-T2 collectively, and subsequent to separate assessments of stages T3b-T4b, were correct 76.6% of the time. Gadolinium-DTPA (Gd-DTPA) contrast-enhanced examinations (pre-contrast T1 and after Gd-DTPA) showed a staging accuracy rate of 85.7%. T2-weighted images did not indicate any advantage when compared to T1-weighted images following Gd-DTPA. The signal intensity ratios of tumor/fat and tumor/muscle tissue were measured on T1-weighted pre-contrast images and following Gd-DTPA and then evaluated statistically, whereby the increased tumor signal intensity was statistically significant (Wilcoxon test, P < 0.01). Due to the relatively short examination time needed for T1-weighted images and the specific tumor enhancement, the administration of Gd-DTPA proves valuable in the diagnosis of bladder carcinomas. T2-weighted images are not necessary. (orig.)

Dual antibody therapy to harness the innate anti-tumor immune response to enhance antibody targeting of tumors.

Science.gov (United States)

Chester, Cariad; Marabelle, Aurelien; Houot, Roch; Kohrt, Holbrook E

2015-04-01

Cancer immunotherapy is a rapidly evolving field that offers a novel paradigm for cancer treatment: therapies focus on enhancing the immune system's innate and adaptive anti-tumor response. Early immunotherapeutics have achieved impressive clinical outcomes and monoclonal antibodies are now integral to therapeutic strategies in a variety of cancers. However, only recently have antibodies targeting innate immune cells entered clinical development. Innate immune effector cells play important roles in generating and maintaining antitumor immunity. Antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) are important innate immune mechanisms for tumor eradication. These cytolytic processes are initiated by the detection of a tumor-targeting antibody and can be augmented by activating co-stimulatory pathways or blocking inhibitory signals on innate immune cells. The combination of FDA-approved monoclonal antibodies with innate effector-targeting antibodies has demonstrated potent preclinical therapeutic synergy and early-phase combinatorial clinical trials are ongoing. Copyright © 2015 Elsevier Ltd. All rights reserved.

Spinal cord injury-induced immune deficiency syndrome enhances infection susceptibility dependent on lesion level.

Science.gov (United States)

Brommer, Benedikt; Engel, Odilo; Kopp, Marcel A; Watzlawick, Ralf; Müller, Susanne; Prüss, Harald; Chen, Yuying; DeVivo, Michael J; Finkenstaedt, Felix W; Dirnagl, Ulrich; Liebscher, Thomas; Meisel, Andreas; Schwab, Jan M

2016-03-01

Pneumonia is the leading cause of death after acute spinal cord injury and is associated with poor neurological outcome. In contrast to the current understanding, attributing enhanced infection susceptibility solely to the patient's environment and motor dysfunction, we investigate whether a secondary functional neurogenic immune deficiency (spinal cord injury-induced immune deficiency syndrome, SCI-IDS) may account for the enhanced infection susceptibility. We applied a clinically relevant model of experimental induced pneumonia to investigate whether the systemic SCI-IDS is functional sufficient to cause pneumonia dependent on spinal cord injury lesion level and investigated whether findings are mirrored in a large prospective cohort study after human spinal cord injury. In a mouse model of inducible pneumonia, high thoracic lesions that interrupt sympathetic innervation to major immune organs, but not low thoracic lesions, significantly increased bacterial load in lungs. The ability to clear the bacterial load from the lung remained preserved in sham animals. Propagated immune susceptibility depended on injury of central pre-ganglionic but not peripheral postganglionic sympathetic innervation to the spleen. Thoracic spinal cord injury level was confirmed as an independent increased risk factor of pneumonia in patients after motor complete spinal cord injury (odds ratio = 1.35, P spinal cord injury directly causes increased risk for bacterial infection in mice as well as in patients. Besides obvious motor and sensory paralysis, spinal cord injury also induces a functional SCI-IDS ('immune paralysis'), sufficient to propagate clinically relevant infection in an injury level dependent manner. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Dural invasion of meningiomas adjacent to the tumor margin on Gd-DTPA-enhanced MR images: histopathologic correlation

International Nuclear Information System (INIS)

Hutzelmann, A.; Palmie, S.; Freund, M.; Heller, M.; Buhl, R.

1998-01-01

In intracranial meningiomas a flat, contrast-enhancing, dural structure adjacent to the tumor can occasionally be observed on gadolinium-DTPA-enhanced MR images. We wished to evaluate whether there is a correlation between MR images and meningeal invasion of intracranial meningiomas. The study included 54 patients with intracranial meningioma and the meningeal sign. MR studies included T2-weighted and gadolinium-DTPA-enhanced T1-weighted images in axial, coronal, and sagittal planes. Histopathologic examinations were done on the meningiomas adjacent to the dura mater. The meningeal sign on MRI was observed from 2 up to 35 mm from the main tumor mass in 31 (57 %) of the 54 patients. In 20 of these 31 the histopathologic examination showed tumor invasion, while 11 patients had no tumor invasion but tissue proliferation, hypervascularity, and vascular dilatation. Seven of the 23 meningiomas without the meningeal sign had histologically proven infiltration of the adjacent dura. MR imaging is not able to determine definitive whether or not there is dural infiltration of the meningiomas. In conclusion, resection of the tumor with a wide margin is necessary to achieve complete excision of meningioma and to avoid recurrence. (orig.)

Immunotherapy with Dendritic Cells Modified with Tumor-Associated Antigen Gene Demonstrates Enhanced Antitumor Effect Against Lung Cancer

Directory of Open Access Journals (Sweden)

Tao Jiang

2017-04-01

Full Text Available BACKGROUND: Immunotherapy using dendritic cell (DC vaccine has the potential to overcome the bottleneck of cancer therapy. METHODS: We engineered Lewis lung cancer cells (LLCs and bone marrow–derived DCs to express tumor-associated antigen (TAA ovalbumin (OVA via lentiviral vector plasmid encoding OVA gene. We then tested the antitumor effect of modified DCs both in vitro and in vivo. RESULTS: The results demonstrated that in vitro modified DCs could dramatically enhance T-cell proliferation (P < .01 and killing of LLCs than control groups (P < .05. Moreover, modified DCs could reduce tumor size and prolong the survival of LLC tumor-bearing mice than control groups (P < .01 and P < .01, respectively. Mechanistically, modified DCs demonstrated enhanced homing to T-cell–rich compartments and triggered more naive T cells to become cytotoxic T lymphocytes, which exhibited significant infiltration into the tumors. Interestingly, modified DCs also markedly reduced tumor cells harboring stem cell markers in mice (P < .05, suggesting the potential role on cancer stem-like cells. CONCLUSION: These findings suggested that DCs bioengineered with TAA could enhance antitumor effect and therefore represent a novel anticancer strategy that is worth further exploration.

Role of Gd-DTPA enhanced fat-suppression MR imaging on ovarian tumors

International Nuclear Information System (INIS)

Kang, Heoung Keun; Moon, Woong Jae; Seo, Jeong Jin; Kim, Jae Kyu; Park, Jin Gyoon; Choi, Ho Sun

1995-01-01

To determine the value of Gd-DTPA enhanced fat-suppression (GEFS) MR imaging in the characterization and differentiation of benign from malignant ovarian tumors. MRI findings of thirty-seven patients with surgically proved 44 ovarian tumors (30 benign, 14 malignant) were studied retrospectively. MR imaging with conventional spin echo (CSE; T1-weighted image TR/TE 450/20, T2-weighted image TR/TE 3500/30, 90) and GEFS were performed with a 1.5T GE signa. MRI findings of tumors including cystic or solid, wall and septal thickness, necrosis, invasion to adjacent organ, ascites and lymphadenopathy were assessed separately by using CSE and GEFS images, and then tumors were characterized as benign or malignant. Compared with CSE image, GEFS MR image showed better visualization of solid component in 5 malignant lesions, wall thickness in 5 malignant and 1 benign lesions, septal thickness in 3 malignant and 1 benign lesions, necrosis in 1 malignant lesion, and adjacent soft tissue invasion in 5 malignant lesions. Correct characterization of malignant tumors was increased from 71% on CSE image to 93% on GEFS image. However, correct characterization of benign tumors was 93% on both images. GEFS MR imaging could be useful for characterization of ovarian tumors, especially in malignant cases, and employed for differentiation of benign from malignant tumors

Comparative study of pulsed-continuous arterial spin labeling and dynamic susceptibility contrast imaging by histogram analysis in evaluation of glial tumors.

Science.gov (United States)

Arisawa, Atsuko; Watanabe, Yoshiyuki; Tanaka, Hisashi; Takahashi, Hiroto; Matsuo, Chisato; Fujiwara, Takuya; Fujiwara, Masahiro; Fujimoto, Yasunori; Tomiyama, Noriyuki

2018-06-01

Arterial spin labeling (ASL) is a non-invasive perfusion technique that may be an alternative to dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) for assessment of brain tumors. To our knowledge, there have been no reports on histogram analysis of ASL. The purpose of this study was to determine whether ASL is comparable with DSC-MRI in terms of differentiating high-grade and low-grade gliomas by evaluating the histogram analysis of cerebral blood flow (CBF) in the entire tumor. Thirty-four patients with pathologically proven glioma underwent ASL and DSC-MRI. High-signal areas on contrast-enhanced T 1 -weighted images or high-intensity areas on fluid-attenuated inversion recovery images were designated as the volumes of interest (VOIs). ASL-CBF, DSC-CBF, and DSC-cerebral blood volume maps were constructed and co-registered to the VOI. Perfusion histogram analyses of the whole VOI and statistical analyses were performed to compare the ASL and DSC images. There was no significant difference in the mean values for any of the histogram metrics in both of the low-grade gliomas (n = 15) and the high-grade gliomas (n = 19). Strong correlations were seen in the 75th percentile, mean, median, and standard deviation values between the ASL and DSC images. The area under the curve values tended to be greater for the DSC images than for the ASL images. DSC-MRI is superior to ASL for distinguishing high-grade from low-grade glioma. ASL could be an alternative evaluation method when DSC-MRI cannot be used, e.g., in patients with renal failure, those in whom repeated examination is required, and in children.

Natural killer cells and interleukin-1: a possible role in natural killer-tumor cell interaction

Energy Technology Data Exchange (ETDEWEB)

Traub, L M

1986-01-01

Effector cells with broad cytolytic reactivity against various tumor cell lines have been detected in the peripheral blood of normal individuals. This phenomenon, known as natural killing, appeared to be significantly depressed in a small group of patients with extensive primary hepatocellular carcinoma. These data, together with that of others showing depressed interleukin-1 (IL-1) production in these patients, were taken to indicate that IL-1 played a functional role in natural killer (NK) cell biology. The hypothesis was confirmed by the demonstration that preincubation of tumor target cells with IL-1 enhanced their susceptibility to NK cell killing. In this study tumor target cells were labelled with /sup 51/Cr.

Comparison of neuroendocrine tumor detection and characterization using DOTATOC-PET in correlation with contrast enhanced CT and delayed contrast enhanced MRI

International Nuclear Information System (INIS)

Giesel, F.L.; Kratochwil, C.; Mehndiratta, A.; Wulfert, S.; Moltz, J.H.; Zechmann, C.M.; Kauczor, H.U.; Haberkorn, U.; Ley, S.

2012-01-01

Purpose: We evaluated the rate of successful characterization of gastroenteropancreatic neuroendocrine tumors (NETs) present with an increased somatostatin receptor, comparing CE-CT with CE-MRI, each in correlation with DOTATOC-PET. Methods and materials: 8 patients with GEP-NET were imaged using CE-MRI (Gd-EOB-DTPA), CE-CT (Imeron 400) and DOTATOC-PET. Contrast-enhancement of normal liver-tissue and metastasis was quantified with ROI-technique. Tumor delineation was assessed with visual-score in blind-read-analysis by two experienced radiologists. Results: Out of 40 liver metastases in patients with NETs, all were detected by CE-MRI and the lesion extent could be adequately assessed, whereas CT failed to detect 20% of all metastases. The blind-read-score of CT in arterial and portal phase was median −0.65 and −1.4, respectively, and 2.7 for delayed-MRI. The quantitative ROI-analysis presented an improved contrast-enhancement-ratio with a median of 1.2, 1.6 and 3.3 for CE-CT arterial, portal-phase and delayed-MRI respectively. Conclusion: Late CE-MRI was superior to CE-CT in providing additionally morphologic characterization and exact lesion extension of hepatic metastases from neuroendocrine tumor detected with DOTATOC-PET. Therefore, late enhanced Gd-EOB-DTPA-MRI seems to be the adequate imaging modality for combination with DOTATOC-PET to provide complementary (macroscopic and molecular) tumor characterization in hepatic metastasized NETs

Enhancement of the RAD51 Recombinase Activity by the Tumor Suppressor PALB2

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Dray, Eloise; Etchin, Julia; Wiese, Claudia; Saro, Dorina; Williams, Gareth J.; Hammel, Michal; Yu, Xiong; Galkin, Vitold E.; Liu, Dongqing; Tsai, Miaw-Sheue; Sy, Shirley M-H.; Egelman, Edward; Chen, Junjie; Sung, Patrick; Schild, D.

2010-08-24

Homologous recombination mediated by the RAD51 recombinase helps eliminate chromosomal lesions, such as DNA double-stranded breaks induced by radiation or arising from injured DNA replication forks. The tumor suppressors BRCA2 and PALB2 act together to deliver RAD51 to chromosomal lesions to initiate repair. Here we document a new function of PALB2 in the enhancement of RAD51's ability to form the D-loop. We show that PALB2 binds DNA and physically interacts with RAD51. Importantly, while PALB2 alone stimulates D-loop formation, a cooperative effect is seen with RAD51AP1, an enhancer of RAD51. This stimulation stems from PALB2's ability to function with RAD51 and RAD51AP1 to assemble the synaptic complex. Our results help unveil a multi-faceted role of PALB2 in chromosome damage repair. Since PALB2 mutations can cause breast and other tumors or lead to Fanconi anemia, our findings are important for understanding the mechanism of tumor suppression in humans.

Polymorphism of the p53 tumor suppressor gene is associated with susceptibility to uterine leiomyoma.

Science.gov (United States)

Denschlag, Dominik; Bettendorf, Herta; Watermann, Dirk; Keck, Christoph; Tempfer, Clemens; Pietrowski, Detlef

2005-07-01

To evaluate the association between the presence of uterine leiomyoma and two single nuclear polymorphisms of the p53 tumor suppressor and the angiopoietin-2 (ANGPT2) genes. Prospective case control study. Academic research institution. One hundred thirty-two women with clinically and surgically diagnosed uterine leiomyomas and 280 controls. Peripheral venous puncture. Genotyping was performed by polymerase chain reaction-based amplification of the Arg and Pro variants at codon 72 of the p53 gene and by restriction fragment length polymorphism analysis of the G/G and G/A alleles in exon 4 of the ANGPT2 gene. Comparing women with uterine leiomyomas and controls, no statistically significant difference with respect to allele frequency and genotype distribution were ascertained for the ANGPT2 polymorphism (P=.2 and P=.5, respectively). However, for the p53 tumor suppressor gene polymorphism, statistically significant differences in terms of a higher Pro allele frequency and a higher prevalence of the Pro/Pro genotype among women with uterine leiomyoma (32.0% vs. 16.0%, respectively, and 21.3% vs. 4.7%, respectively) were ascertained (P=.001, OR 1.74; 95% CI 1.24-2.45, P=.001; OR 3.84, 95% CI 1.81-8.14; respectively). Carriage of the p53 polymorphism at codon 72 predicts the susceptibility to leiomyoma in a Caucasian population and may contribute to the pathogenesis of uterine leiomyoma.

Microwave irradiation of lignocellulosic materials, 4: Enhancement of enzymatic susceptibility of microwave-irradiated softwoods

International Nuclear Information System (INIS)

Azuma, J.; Higashino, J.; Isaka, M.; Koshijima, T.

1985-01-01

Effect of microwave irradiation on the enzymatic susceptibility of various softwoods was investigated. The pH values of the reaction liquor dropped with increasing temperature to 2.9-3.3 at 230°C, consistent with increase in acidity (0.5-0.85 meq at 230-239° C). Above approximately 180°C, hemicellulose underwent acid-mediated autohydrolysis and became water-soluble yielding a mixture of oligosaccharides and monosaccharides. The composition of water-soluble portion was similar for all wood species tested. The maximum extents of saccharification below 240°C ranged between 36-62% for softwoods, while those for hardwoods were between 88-93%. The present investigation confirmed that microwave pretreatment enhanced the enzymatic susceptibility of various softwoods. However, further attempt should be needed to give higher values equal to those for hardwoods. (author)

Perfusion characteristics of parotid gland tumors evaluated by contrast-enhanced ultrasound

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Klotz, Laura V., E-mail: Laura.Klotz@med.uni-muenchen.de [Department of Surgery, University of Munich, Munich (Germany); Gürkov, Robert [Department of Otorhinolaryngology, University of Munich, Munich (Germany); Eichhorn, Martin E. [Department of Surgery, University of Munich, Munich (Germany); Siedek, Vanessa; Krause, Eike [Department of Otorhinolaryngology, University of Munich, Munich (Germany); Jauch, Karl-Walter [Department of Surgery, University of Munich, Munich (Germany); Reiser, Maximilian F.; Clevert, Dirk-Andre [Department of Clinical Radiology, University of Munich, Munich (Germany)

2013-12-01

Purpose: Contrast enhanced ultrasound (CE-US) is a promising imaging modality for non-invasive analysis of parotid gland lesions because their vascularisation differs from normal gland tissue. This clinical study should further investigate CE-US as a diagnostic tool for parotid gland tumors. Materials and methods: 39 patients underwent CE-US measurements after intravenous application of a contrast agent (SonoVue, Bracco, Italy) before surgical tumor resection. Time–intensity curves gradients were calculated and parameters of intratumoral microcirculation were analysed. The vascularisation parameters were compared among the different tumor entities as defined per definitive histological diagnosis. Results: Histological analyses revealed 17 pleomorphic adenoma, 15 cystadenolymphoma and 7 malignoma. A significant difference of area below intensity time curve (AUC) and mean transit time (MTT) was measured in the malignant lesions compared to benign tumors (p < 0.05). A significant difference of AUC and maximum of signal increase (ΔSI{sub max}) for pleomorphic adenoma versus cystadenolymphoma was found (p < 0.05). Conclusion: CE-US seems to be a quantitative and independent method for the assessment of malign and benign parotid gland tumors. Further studies and clinical experience will have to validate this method as a reliable diagnostic tool that facilitates preoperative planning.

Radiation enhancement effect of RNA interference for HIF-1α on the transplant tumor

International Nuclear Information System (INIS)

Ren Ruimei; Sun Xindong; Zhao Hanxi; Yan Qingxia; Huang Guangwu

2008-01-01

Objective: To determine and explore the radiation enhancement of RNA interference for HIF-1α on the transplant tumor using polycationic polyethylenimine (PEI), as a new kind of gene vector. Methods: SPCA-1 nude mouse model was used. 160 nude mice bearing SPCA-1 were randomly divided into 4 treated groups and 1 control groups, each group had 32 mice. The expression of HIF-1α was studied by immunohistochemical method after RNA interference for HIF-1α. The differences of the volume, weight, survival time of the transplant tumor were studied among the simple radiation group, the simple RNA interference for HIF- 1α group and the combination of radiation and RNA interference for HIF-1α. Results: The expression of HIF-1α was decreased after RNA interference for HIF-1α. RNA interference for HIF-1α combined with radiation decreased the volume, weight of the transplant tumor, and prolonged its survival time period significantly than other methods. Conclusions: RNA interference targeting HIF-1α might enhance the radiosensitivity of the transplant tumor using PEI as a new kind of gene vector in vitro. (authors)

Genetic susceptibility to radiation: which impact on medical practice?

Energy Technology Data Exchange (ETDEWEB)

Alapetite, C.; Cosset, J.M. [Institut Curie, Dept. de Radiotherapie, 75 - Paris (France); Bourguignon, M.H.; Masse, R. [Office de Protection contre les Rayonnements Ionisants, 78 - le Vesinet (France)

2001-07-01

Recent progress especially in the field of gene identification and expression have raised more attention on genetic susceptibility to cancer possibly enhanced by radiations. Radiation therapists are mostly concerned by this question since hypersensitive patients may suffer from adverse effects in normal tissues following a standard radiation therapy and normally sensitive patients could benefit from higher doses of radiations for a better cure of their malignant tumors. Although only a small percentage of individuals are 'hypersensitive' to radiation effects, all medical specialists using ionising radiations should be aware of these new progress in medical knowledge. The present paper reviews the main pathologies (diseases, syndromes...) known or strongly suspected to be associated with a hypersensitivity to ionizing radiations. Then the main tests capable to detect in advance such pathologies are analyzed and compared. Finally guidelines are provided, especially to the radiation therapists to limit the risk of severe complications (or even deaths) for these specific subset of patients suffering from a genetic disorder with a susceptibility to radiations. (author)

Genetic susceptibility to radiation: which impact on medical practice?

International Nuclear Information System (INIS)

Alapetite, C.; Cosset, J.M.; Bourguignon, M.H.; Masse, R.

2001-01-01

Recent progress especially in the field of gene identification and expression have raised more attention on genetic susceptibility to cancer possibly enhanced by radiations. Radiation therapists are mostly concerned by this question since hypersensitive patients may suffer from adverse effects in normal tissues following a standard radiation therapy and normally sensitive patients could benefit from higher doses of radiations for a better cure of their malignant tumors. Although only a small percentage of individuals are 'hypersensitive' to radiation effects, all medical specialists using ionising radiations should be aware of these new progress in medical knowledge. The present paper reviews the main pathologies (diseases, syndromes...) known or strongly suspected to be associated with a hypersensitivity to ionizing radiations. Then the main tests capable to detect in advance such pathologies are analyzed and compared. Finally guidelines are provided, especially to the radiation therapists to limit the risk of severe complications (or even deaths) for these specific subset of patients suffering from a genetic disorder with a susceptibility to radiations. (author)

Systemic Administration of Interleukin 2 Enhances the Therapeutic Efficacy of Dendritic Cell-Based Tumor Vaccines

Science.gov (United States)

Shimizu, K.; Fields, R. C.; Giedlin, M.; Mule, J. J.

1999-03-01

We have reported previously that murine bone marrow-derived dendritic cells (DC) pulsed with whole tumor lysates can mediate potent antitumor immune responses both in vitro and in vivo. Because successful therapy was dependent on host immune T cells, we have now evaluated whether the systemic administration of the T cell stimulatory/growth promoting cytokine interleukin-2 (IL-2) could enhance tumor lysate-pulsed DC-based immunizations to further promote protective immunity toward, and therapeutic rejection of, syngeneic murine tumors. In three separate approaches using a weakly immunogenic sarcoma (MCA-207), the systemic administration of non-toxic doses of recombinant IL-2 (20,000 and 40,000 IU/dose) was capable of mediating significant increases in the potency of DC-based immunizations. IL-2 could augment the efficacy of tumor lysate-pulsed DC to induce protective immunity to lethal tumor challenge as well as enhance splenic cytotoxic T lymphocyte activity and interferon-γ production in these treated mice. Moreover, treatment with the combination of tumor lysate-pulsed DC and IL-2 could also mediate regressions of established pulmonary 3-day micrometastases and 7-day macrometastases as well as established 14- and 28-day s.c. tumors, leading to either significant cure rates or prolongation in overall survival. Collectively, these findings show that nontoxic doses of recombinant IL-2 can potentiate the antitumor effects of tumor lysate-pulsed DC in vivo and provide preclinical rationale for the use of IL-2 in DC-based vaccine strategies in patients with advanced cancer.

Nilotinib Enhances Tumor Angiogenesis and Counteracts VEGFR2 Blockade in an Orthotopic Breast Cancer Xenograft Model with Desmoplastic Response

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Sara Zafarnia

2017-11-01

Full Text Available Vascular endothelial growth factor (VEGF/VEGF receptor (VEGFR-targeted therapies predominantly affect nascent, immature tumor vessels. Since platelet-derived growth factor receptor (PDGFR blockade inhibits vessel maturation and thus increases the amount of immature tumor vessels, we evaluated whether the combined PDGFR inhibition by nilotinib and VEGFR2 blockade by DC101 has synergistic therapy effects in a desmoplastic breast cancer xenograft model. In this context, besides immunohistological evaluation, molecular ultrasound imaging with BR55, the clinically used VEGFR2-targeted microbubbles, was applied to monitor VEGFR2-positive vessels noninvasively and to assess the therapy effects on tumor angiogenesis. DC101 treatment alone inhibited tumor angiogenesis, resulting in lower tumor growth and in significantly lower vessel density than in the control group after 14 days of therapy. In contrast, nilotinib inhibited vessel maturation but enhanced VEGFR2 expression, leading to markedly increased tumor volumes and a significantly higher vessel density. The combination of both drugs led to an almost similar tumor growth as in the DC101 treatment group, but VEGFR2 expression and microvessel density were higher and comparable to the controls. Further analyses revealed significantly higher levels of tumor cell–derived VEGF in nilotinib-treated tumors. In line with this, nilotinib, especially in low doses, induced an upregulation of VEGF and IL-6 mRNA in the tumor cells in vitro, thus providing an explanation for the enhanced angiogenesis observed in nilotinib-treated tumors in vivo. These findings suggest that nilotinib inhibits vessel maturation but counteracts the effects of antiangiogenic co-therapy by enhancing VEGF expression by the tumor cells and stimulating tumor angiogenesis.

Susceptibility-Weighted Imaging and Quantitative Susceptibility Mapping in the Brain

Science.gov (United States)

Liu, Chunlei; Li, Wei; Tong, Karen A.; Yeom, Kristen W.; Kuzminski, Samuel

2015-01-01

Susceptibility-weighted imaging (SWI) is a magnetic resonance imaging (MRI) technique that enhances image contrast by using the susceptibility differences between tissues. It is created by combining both magnitude and phase in the gradient echo data. SWI is sensitive to both paramagnetic and diamagnetic substances which generate different phase shift in MRI data. SWI images can be displayed as a minimum intensity projection that provides high resolution delineation of the cerebral venous architecture, a feature that is not available in other MRI techniques. As such, SWI has been widely applied to diagnose various venous abnormalities. SWI is especially sensitive to deoxygenated blood and intracranial mineral deposition and, for that reason, has been applied to image various pathologies including intracranial hemorrhage, traumatic brain injury, stroke, neoplasm, and multiple sclerosis. SWI, however, does not provide quantitative measures of magnetic susceptibility. This limitation is currently being addressed with the development of quantitative susceptibility mapping (QSM) and susceptibility tensor imaging (STI). While QSM treats susceptibility as isotropic, STI treats susceptibility as generally anisotropic characterized by a tensor quantity. This article reviews the basic principles of SWI, its clinical and research applications, the mechanisms governing brain susceptibility properties, and its practical implementation, with a focus on brain imaging. PMID:25270052

Susceptibility-weighted imaging and quantitative susceptibility mapping in the brain.

Science.gov (United States)

Liu, Chunlei; Li, Wei; Tong, Karen A; Yeom, Kristen W; Kuzminski, Samuel

2015-07-01

Susceptibility-weighted imaging (SWI) is a magnetic resonance imaging (MRI) technique that enhances image contrast by using the susceptibility differences between tissues. It is created by combining both magnitude and phase in the gradient echo data. SWI is sensitive to both paramagnetic and diamagnetic substances which generate different phase shift in MRI data. SWI images can be displayed as a minimum intensity projection that provides high resolution delineation of the cerebral venous architecture, a feature that is not available in other MRI techniques. As such, SWI has been widely applied to diagnose various venous abnormalities. SWI is especially sensitive to deoxygenated blood and intracranial mineral deposition and, for that reason, has been applied to image various pathologies including intracranial hemorrhage, traumatic brain injury, stroke, neoplasm, and multiple sclerosis. SWI, however, does not provide quantitative measures of magnetic susceptibility. This limitation is currently being addressed with the development of quantitative susceptibility mapping (QSM) and susceptibility tensor imaging (STI). While QSM treats susceptibility as isotropic, STI treats susceptibility as generally anisotropic characterized by a tensor quantity. This article reviews the basic principles of SWI, its clinical and research applications, the mechanisms governing brain susceptibility properties, and its practical implementation, with a focus on brain imaging. © 2014 Wiley Periodicals, Inc.

Disruption of tumor neovasculature by microbubble enhanced ultrasound: a potential new physical therapy of anti-angiogenesis.

Science.gov (United States)

Liu, Zheng; Gao, Shunji; Zhao, Yang; Li, Peijing; Liu, Jia; Li, Peng; Tan, Kaibin; Xie, Feng

2012-02-01

Tumor angiogenesis is of vital importance to the growth and metastasis of solid tumors. The angiogenesis is featured with a defective, leaky and fragile vascular construction. Microbubble enhanced ultrasound (MEUS) cavitation is capable of mechanical disruption of small blood vessels depending on effective acoustic pressure amplitude. We hypothesized that acoustic cavitation combining high-pressure amplitude pulsed ultrasound (US) and circulating microbubble could potentially disrupt tumor vasculature. A high-pressure amplitude, pulsed ultrasound device was developed to induce inertial cavitation of circulating microbubbles. The tumor vasculature of rat Walker 256 was insonated percutaneously with two acoustic pressures, 2.6 MPa and 4.8 MPa, both with intravenous injection of a lipid microbubble. The controls were treated by the ultrasound only or sham ultrasound exposure. Contrast enhanced ultrasound (CEUS) and histology were performed to assess tumor circulation and pathological changes. The CEUS results showed that the circulation of Walker 256 tumors could be completely blocked off for 24 hours in 4.8 MPa treated tumors. The CEUS gray scale value (GSV) indicated that there was significant GSV drop-off in both of the two experimental groups but none in the controls. Histology showed that the tumor microvasculature was disrupted into diffuse hematomas accompanied by thrombosis, intercellular edema and multiple cysts formation. The 24 hours of tumor circulation blockage resulted in massive necrosis of the tumor. MEUS provides a new, simple physical method for anti-angiogenic therapy and may have great potential for clinical applications. Copyright © 2012 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Increased Tumor Oxygenation and Drug Uptake During Anti-Angiogenic Weekly Low Dose Cyclophosphamide Enhances the Anti-Tumor Effect of Weekly Tirapazamine

Science.gov (United States)

Doloff, J.C.; Khan, N.; Ma, J.; Demidenko, E.; Swartz, H.M.; Jounaidi, Y.

2010-01-01

Metronomic cyclophosphamide treatment is associated with anti-angiogenic activity and is anticipated to generate exploitable hypoxia using hypoxia-activated prodrugs. Weekly administration of tirapazamine (TPZ; 5 mg/kg body weight i.p.) failed to inhibit the growth of 9L gliosarcoma tumors grown s.c. in scid mice. However, the anti-tumor effect of weekly cyclophosphamide (CPA) treatment (140 mg/kg BW i.p.) was substantially enhanced by weekly TPZ administration. An extended tumor free period and increased frequency of tumor eradication without overt toxicity were observed when TPZ was given 3, 4 or 5 days after each weekly CPA treatment. Following the 2nd CPA injection, Electron Paramagnetic Resonance (EPR) Oximetry indicated significant increases in tumor pO2, starting at 48 hr, which further increased after the 3rd CPA injection. pO2 levels were, however, stable in growing untreated tumors. A strong negative correlation (−0.81) between tumor pO2 and tumor volume during 21 days of weekly CPA chemotherapy was observed, indicating increasing tumor pO2 with decreasing tumor volume. Furthermore, CPA treatment resulted in increased tumor uptake of activated CPA. CPA induced increases in VEGF RNA, which reached a maximum on day 1, and in PLGF RNA which was sustained throughout the treatment, while anti-angiogenic host thrombospondin-1 increased dramatically through day 7 post-CPA treatment. Weekly cyclophosphamide treatment was anticipated to generate exploitable hypoxia. However, our findings suggest that weekly CPA treatment induces a functional improvement of tumor vasculature, which is characterized by increased tumor oxygenation and drug uptake in tumors, thus counter-intuitively, benefiting intratumoral activation of TPZ and perhaps other bioreductive drugs. PMID:19754361

Reovirus FAST Protein Enhances Vesicular Stomatitis Virus Oncolytic Virotherapy in Primary and Metastatic Tumor Models

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Fabrice Le Boeuf

2017-09-01

Full Text Available The reovirus fusion-associated small transmembrane (FAST proteins are the smallest known viral fusogens (∼100–150 amino acids and efficiently induce cell-cell fusion and syncytium formation in multiple cell types. Syncytium formation enhances cell-cell virus transmission and may also induce immunogenic cell death, a form of apoptosis that stimulates immune recognition of tumor cells. These properties suggest that FAST proteins might serve to enhance oncolytic virotherapy. The oncolytic activity of recombinant VSVΔM51 (an interferon-sensitive vesicular stomatitis virus [VSV] mutant encoding the p14 FAST protein (VSV-p14 was compared with a similar construct encoding GFP (VSV-GFP in cell culture and syngeneic BALB/c tumor models. Compared with VSV-GFP, VSV-p14 exhibited increased oncolytic activity against MCF-7 and 4T1 breast cancer spheroids in culture and reduced primary 4T1 breast tumor growth in vivo. VSV-p14 prolonged survival in both primary and metastatic 4T1 breast cancer models, and in a CT26 metastatic colon cancer model. As with VSV-GFP, VSV-p14 preferentially replicated in vivo in tumors and was cleared rapidly from other sites. Furthermore, VSV-p14 increased the numbers of activated splenic CD4, CD8, natural killer (NK, and natural killer T (NKT cells, and increased the number of activated CD4 and CD8 cells in tumors. FAST proteins may therefore provide a multi-pronged approach to improving oncolytic virotherapy via syncytium formation and enhanced immune stimulation.

Enhancement of hypoxia-activated prodrug TH-302 anti-tumor activity by Chk1 inhibition.

Science.gov (United States)

Meng, Fanying; Bhupathi, Deepthi; Sun, Jessica D; Liu, Qian; Ahluwalia, Dharmendra; Wang, Yan; Matteucci, Mark D; Hart, Charles P

2015-05-21

The hypoxia-activated prodrug TH-302 is reduced at its nitroimidazole group and selectively under hypoxic conditions releases the DNA cross-linker bromo-isophosphoramide mustard (Br-IPM). Here, we have explored the effect of Chk1 inhibition on TH-302-mediated pharmacological activities. We employed in vitro cell viability, DNA damage, cellular signaling assays and the in vivo HT29 human tumor xenograft model to study the effect of Chk1inhibition on TH-302 antitumor activities. TH-302 cytotoxicity is greatly enhanced by Chk1 inhibition in p53-deficient but not in p53-proficient human cancer cell lines. Chk1 inhibitors reduced TH-302-induced cell cycle arrest via blocking TH-302-induced decrease of phosphorylation of histone H3 and increasing Cdc2-Y15 phosphorylation. Employing the single-cell gel electrophoresis (comet) assay, we observed a potentiation of the TH-302 dependent tail moment. TH-302 induced γH2AX and apoptosis were also increased upon the addition of Chk1 inhibitor. Potentiation of TH-302 cytotoxicity by Chk1 inhibitor was only observed in cell lines proficient in, but not deficient in homology-directed DNA repair. We also show that combination treatment led to lowering of Rad51 expression levels as compared to either agent alone. In vivo data demonstrate that Chk1 inhibitor enhances TH-302 anti-tumor activity in p53 mutant HT-29 human tumor xenografts, supporting the hypothesis that these in vitro results can translate to enhanced in vivo efficacy of the combination. TH-302-mediated in vitro and in vivo anti-tumor activities were greatly enhanced by the addition of Chk1 inhibitors. The preclinical data presented in this study support a new approach for the treatment of p53-deficient hypoxic cancers by combining Chk1 inhibitors with the hypoxia-activated prodrug TH-302.

Cytomegalovirus vector expressing RAE-1γ induces enhanced anti-tumor capacity of murine CD8+ T cells.

Science.gov (United States)

Tršan, Tihana; Vuković, Kristina; Filipović, Petra; Brizić, Ana Lesac; Lemmermann, Niels A W; Schober, Kilian; Busch, Dirk H; Britt, William J; Messerle, Martin; Krmpotić, Astrid; Jonjić, Stipan

2017-08-01

Designing CD8 + T-cell vaccines, which would provide protection against tumors is still considered a great challenge in immunotherapy. Here we show the robust potential of cytomegalovirus (CMV) vector expressing the NKG2D ligand RAE-1γ as CD8 + T cell-based vaccine against malignant tumors. Immunization with the CMV vector expressing RAE-1γ, delayed tumor growth or even provided complete protection against tumor challenge in both prophylactic and therapeutic settings. Moreover, a potent tumor control in mice vaccinated with this vector can be further enhanced by blocking the immune checkpoints TIGIT and PD-1. CMV vector expressing RAE-1γ potentiated expansion of KLRG1 + CD8 + T cells with enhanced effector properties. This vaccination was even more efficient in neonatal mice, resulting in the expansion and long-term maintenance of epitope-specific CD8 + T cells conferring robust resistance against tumor challenge. Our data show that immunomodulation of CD8 + T-cell responses promoted by herpesvirus expressing a ligand for NKG2D receptor can provide a powerful platform for the prevention and treatment of CD8 + T-cell sensitive tumors. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Functional and morphological effects of diazepam and midazolam on tumor vasculature in the 9L gliosarcoma brain tumor model using dynamic susceptibility contrast MRI: a comparative study

Directory of Open Access Journals (Sweden)

Yan N

2017-10-01

Full Text Available Nuo Yan,1 Yuzhen Zheng,2 Cheng Yang1 1Second Department of Anesthesiology, The Affiliated Hospital to Logistics University of PAP, Tianjin, 2Department of Anesthesiology, Tianjin Huanhu Hospital, Tianjin, China Abstract: Antiangiogenic therapy attenuates tumor growth by reducing vascularization. Diazepam (DZP and midazolam (MZL have antiangiogenic properties in human umbilical vein endothelial cells. Thus, we investigated the antiangiogenic activity of DZP and MZL in the rat 9L gliosarcoma brain tumor model. The effect on tumor vasculature was evaluated using dynamic susceptibility contrast magnetic resonance imaging with gradient-echo (GE and spin-echo (SE to assess perfusion parameters, including cerebral blood volume (CBV, cerebral blood flow (CBF, mean transit time (MTT, and mean vessel diameter. The GE-normalized CBF (nCBF in the tumors of untreated controls was significantly lower than that in normal brain tissue, whereas the CBV and MTT were higher. DZP- and MZL-treated rats had higher CBF and lower CBV and MTT values than did untreated controls. The tumor size decreased significantly to 33.5% in DZP-treated rats (P<0.001 and 22.5% in MZL-treated rats (P<0.01 relative to controls. The SE-normalized CBV was lower in DZP-treated (32.9% and MZL-treated (10.6% rats compared with controls. The mean vessel diameter decreased significantly by 32.5% in DPZ-treated and by 24.9% in MZL-treated rats compared with controls (P<0.01. The GE and SE nCBF values were higher in DZP-treated (49.9% and 40.1%, respectively and MZL-treated (41.2% and 32.1%, respectively rats than in controls. The GE- and SE-normalized MTTs were lower in DZP-treated (48.2% and 59.8%, respectively and MZL-treated (40.5% and 51.2%, respectively rats than in controls. Both DZP and MZL had antiangiogenic effects on tumor perfusion and vasculature; however, the antiangiogenic activity of DZP is more promising than that of MZL. Keywords: diazepam, midazolam, 9L gliosarcoma

Efficacy of dynamic susceptibility contrast MRI using echo-planar imaging in differential diagnosis of breast tumors

International Nuclear Information System (INIS)

Yoshino, Ayako

1998-01-01

It has been shown that T1-weighted dynamic MR imaging is a useful method in differentiating malignant breast tumors from benign lesions. Invasive breast carcinomas enhance more rapidly than benign lesions such as fibroadenomas, papillomas, and proliferative fibrocystic diseases. However, significant overlap in the dynamic profile of benign and malignant lesions may occur, resulting in relatively low specificity, which is an inherent limitation of this technique. The author attempted to improve diagnostic accuracy by utilizing dynamic susceptibility contrast MR imaging (DSC-MRI) with a single-shot echo-planar imaging sequence. Twenty-two patients underwent DSC-MRI using a 1.5-T unit (Magnetom Vision, Siemens). Images were obtained before, during and after the bolus injection of 20 mL of gadopentetate dimeglumine. The signal reduction rate within the first 30 seconds (ΔRT2) was calculated by the following equation: ΔRT2 = (postcontrast signal intensity-precontrast signal intensity) /precontrast signal intensity. A rapid, strong decrease in signal intensity was observed on the first pass of the contrast material in all cases of carcinoma, whereas no or only a minimal decrease in signal intensity was observed in all but one of the benign lesions. This method seems to be more accurate than T1-weighted dynamic MR imaging in the differentiation benign and malignant breast lesions. Since DSC-MRI can be performed quickly, subsequent conventional T1-weighted imaging can provide additional information about the morphologic features of lesions, to further support the diagnosis. In conclusion, DSC-MRI seems to be a promising method for the accurate preoperative assessment of breast lesions. (author)

Efficacy of dynamic susceptibility contrast MRI using echo-planar imaging in differential diagnosis of breast tumors

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Yoshino, Ayako [Kyorin Univ., Mitaka, Tokyo (Japan). School of Medicine

1998-07-01

It has been shown that T1-weighted dynamic MR imaging is a useful method in differentiating malignant breast tumors from benign lesions. Invasive breast carcinomas enhance more rapidly than benign lesions such as fibroadenomas, papillomas, and proliferative fibrocystic diseases. However, significant overlap in the dynamic profile of benign and malignant lesions may occur, resulting in relatively low specificity, which is an inherent limitation of this technique. The author attempted to improve diagnostic accuracy by utilizing dynamic susceptibility contrast MR imaging (DSC-MRI) with a single-shot echo-planar imaging sequence. Twenty-two patients underwent DSC-MRI using a 1.5-T unit (Magnetom Vision, Siemens). Images were obtained before, during and after the bolus injection of 20 mL of gadopentetate dimeglumine. The signal reduction rate within the first 30 seconds ({Delta}RT2) was calculated by the following equation: {Delta}RT2 (postcontrast signal intensity-precontrast signal intensity) /precontrast signal intensity. A rapid, strong decrease in signal intensity was observed on the first pass of the contrast material in all cases of carcinoma, whereas no or only a minimal decrease in signal intensity was observed in all but one of the benign lesions. This method seems to be more accurate than T1-weighted dynamic MR imaging in the differentiation benign and malignant breast lesions. Since DSC-MRI can be performed quickly, subsequent conventional T1-weighted imaging can provide additional information about the morphologic features of lesions, to further support the diagnosis. In conclusion, DSC-MRI seems to be a promising method for the accurate preoperative assessment of breast lesions. (author)

Equal pain – Unequal fear response: Enhanced susceptibility of tooth pain to fear conditioning

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Michael Lukas Meier

2014-07-01

Full Text Available Experimental fear conditioning in humans is widely used as a model to investigate the neural basis of fear learning and to unravel the pathogenesis of anxiety disorders. It has been observed that fear conditioning depends on stimulus salience and subject vulnerability to fear. It is further known that the prevalence of dental-related fear and phobia is exceedingly high in the population. Dental phobia is unique as no other body part is associated with a specific phobia. Therefore, we hypothesized that painful dental stimuli exhibit an enhanced susceptibility to fear conditioning when comparing to equal perceived stimuli applied to other body sites. Differential susceptibility to pain-related fear was investigated by analyzing responses to an unconditioned stimulus (UCS applied to the right maxillary canine (UCS-c versus the right tibia (UCS-t. For fear conditioning, UCS-c and USC-t consisted of painful electric stimuli, carefully matched at both application sites for equal intensity and quality perception. UCSs were paired to simple geometrical forms which served as conditioned stimuli (CS+. Unpaired CS+ were presented for eliciting and analyzing conditioned fear responses. Outcome parameter were 1 skin conductance changes and 2 time-dependent brain activity (BOLD responses in fear-related brain regions such as the amygdala, anterior cingulate cortex, insula, thalamus, orbitofrontal cortex and medial prefrontal cortex.A preferential susceptibility of dental pain to fear conditioning was observed, reflected by heightened skin conductance responses and enhanced time-dependent brain activity (BOLD responses in the fear network. For the first time, this study demonstrates fear-related neurobiological mechanisms that point towards a superior conditionability of tooth pain. Beside traumatic dental experiences our results offer novel evidence that might explain the high prevalence of dental-related fears in the population.

Contrast-enhanced multidetector computerized tomography for odontogenic cysts and cystic-appearing tumors of the jaws: is it useful?

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Kakimoto, Naoya; Chindasombatjaroen, Jira; Tomita, Seiki; Shimamoto, Hiroaki; Uchiyama, Yuka; Hasegawa, Yoko; Kishino, Mitsunobu; Murakami, Shumei; Furukawa, Souhei

2013-01-01

The purpose of this study was to investigate the usefulness of computerized tomography (CT), particularly contrast-enhanced CT, in differentiation of jaw cysts and cystic-appearing tumors. We retrospectively analyzed contrast-enhanced CT images of 90 patients with odontogenic jaw cysts or cystic-appearing tumors. The lesion size and CT values were measured and the short axis to long axis (S/L) ratio, contrast enhancement (CE) ratio, and standard deviation ratio were calculated. The lesion size and the S/L ratio of keratocystic odontogenic tumors were significantly different from those of radicular cysts and follicular cysts. There were no significant differences in the CE ratio among the lesions. Multidetector CT provided diagnostic information about the size of odontogenic cysts and cystic-appearing tumors of the jaws that was related to the lesion type, but showed no relation between CE ratio and the type of these lesions. Copyright © 2013 Elsevier Inc. All rights reserved.

Polyethylene Glycol Modified, Cross-Linked Starch Coated Iron Oxide Nanoparticles for Enhanced Magnetic Tumor Targeting

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Cole, Adam J.; David, Allan E.; Wang, Jianxin; Galbán, Craig J.; Hill, Hannah L.; Yang, Victor C.

2010-01-01

While successful magnetic tumor targeting of iron oxide nanoparticles has been achieved in a number of models, the rapid blood clearance of magnetically suitable particles by the reticuloendothelial system (RES) limits their availability for targeting. This work aimed to develop a long-circulating magnetic iron oxide nanoparticle (MNP) platform capable of sustained tumor exposure via the circulation and, thus, enhanced magnetic tumor targeting. Aminated, cross-linked starch (DN) and aminosilane (A) coated MNPs were successfully modified with 5 kDa (A5, D5) or 20 kDa (A20, D20) polyethylene glycol (PEG) chains using simple N-Hydroxysuccinimide (NHS) chemistry and characterized. Identical PEG-weight analogues between platforms (A5 & D5, A20 & D20) were similar in size (140–190 nm) and relative PEG labeling (1.5% of surface amines – A5/D5, 0.4% – A20/D20), with all PEG-MNPs possessing magnetization properties suitable for magnetic targeting. Candidate PEG-MNPs were studied in RES simulations in vitro to predict long-circulating character. D5 and D20 performed best showing sustained size stability in cell culture medium at 37°C and 7 (D20) to 10 (D5) fold less uptake in RAW264.7 macrophages when compared to previously targeted, unmodified starch MNPs (D). Observations in vitro were validated in vivo, with D5 (7.29 hr) and D20 (11.75 hr) showing much longer half-lives than D (0.12 hr). Improved plasma stability enhanced tumor MNP exposure 100 (D5) to 150 (D20) fold as measured by plasma AUC0-∞ Sustained tumor exposure over 24 hours was visually confirmed in a 9L-glioma rat model (12 mg Fe/kg) using magnetic resonance imaging (MRI). Findings indicate that both D5 and D20 are promising MNP platforms for enhanced magnetic tumor targeting, warranting further study in tumor models. PMID:21176955

Spin Lattice Relaxation EPR pO2 Images May Direct the Location of Radiation Tumor Boosts to Enhance Tumor Cure.

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Epel, Boris; Krzykawska-Serda, Martyna; Tormyshev, Victor; Maggio, Matthew C; Barth, Eugene D; Pelizzari, Charles A; Halpern, Howard J

2017-12-01

Radiation treatment success and high tumor oxygenation and success have been known to be highly correlated. This suggests that radiation therapy guided by images of tumor regions with low oxygenation, oxygen-guided radiation therapy (OGRT) may be a promising enhancement of cancer radiation treatment. Before applying the technique to human subjects, OGRT needs to be tested in animals, most easily in rodents. Electron paramagnetic resonance imaging provides quantitative maps of tissue and tumor oxygen in rodents with 1 mm spatial resolution and 1 torr pO 2 resolution at low oxygen levels. The difficulty of using mouse models is their small size and that of their tumors. To overcome this we used XRAD225Cx micro-CT/ therapy system and 3D printed conformal blocks. Radiation is delivered first to a uniform 15% tumor control dose for the whole tumor and then a boost dose to either hypoxic tumor regions or equal volumes of well oxygenated tumor. Delivery of the booster dose used a multiple beam angles to deliver radiation beams whose shape conforms to that of all hypoxic regions or fully avoids those regions. To treat/avoid all hypoxic regions we used individual radiation blocks 3D-printed from acrylonitrile butadiene styrene polymer infused with tungsten particles fabricated immediately after imaging to determine regions with pO 2 less than 10 torr. Preliminary results demonstrate the efficacy of the radiation treatment with hypoxic boosts with syngeneic FSa fibrosarcoma tumors in the legs of C3H mice.

Early-postoperative magnetic resonance imaging in glial tumors: prediction of tumor regrowth and recurrence

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Ekinci, Gazanfer; Akpinar, Ihsan N. E-mail: i.akpinar@mailcity.com; Baltacioglu, Feyyaz; Erzen, Canan; Kilic, Tuerker; Elmaci, Ilhan; Pamir, Necmettin

2003-02-01

Objective: This study investigated the value of early-postoperative magnetic resonance (EPMR) imaging in the detection of residual glial tumor and investigated the role of EPMR for the prediction of tumor regrowth and recurrence. Methods and materials: We retrospectively analyzed pre- and post-operative magnetic resonance imaging results from 50 adult patients who underwent surgical treatment for supratentorial glial tumor. There were glioblastoma multiforme in 25 patients, astrocytoma (grades II and III) in 11 patients, oligodendroglioma (grades II and III) in 9 patients, and oligoastrocytoma (grades II and III) in 5 patients. EPMR imaging was performed within 24 h after surgery. EPMR findings were compared with the neurosurgeon's intraoperative estimation of gross tumor removal. Patterns of contrast enhancement at the resection site, in residual and developing tumor tissue and blood at the resection site were evaluated on EPMR and in follow-up studies. 'Residual tumor' was defined as contrast enhancing mass at the operative site on EPMR. 'Regrowth' was defined as contrast enhancing mass detected on follow-up in the same location as the primary tumor. 'Recurrence' was defined as appearance of a mass lesion in the brain parenchyma distant from the resection bed during follow-up. Results: Nineteen patients showed no evidence of residual tumor, regrowth, or recurrence on EPMR or any of the later follow-up radiological examinations. EPMR identified 20 cases of residual tumor. Follow-up showed tumor regrowth in 10 patients, and tumor recurrence in 1 case. EPMR showed contrast enhancement of the resection bed in 45 of the 50 patients. Four of the 20 residual tumors showed a thick linear enhancement pattern, and the other 16 cases exhibited thick linear-nodular enhancement. No thin linear enhancement was observed in the residual tumor group. Nine of the 10-regrowth tumors showed a thick linear-nodular enhancement pattern, and one

Enhanced antitumor efficacy of cisplatin in combination with HemoHIM in tumor-bearing mice

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Kim Sung-Ho

2009-03-01

Full Text Available Abstract Background Although cisplatin is one of the most effective chemotherapeutic agents, cisplatin alone does not achieve a satisfactory therapeutic outcome. Also cisplatin accumulation shows toxicity to normal tissues. In this study, we examined the possibility of HemoHIM both to enhance anticancer effect with cisplatin and to reduce the side effects of cisplatin in melanoma-bearing mice. Methods HemoHIM was prepared by adding the ethanol-insoluble fraction to the total water extract of a mixture of 3 edible herbs, Angelica Radix, Cnidium Rhizoma and Paeonia Radix. Anticancer effects of HemoHIM with cisplatin were evaluated in melanoma-bearing mice. We used a Cr51-release assay to measure the activity of NK/Tc cell and ELISA to evaluate the production of cytokines. Results In melanoma-bearing mice, cisplatin (4 mg/kg B.W. reduced the size and weight of the solid tumors, and HemoHIM supplementation with cisplatin enhanced the decrease of both the tumor size (p in vitro, and did not disturb the effects of cisplatin in vitro. However HemoHIM administration enhanced both NK cell and Tc cell activity in mice. Interestingly, HemoHIM increased the proportion of NK cells in the spleen. In melanoma-bearing mice treated with cisplatin, HemoHIM administration also increased the activity of NK cells and Tc cells and the IL-2 and IFN-γ secretion from splenocytes, which seemed to contribute to the enhanced efficacy of cisplatin by HemoHIM. Also, HemoHIM reduced nephrotoxicity as seen by tubular cell of kidney destruction. Conclusion HemoHIM may be a beneficial supplement during cisplatin chemotherapy for enhancing the anti-tumor efficacy and reducing the toxicity of cisplatin.

Pancreatic neuroendocrine tumors containing areas of iso- or hypoattenuation in dynamic contrast-enhanced computed tomography: Spectrum of imaging findings and pathological grading.

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Hyodo, Ryota; Suzuki, Kojiro; Ogawa, Hiroshi; Komada, Tomohiro; Naganawa, Shinji

2015-11-01

To evaluate dynamic contrast-enhanced computed tomography (CT) features of pancreatic neuroendocrine tumors (PNETs) containing areas of iso- or hypoattenuation and the relationship with pathological grading. Between June 2006 and March 2014, 61 PNETs in 58 consecutive patients (29 male, 29 female; median-age 55 years), which were surgically diagnosed, underwent preoperative dynamic contrast-enhanced CT. PNETs were classified based on contrast enhancement patterns in the pancreatic phase: iso/hypo-PNETs were defined as tumors containing areas of iso- or hypoattenuation except for cystic components, and hyper-PNETs were tumors showing hyperattenuation over the whole area. CT findings and contrast-enhancement patterns of the tumors were evaluated retrospectively by two radiologists and compared with the pathological grading. Iso/hypo-PNETs comprised 26 tumors, and hyper-PNETs comprised 35 tumors. Not only hyper-PNETs but also most iso/hypo-PNETs showed peak enhancement in the pancreatic phase and a washout from the portal venous phase to the delayed phase. Iso/hypo-PNETs showed larger tumor size than the hyper-PNETs (mean, 3.7 cm vs. 1.6 cm; PIso/hypo-PNETs also showed significantly higher pathological grading (WHO 2010 classification; iso/hypo, G1=14, G2=11, G3=1; hyper, G1=34, G2=1; Piso/hypo-areas showed a rapid enhancement pattern as well as hyper-PNETs, various radiological features and higher malignant potential. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Content-based retrieval of brain tumor in contrast-enhanced MRI images using tumor margin information and learned distance metric.

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Yang, Wei; Feng, Qianjin; Yu, Mei; Lu, Zhentai; Gao, Yang; Xu, Yikai; Chen, Wufan

2012-11-01

A content-based image retrieval (CBIR) method for T1-weighted contrast-enhanced MRI (CE-MRI) images of brain tumors is presented for diagnosis aid. The method is thoroughly evaluated on a large image dataset. Using the tumor region as a query, the authors' CBIR system attempts to retrieve tumors of the same pathological category. Aside from commonly used features such as intensity, texture, and shape features, the authors use a margin information descriptor (MID), which is capable of describing the characteristics of tissue surrounding a tumor, for representing image contents. In addition, the authors designed a distance metric learning algorithm called Maximum mean average Precision Projection (MPP) to maximize the smooth approximated mean average precision (mAP) to optimize retrieval performance. The effectiveness of MID and MPP algorithms was evaluated using a brain CE-MRI dataset consisting of 3108 2D scans acquired from 235 patients with three categories of brain tumors (meningioma, glioma, and pituitary tumor). By combining MID and other features, the mAP of retrieval increased by more than 6% with the learned distance metrics. The distance metric learned by MPP significantly outperformed the other two existing distance metric learning methods in terms of mAP. The CBIR system using the proposed strategies achieved a mAP of 87.3% and a precision of 89.3% when top 10 images were returned by the system. Compared with scale-invariant feature transform, the MID, which uses the intensity profile as descriptor, achieves better retrieval performance. Incorporating tumor margin information represented by MID with the distance metric learned by the MPP algorithm can substantially improve the retrieval performance for brain tumors in CE-MRI.

Peculiarities in the CT findings of germ cell tumors in various tumor localizations

International Nuclear Information System (INIS)

Tazoe, Makoto; Miyagami, Mitsusuke; Tsubokawa, Takashi

1991-01-01

The CT findings of 17 germ cell tumors were studied in relation to the locations of the tumor, the pathological diagnoses, and the tumor markers (AFP and HCG). Generally, the CT findings of germ cell tumors depended on the pathological diagnoses more strongly than on the location of the tumors. On plain CT of 7 germ cell tumors in the pineal region, all of them demonstrated heterogeneous findings. Hydrocephalus was seen in 6 cases (86%) and calcification in 6 cases (86%) of the germ cell tumors in the pineal region. Calcification and hydrocephalus that appeared more often than in other regions were characteristic of germ cell tumors of the pineal region. The germ cell tumors in the basal ganglia had a slightly homogenous high density, with small cysts and calcification in most of them on plain CT. On enhanced CT, the tumors were moderately enhanced in all cases located in the basal ganglia. Four cases of germ cell tumors located in the basal ganglia revealed the dilatation of lateral ventricle due to hemispheric atrophy in the tumor side. The germ cell tumors showing an increase in the tumor markers such as AFP and HCG, which were usually malignant germ cell tumors, were strongly enhanced on enhanced CT. (author)

Au@Pt nanoparticles as catalase mimics to attenuate tumor hypoxia and enhance immune cell-mediated cytotoxicity

Science.gov (United States)

Liang, Hong; Wu, Ying; Ou, Xiang-Yu; Li, Jing-Ying; Li, Juan

2017-11-01

Hypoxic tumor microenvironment (TME) is closely linked to tumor progression, heterogeneity and immune suppression. Therefore, the development of effective methods to overcome hypoxia and substantially enhance the immunotherapy efficacy remains a desirable goal. Herein, we engineered a biocompatible Au core/Pt shell nanoparticles (Au@Pt NPs) to reoxygenate the TME by reacting with endogenous H2O2. Treatment with Au@Pt NPs appeared to improve oxygen in intracellular environments and decrease hypoxia-inducible factor-1α expression. Furthermore, the integration of high catalytic efficiency of Au@Pt NPs with cytokine-induced killer (CIK) cell immunotherapy, could lead to significantly improve the effect of CIK cell-mediated cytotoxicity. These results suggest great potential of Au@Pt NPs for regulation of the hypoxic TME and enhance immune cell mediated anti-tumor immunity.

Preliminary Study of Oxygen-Enhanced Longitudinal Relaxation in MRI: A Potential Novel Biomarker of Oxygenation Changes in Solid Tumors

International Nuclear Information System (INIS)

O'Connor, James P.B.; Naish, Josephine H.; Parker, Geoff J.M.; Waterton, John C.; Watson, Yvonne; Jayson, Gordon C.; Buonaccorsi, Giovanni A.; Cheung, Sue; Buckley, David L.; McGrath, Deirdre M.; West, Catharine M.L.; Davidson, Susan E.; Roberts, Caleb; Mills, Samantha J.; Mitchell, Claire L.; Hope, Lynn; Ton, N. Chan; Jackson, Alan

2009-01-01

Purpose: There is considerable interest in developing non-invasive methods of mapping tumor hypoxia. Changes in tissue oxygen concentration produce proportional changes in the magnetic resonance imaging (MRI) longitudinal relaxation rate (R 1 ). This technique has been used previously to evaluate oxygen delivery to healthy tissues and is distinct from blood oxygenation level-dependent (BOLD) imaging. Here we report application of this method to detect alteration in tumor oxygenation status. Methods and materials: Ten patients with advanced cancer of the abdomen and pelvis underwent serial measurement of tumor R 1 while breathing medical air (21% oxygen) followed by 100% oxygen (oxygen-enhanced MRI). Gadolinium-based dynamic contrast-enhanced MRI was then performed to compare the spatial distribution of perfusion with that of oxygen-induced ΔR 1 . Results: ΔR 1 showed significant increases of 0.021 to 0.058 s -1 in eight patients with either locally recurrent tumor from cervical and hepatocellular carcinomas or metastases from ovarian and colorectal carcinomas. In general, there was congruency between perfusion and oxygen concentration. However, regional mismatch was observed in some tumor cores. Here, moderate gadolinium uptake (consistent with moderate perfusion) was associated with low area under the ΔR 1 curve (consistent with minimal increase in oxygen concentration). Conclusions: These results provide evidence that oxygen-enhanced longitudinal relaxation can monitor changes in tumor oxygen concentration. The technique shows promise in identifying hypoxic regions within tumors and may enable spatial mapping of change in tumor oxygen concentration.

Ultrasonic enhancement of drug penetration in solid tumors

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Chun-yen eLai

2013-08-01

Full Text Available Increasing the penetration of drugs within solid tumors can be accomplished through multiple ultrasound-mediated mechanisms. The application of ultrasound can directly change the structure or physiology of tissues or can induce changes in a drug or vehicle in order to enhance delivery and efficacy. With each ultrasonic pulse, a fraction of the energy in the propagating wave is absorbed by tissue and results in local heating. When ultrasound is applied to achieve mild hyperthermia, the thermal effects are associated with an increase in perfusion or the release of a drug from a temperature-sensitive vehicle. Higher ultrasound intensities locally ablate tissue and result in increased drug accumulation surrounding the ablated region of interest. Further, the mechanical displacement induced by the ultrasound pulse can result in the nucleation, growth and collapse of gas bubbles. As a result of such cavitation, the permeability of a vessel wall or cell membrane can be increased. Finally, the radiation pressure of the propagating pulse can translate particles or tissues. In this perspective, we will review recent progress in ultrasound-mediated tumor delivery and the opportunities for clinical translation.

Low dose radiation enhancing inhibitory effect of tumor-associated antigen peptide extract on H-22 hepatocarcinoma

Energy Technology Data Exchange (ETDEWEB)

Zuyue, Sun; Jingyi, Fu; Yong, Zhao [Transplantation Biology Research Division, State Key Laboratory of Biomembrane and Membrane Biotechnology, Inst. of Zoology, Chinese Academy of Sciences, Beijing (China); Jianxiang, Liu; Zhibo, Fu; Xiuyi, Li; Shuzheng, Liu; Shouliang, Gong

2005-06-15

Objective: To determine whether there is synergically inhibitory effect of low dose radiation (LDR) and tumor-associated antigen peptides (TAP) on tumor growth in vivo, which may provide experimental basis for potential clinical co-application of these two approaches to treat cancers. Methods: TAP extract (MW {<=}3x10{sup 6}) from tumor cell membrane was prepared with mild acid elution method , as reported. The mice were whole-bodily irradiated with 75 mGy X-rays 12 h before immunization with TAP extract. After immunization , the levels of CD3, CD69, TCR{alpha}{beta} cells and T cell subsets in the spleen were detected with FACS. The tumor growth rate was estimated, and the responses to Con A, the cytokine productions and CTL activities of splenocytes were also analyzed 7 d after immunization with TAP. Results: The present experimental results showed that the TAP extract significantly reduced the incidence of the transplanted tumor, delayed the average appearing time and decreased the growth speed of the tumor. The response of splenocytes from mice immunized with TAP extract to Con A increased significantly compared with that in the control group. Irradiation with 75 mGy X-rays 12 h before immunization further enhanced the inhibitory effect of TAP extract on tumor growth, and increased the percentage of CD8{sup +} splenocytes. Conclusion: These results suggest that whole-body irradiation with LDR exerts a synergic inhibitory effect with TAP on tumor growth in vivo, in which enhanced cellular immune responses may be involved. (authors)

Inhibition of BRD4 suppresses tumor growth and enhances iodine uptake in thyroid cancer

International Nuclear Information System (INIS)

Gao, Xuemei; Wu, Xinchao; Zhang, Xiao; Hua, Wenjuan; Zhang, Yajing; Maimaiti, Yusufu; Gao, Zairong; Zhang, Yongxue

2016-01-01

Thyroid cancer is a common malignancy of the endocrine system. Although radioiodine "1"3"1I treatment on differentiated thyroid cancer is widely used, many patients still fail to benefit from "1"3"1I therapy. Therefore, exploration of novel targeted therapies to suppress tumor growth and improve radioiodine uptake remains necessary. Bromodomain-containing protein 4 (BRD4) is an important member of the bromodomain and extra terminal domain family that influences transcription of downstream genes by binding to acetylated histones. In the present study, we found that BRD4 was up-regulated in thyroid cancer tissues and cell lines. Inhibition of BRD4 in thyroid cancer cells by JQ1 resulted in cell cycle arrest at G0/G1 phase and enhanced "1"3"1I uptake in vitro and suppressed tumor growth in vivo. Moreover, JQ1 treatment suppressed C-MYC but enhanced NIS expression. We further demonstrated that BRD4 was enriched in the promoter region of C-MYC, which could be markedly blocked by JQ1 treatment. In conclusion, our findings revealed that the aberrant expression of BRD4 in thyroid cancer is possibly involved in tumor progression, and JQ1 is potentially an effective chemotherapeutic agent against human thyroid cancer. - Highlights: • BRD4 is upregulated in thyroid cancer tissues and cell lines. • Inhibition of BRD4 induced cell cycle arrest and enhanced radioiodine uptake in vitro and impaired tumor growth in vivo. • JQ1 suppressed the expression of C-MYC and promoted the expression of NIS and P21. • JQ1 attenuated the recruitment of BRD4 to MYC promoter in thyroid cancer.

Inhibition of BRD4 suppresses tumor growth and enhances iodine uptake in thyroid cancer

Energy Technology Data Exchange (ETDEWEB)

Gao, Xuemei [Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province (China); Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, Hubei Province (China); Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province (China); Wu, Xinchao [Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province (China); Zhang, Xiao; Hua, Wenjuan; Zhang, Yajing [Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province (China); Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, Hubei Province (China); Maimaiti, Yusufu [Department of Thyroid and Breast Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province (China); Gao, Zairong, E-mail: gaobonn@163.com [Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province (China); Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, Hubei Province (China); Zhang, Yongxue [Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province (China); Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, Hubei Province (China)

2016-01-15

Thyroid cancer is a common malignancy of the endocrine system. Although radioiodine {sup 131}I treatment on differentiated thyroid cancer is widely used, many patients still fail to benefit from {sup 131}I therapy. Therefore, exploration of novel targeted therapies to suppress tumor growth and improve radioiodine uptake remains necessary. Bromodomain-containing protein 4 (BRD4) is an important member of the bromodomain and extra terminal domain family that influences transcription of downstream genes by binding to acetylated histones. In the present study, we found that BRD4 was up-regulated in thyroid cancer tissues and cell lines. Inhibition of BRD4 in thyroid cancer cells by JQ1 resulted in cell cycle arrest at G0/G1 phase and enhanced {sup 131}I uptake in vitro and suppressed tumor growth in vivo. Moreover, JQ1 treatment suppressed C-MYC but enhanced NIS expression. We further demonstrated that BRD4 was enriched in the promoter region of C-MYC, which could be markedly blocked by JQ1 treatment. In conclusion, our findings revealed that the aberrant expression of BRD4 in thyroid cancer is possibly involved in tumor progression, and JQ1 is potentially an effective chemotherapeutic agent against human thyroid cancer. - Highlights: • BRD4 is upregulated in thyroid cancer tissues and cell lines. • Inhibition of BRD4 induced cell cycle arrest and enhanced radioiodine uptake in vitro and impaired tumor growth in vivo. • JQ1 suppressed the expression of C-MYC and promoted the expression of NIS and P21. • JQ1 attenuated the recruitment of BRD4 to MYC promoter in thyroid cancer.

Studies into the transplantation biology of ultraviolet light-induced tumors

International Nuclear Information System (INIS)

Daynes, R.A.; Spellman, C.W.; Woodward, J.G.; Stewart, D.A.

1977-01-01

The majority of skin tumors induced in mice by ultraviolet (uv) light are rejected when implanted into normal syngeneic recipients. Subcarcinogenic levels of uv light exposure render the normally resistant mice susceptible to tumor challenge. The immunoregulatory effect of uv light appears to be additive, since the growth rate of a tumor transplant is dependent upon the length of uv exposure administered prior to implantation. This suppressive influence does not appear to be directly mediated by the uv light, because the amputation of uv-irradiated tail skin allows for a retention of tumor resistance in otherwise tumor-susceptible hosts. uv-irradiated mice could also be immunized against uv tumors, which suggests that immune recognition of tumor-specific transplantation antigens has not been inhibited. The ability of uv exposure to alter normal immunological reactivity to uv-induced tumors is possibly an integral factor in the mechanism underlying uv carcinogenesis

Reduced expression IRF7 in nasal epithelial cells from smokers as a potential mechanism mediating enhanced susceptibility to influenza

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Rationale: Smokers are more susceptible to viral infections, including influenza virus, yet the mechanisms mediating this effect are not known. Methods: We have established an in vitro model of differentiated nasal epithelial cells from smokers, which maintain enhanced levels...

Enhanced antitumor efficacy of cisplatin in combination with HemoHIM in tumor-bearing mice.

Science.gov (United States)

Park, Hae-Ran; Ju, Eun-Jin; Jo, Sung-Kee; Jung, Uhee; Kim, Sung-Ho; Yee, Sung-Tae

2009-03-17

Although cisplatin is one of the most effective chemotherapeutic agents, cisplatin alone does not achieve a satisfactory therapeutic outcome. Also cisplatin accumulation shows toxicity to normal tissues. In this study, we examined the possibility of HemoHIM both to enhance anticancer effect with cisplatin and to reduce the side effects of cisplatin in melanoma-bearing mice. HemoHIM was prepared by adding the ethanol-insoluble fraction to the total water extract of a mixture of 3 edible herbs, Angelica Radix, Cnidium Rhizoma and Paeonia Radix. Anticancer effects of HemoHIM with cisplatin were evaluated in melanoma-bearing mice. We used a Cr51-release assay to measure the activity of NK/Tc cell and ELISA to evaluate the production of cytokines. In melanoma-bearing mice, cisplatin (4 mg/kg B.W.) reduced the size and weight of the solid tumors, and HemoHIM supplementation with cisplatin enhanced the decrease of both the tumor size (p HemoHIM itself did not inhibit melanoma cell growth in vitro, and did not disturb the effects of cisplatin in vitro. However HemoHIM administration enhanced both NK cell and Tc cell activity in mice. Interestingly, HemoHIM increased the proportion of NK cells in the spleen. In melanoma-bearing mice treated with cisplatin, HemoHIM administration also increased the activity of NK cells and Tc cells and the IL-2 and IFN-gamma secretion from splenocytes, which seemed to contribute to the enhanced efficacy of cisplatin by HemoHIM. Also, HemoHIM reduced nephrotoxicity as seen by tubular cell of kidney destruction. HemoHIM may be a beneficial supplement during cisplatin chemotherapy for enhancing the anti-tumor efficacy and reducing the toxicity of cisplatin.

Mycobacterium tuberculosis complex enhances susceptibility of CD4 T cells to HIV through a TLR2-mediated pathway.

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Seema M Thayil

Full Text Available Among HIV-infected individuals, co-infection with Mycobacterium tuberculosis is associated with faster progression to AIDS. We investigated the hypothesis that M. bovis BCG and M. tuberculosis (Mtb complex could enhance susceptibility of CD4+ cells to HIV infection. Peripheral blood mononuclear cells (PBMCs collected from healthy donors were stimulated with M. bovis BCG, M. tuberculosis CDC1551 and M. smegmatis MC(2155, and stimulated CD4+ cells were infected with R5-and X4-tropic single replication-competent pseudovirus. CD4+ cells stimulated with Mtb complex showed enhanced infection with R5- and X4-tropic HIV, compared to unstimulated cells or cells stimulated with M. smegmatis (p<0.01. Treatment with TLR2 siRNA reversed the increased susceptibility of CD4+ cells with R5- and X4-tropic virus induced by Mtb complex. These findings suggest that TB infection and/or BCG vaccination may be a risk factor for HIV acquisition.

Contrast enhanced ultrasound in the evaluation and percutaneous treatment of hepatic and renal tumors

International Nuclear Information System (INIS)

Meloni, Maria Franca; Smolock, Amanda; Cantisani, Vito; Bezzi, Mario; D'Ambrosio, Ferdinando; Proiti, Maria; Lee, Fred; Aiani, Luca; Calliada, Fabrizio; Ferraioli, Giovanna

2015-01-01

Highlights: • Image-guided percutaneous ablation techniques are increasingly being used for the treatment of malignant tumors of the liver and kidney when surgery is not indicated. • Percutaneous ablation relies on imaging at every step of the process in order to detect, guide, and confirm complete tumor coagulation. • CEUS is a real-time dynamic imaging technique that plays an important role in the management of patients treated with ablation for malignant tumors. • This review focuses on the role of CEUS in the evaluation of patients undergoing percutaneous treatments for hepatic and renal tumors. - Abstract: Image-guided percutaneous ablation techniques are increasingly being used for the treatment of malignant tumors of the liver and kidney. Contrast enhanced ultrasound (CEUS) is a real-time dynamic imaging technique that plays an important role in the pre-, intra-, and post-procedural management of these patients. This review will focus on the role of CEUS in the evaluation of patients undergoing treatment with percutaneous ablation for hepatic or renal tumors

Doxorubicin increases the effectiveness of Apo2L/TRAIL for tumor growth inhibition of prostate cancer xenografts

International Nuclear Information System (INIS)

El-Zawahry, Ahmed; McKillop, John; Voelkel-Johnson, Christina

2005-01-01

Prostate cancer is a significant health problem among American men. Treatment strategies for androgen-independent cancer are currently not available. Tumor necrosis factor-related apoptosis-inducing ligand (Apo2L/TRAIL) is a death receptor ligand that can induce apoptosis in a variety of cancer cell lines, including androgen-independent PC3 prostate carcinoma cells. In vitro, TRAIL-mediated apoptosis of prostate cancer cell lines can be enhanced by doxorubicin and correlates with the downregulation of the anti-apoptotic protein c-FLIP. This study evaluated the effects of doxorubicin on c-FLIP expression and tumor growth in combination with Apo2L/TRAIL in a xenograft model. In vitro cytotoxic effects of TRAIL were measured using a MTS-based viability assay. For in vivo studies, PC3 prostate carcinoma cells were grown subcutaneously in athymic nude mice and tumor growth was measured following treatment with doxorubicin and/or Apo2L/TRAIL. c-FLIP expression was determined by western blot analysis. Apoptosis in xenografts was detected using TUNEL. Statistical analysis was performed using the student t-test. In vitro experiments show that PC3 cells are partially susceptible to Apo2L/TRAIL and that susceptibility is enhanced by doxorubicin. In mice, doxorubicin did not significantly affect the growth of PC3 xenografts but reduced c-FLIP expression in tumors. Expression of c-FLIP in mouse heart was decreased only at the high doxorubicin concentration (8 mg/kg). Combination of doxorubicin with Apo2L/TRAIL resulted in more apoptotic cell death and tumor growth inhibition than Apo2L/TRAIL alone. Combination of doxorubicin and Apo2L/TRAIL is more effective in growth inhibition of PC3 xenografts in vivo than either agent alone and could present a novel treatment strategy against hormone-refractory prostate cancer. The intracellular mechanism by which doxorubicin enhances the effect of Apo2L/TRAIL on PC3 xenografts may be by reducing expression of c-FLIP

Study of arsenic trioxide-induced vascular shutdown and enhancement with radiation in solid tumor

International Nuclear Information System (INIS)

Monzen, Hajime; Griffin, R.J.; Williams, B.W.; Amamo, Morikazu; Ando, Satoshi; Hasegawa, Takeo

2004-01-01

Arsenic trioxide (ATO) has been reported to be an effective chemotherapeutic agent for acute promyelocytic leukemia (APL), and, recently, anti-tumor effect has been demonstrated in solid tumors. However, little is known about the mechanism of action of the ATO effect on solid tumor. We investigated the anti-vascular effect of ATO and the potential of combining ATO with radiation therapy. We studied the anti-vascular effect of ATO and radiosensitization of squamous cell carcinoma (SCC) VII murine tumors of C3H mice. The anti-vascular effect was examined using magnetic resonance imaging (MRI), and radiosensitivity was studied by clonogenic assay and tumor growth delay. Histopathological changes of the tumors after various treatments were also observed with hematoxylin and eosin (H and E) staining. Necrosis and blood flow changes in the central region of tumors in the hind limbs of the animals were observed on T2-weighted imaging after an intraperitoneal (i.p.) injection of 8 mg/kg of ATO alone. ATO exposure followed by radiation decreased the clonogenic survival of SCC VII cells compared with either treatment alone. Tumor growth delay after 10-20 Gy of radiation alone was increased slightly compared with control tumors, but the combination of ATO injection 2 hours before exposure to 20 Gy of radiation significantly prolonged tumor growth delay by almost 20 days. The results suggest that ATO and radiation can enhance the radiosensitivity of solid tumor. (author)

Enhanced tumor imaging with pokeweed mitogen

International Nuclear Information System (INIS)

Bitner, D.M.; Mann, P.L.; D'Souza, P.; Wenk, R.; Baughman, D.G.; Quesada, S.M.; Purvis, R.; Born, J.L.; Matwiyoff, N.A.; Eshima, D.

1993-01-01

Traditional tumor imaging with biotracer techniques relies solely on the target specificity of the biomolecule. We hypothesize that specific imaging is possible by altering the rate of tissue clearance of any given radiotracer. Pokeweed mitogen (PWM) as a biomodulator, represents a class of molecules which regulate cellular differentiation and cell-cell interactions and, as part of these mechanisms alter tissue clearance rates. Utilizing the B-16/C57BL/6 model, 7 days post-transplantation, 10 animals were imaged following an i.v. injection of 1-2 mCi 99m Tc-PWM in order to visualize the tumors and determine the optimal imaging kinetics. A specific tumor image is achieved between 120 and 240 min post-injection. In addition, tumor imaging studies using a non-tumor-specific biomolecule were conducted by injecting 19 animals i.v. with 1-2 mCi of 99m Tc-human serum albumin (HSA). Twelve of these animals were given 10 μg of PWM i.p. at various intervals prior to the 99m Tc-HAS administration. Imaging and biodistribution studies were performed at various intervals up to 2 h post- 99m Tc-HSA injection. A 32-59% increase in the tumor-to-muscle ratio was observed in the PWM-treated animals relative to the non-treated controls. To further investigate the PWM-induced tissue clearance alteration hypothesis, tissue clearance studies using 99m Tc-diethylenetriaminepentaacetic acid (DTPA) were conducted in non-tumor bearing ICR mice and the B-16/C57BL/6 tumor bearing animals. 99m Tc-DTPA normal tissue clearance rates were significantly increased in the PWM treated animals relative to the non-treated controls. (author)

Effects of ascorbic acid on carcinogenicity and acute toxicity of nickel subsulfide, and on tumor transplants growth in gulonolactone oxidase knock-out mice and wild-type C57BL mice

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Kasprzak, Kazimierz S. [Laboratory of Comparative Carcinogenesis, National Cancer Institute at Frederick, Frederick, MD 21702 (United States); Diwan, Bhalchandra A. [Basic Research Program, Science Applications International Corporation-Frederick, Inc., National Cancer Institute at Frederick, Frederick, MD 21702 (United States); Kaczmarek, Monika Z. [Laboratory of Comparative Carcinogenesis, National Cancer Institute at Frederick, Frederick, MD 21702 (United States); Logsdon, Daniel L. [Laboratory Animal Sciences Program, Science Applications International Corporation-Frederick, Inc., National Cancer Institute at Frederick, Frederick, MD 21702 (United States); Fivash, Mathew J. [Data Management Services, National Cancer Institute at Frederick, Frederick, MD 21702 (United States); Salnikow, Konstantin, E-mail: salnikok@mail.nih.gov [Laboratory of Comparative Carcinogenesis, National Cancer Institute at Frederick, Frederick, MD 21702 (United States)

2011-11-15

The aim of this study was to test a hypothesis that ascorbate depletion could enhance carcinogenicity and acute toxicity of nickel. Homozygous L-gulono- < gamma > -lactone oxidase gene knock-out mice (Gulo-/- mice) unable to produce ascorbate and wild-type C57BL mice (WT mice) were injected intramuscularly with carcinogenic nickel subsulfide (Ni{sub 3}S{sub 2}), and observed for the development of injection site tumors for 57 weeks. Small pieces of one of the induced tumors were transplanted subcutaneously into separate groups of Gulo-/- and WT mice and the growth of these tumors was measured for up to 3 months. The two strains of mice differed significantly with regard to (1) Ni{sub 3}S{sub 2} carcinogenesis: Gulo-/- mice were 40% more susceptible than WT mice; and (2) transplanted tumors development: Gulo-/- mice were more receptive to tumor growth than WT mice, but only in terms of a much shorter tumor latency; later in the exponential phase of growth, the growth rates were the same. And, with adequate ascorbate supplementation, the two strains were equally susceptible to acute toxicity of Ni{sub 3}S{sub 2}. Statistically significant effects of dietary ascorbate dosing levels were the following: (1) reduction in ascorbate supplementation increased acute toxicity of Ni{sub 3}S{sub 2} in Gulo-/- mice; (2) ascorbate supplementation extended the latency of transplanted tumors in WT mice. In conclusion, the lack of endogenous ascorbate synthesis makes Gulo-/- mice more susceptible to Ni{sub 3}S{sub 2} carcinogenesis. Dietary ascorbate tends to attenuate acute toxicity of Ni{sub 3}S{sub 2} and to extend the latency of transplanted tumors. The latter effects may be of practical importance to humans and thus deserve further studies. -- Highlights: Black-Right-Pointing-Pointer Ascorbate depletion enhances carcinogenicity and acute toxicity of nickel. Black-Right-Pointing-Pointer Gulo-/- mice unable to synthesize ascorbate were used in this study. Black

Effects of ascorbic acid on carcinogenicity and acute toxicity of nickel subsulfide, and on tumor transplants growth in gulonolactone oxidase knock-out mice and wild-type C57BL mice

International Nuclear Information System (INIS)

Kasprzak, Kazimierz S.; Diwan, Bhalchandra A.; Kaczmarek, Monika Z.; Logsdon, Daniel L.; Fivash, Mathew J.; Salnikow, Konstantin

2011-01-01

The aim of this study was to test a hypothesis that ascorbate depletion could enhance carcinogenicity and acute toxicity of nickel. Homozygous L-gulono- -lactone oxidase gene knock-out mice (Gulo−/− mice) unable to produce ascorbate and wild-type C57BL mice (WT mice) were injected intramuscularly with carcinogenic nickel subsulfide (Ni 3 S 2 ), and observed for the development of injection site tumors for 57 weeks. Small pieces of one of the induced tumors were transplanted subcutaneously into separate groups of Gulo−/− and WT mice and the growth of these tumors was measured for up to 3 months. The two strains of mice differed significantly with regard to (1) Ni 3 S 2 carcinogenesis: Gulo−/− mice were 40% more susceptible than WT mice; and (2) transplanted tumors development: Gulo−/− mice were more receptive to tumor growth than WT mice, but only in terms of a much shorter tumor latency; later in the exponential phase of growth, the growth rates were the same. And, with adequate ascorbate supplementation, the two strains were equally susceptible to acute toxicity of Ni 3 S 2 . Statistically significant effects of dietary ascorbate dosing levels were the following: (1) reduction in ascorbate supplementation increased acute toxicity of Ni 3 S 2 in Gulo−/− mice; (2) ascorbate supplementation extended the latency of transplanted tumors in WT mice. In conclusion, the lack of endogenous ascorbate synthesis makes Gulo−/− mice more susceptible to Ni 3 S 2 carcinogenesis. Dietary ascorbate tends to attenuate acute toxicity of Ni 3 S 2 and to extend the latency of transplanted tumors. The latter effects may be of practical importance to humans and thus deserve further studies. -- Highlights: ► Ascorbate depletion enhances carcinogenicity and acute toxicity of nickel. ► Gulo−/− mice unable to synthesize ascorbate were used in this study. ► The reduction in ascorbate levels in Gulo−/− mice increased acute toxicity induced by Ni 3 S 2 . �

Vulnerability of cultured canine lung tumor cells to NK cell-mediated cytolysis

International Nuclear Information System (INIS)

Haley, P.J.; Kohr, J.M.; Kelly, G.; Muggenburg, B.A.; Guilmette, B.A.

1988-01-01

Five cell lines, designated as canine lung epithelial cell (CLEP), derived from radiation induced canine lung tumors and canine thyroid adeno-carcinoma (CTAC) cells were compared for their susceptibility to NK cell-mediated cytolysis using peripheral blood lymphocytes from normal, healthy Beagle dogs as effector cells. Effector cells and chromium 51 radiolabeled target cells were incubated for 16 h at ratios of 12.5:1, 25:1, 50:1, and 100:1. Increasing cytolysis was observed for all cell lines as the effector-to-target-cell ratios increased from 12.5:1 to 100:1. The percent cytotoxicity was significantly less for all lung tumor cell lines as compared to CTAC at the 100:1 ratio. One lung tumor cell line, CLEP-9, had 85% of the lytic vulnerability of the CTAC cell line and significantly greater susceptibility to NK cell-mediated lysis than all of the other lung tumor cell lines. Susceptibility to NK cell cytolysis did not correlate with in vivo malignant behavior of the original tumor. These data suggest that cultured canine lung tumor cells are susceptible to NK cell cytolytic activity in vitro and that at least one of these cell lines (CLEP-9) is a candidate for substitution of the standard canine NK cell target, CTAC, in NK cell assays. The use of lung tumor cells in NK cell assays may provide greater insight into the control of lung tumors by immune mechanisms. (author)

Diagnosis of portal vein thrombosis discontinued with liver tumors in patients with liver cirrhosis and tumors by contrast-enhanced US: A pilot study

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Song Zezhou; Huang Min [Department of Ultrasound, First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, Zhejiang Province (China); Jiang Tianan, E-mail: tiananjiang@hzcnc.co [Department of Ultrasound, First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, Zhejiang Province (China); Zhao Qiyu [Department of Hepatobiliary Pancreatic Surgery, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou (China); Yao Lei; Mou Yun; Zhao Junkang; Ao Jianyang [Department of Ultrasound, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, Zhejiang Province (China); Chen Fen [Department of Hepatobiliary Pancreatic Surgery, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou (China); Chen Yan [Department of Ultrasound, First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, Zhejiang Province (China)

2010-08-15

Aims: We assessed the role of contrast-enhanced ultrasound (CEUS) in the differential diagnosis between benign and malignant portal vein thrombosis (PVT) in patients who had liver tumors. Methods: Seventeen consecutive patients who had cirrhosis, liver tumors, and PVT were prospectively studied with CEUS. CEUS was performed at low mechanical index after intravenous administration of a second-generation contrast agent (SonoVue, Bracco, Milan, Italy). Presence or absence of thrombus enhancement on CEUS were considered diagnostic for malignant or benign PVT. Five patients also underwent percutaneous portal vein fine-needle biopsy under US guidance. All patients were followed-up. Shrinkage of the thrombus and/or recanalization of the vessels on CDUS during follow-up were considered definitive evidence of the benign nature of the thrombosis, whereas the enlargement of the thrombus, disruption of the vessel wall, and parenchymal infiltration over follow-up were considered consistent with malignancy. Results: Follow-up showed signs of malignant thrombosis in 14 of 17 patients. CEUS showed early arterial enhancement of the PVT in 14 patients of 14 malignant PVT, 1 patient of 3 benign PVT and the absence of thrombus enhancement in 2 patients of 3 benign PVT. FNB confirmed the results for malignant PVT in four of five patients, for benign granulomatous inflammation PVT in one of five patients in which CEUS showed early arterial enhancement of the PVT. The sensitivity, specificity and accuracy is 100%, 66.7% and 93.3% at diagnosis of malignant PVT using CEUS. In one patient with intrahepatic bile duct stone, CEUS were positive for malignant PVT, whereas FNB was negative (benign granulomatous inflammation PVT); follow-up examination confirmed benign PVT. Conclusion: CEUS seems to be the pretty sensitive and specific test for diagnosing malignant portal vein thrombosis in patients with cirrhosis and tumors.

Glioblastomas vs. lymphomas. More diagnostic certainty by using susceptibility-weighted imaging (SWI)

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Peters, S.; Knoess, N.; Wodarg, F.; Cnyrim, C.; Jansen, O. [Universitaetsklinikum Schleswig-Holstein, Kiel (Germany). Inst. fuer Neuroradiologie

2012-08-15

Purpose: It can be difficult to differentiate glioblastomas from lymphomas using only standard MR images. There are references suggesting that it might be possible to differentiate these tumors using susceptibility-weighted imaging (SWI). The purpose of this study is to prove the diagnostic benefit using susceptibility-weighted images. Material and Methods: Three neuroradiologists tried to differentiate 4 histologically verified lymphomas from 11 glioblastomas in retrospect. They first viewed the conventional MR images and declared a diagnosis with a grade of certainty. Afterwards they additionally reviewed the susceptibility-weighted images. Results: Glioblastomas have a clearly higher grade of susceptibility signals than lymphomas. By additionally using susceptibility-weighted images, the radiologists determined the correct diagnosis in 82.2 % of the cases. Without susceptibility-weighted images, the diagnosis was correct in 75.5 % of the cases. The subjective gain of certainty was 16.5 %. If there were no intratumoral susceptibility signals (ITSS) (grade 1), the sensitivity for diagnosing a lymphoma was 70 % and the specificity was 100 %. The sensitivity for diagnosing a glioblastoma was 90.5 % and the specificity was 100 % if there was a high rate of intratumoral susceptibility signals (grade 3). Conclusion: Susceptibility-weighted images are an additional tool in clinical practice for determining the correct diagnosis. The differentiation between glioblastomas and lymphomas and the certainty of the determined diagnosis are better. Therefore, we recommend adding susceptibility-weighted imaging to the clinical MR tumor protocol. (orig.)

Glioblastomas vs. lymphomas: more diagnostic certainty by using susceptibility-weighted imaging (SWI).

Science.gov (United States)

Peters, S; Knöß, N; Wodarg, F; Cnyrim, C; Jansen, O

2012-08-01

It can be difficult to differentiate glioblastomas from lymphomas using only standard MR images. There are references suggesting that it might be possible to differentiate these tumors using susceptibility-weighted imaging (SWI). The purpose of this study is to prove the diagnostic benefit using susceptibility-weighted images. Three neuroradiologists tried to differentiate 4 histologically verified lymphomas from 11 glioblastomas in retrospect. They first viewed the conventional MR images and declared a diagnosis with a grade of certainty. Afterwards they additionally reviewed the susceptibility-weighted images. Glioblastomas have a clearly higher grade of susceptibility signals than lymphomas. By additionally using susceptibility-weighted images, the radiologists determined the correct diagnosis in 82.2 % of the cases. Without susceptibility-weighted images, the diagnosis was correct in 75.5 % of the cases. The subjective gain of certainty was 16.5 %. If there were no intratumoral susceptibility signals (ITSS) (grade 1), the sensitivity for diagnosing a lymphoma was 70 % and the specificity was 100 %. The sensitivity for diagnosing a glioblastoma was 90.5 % and the specificity was 100 % if there was a high rate of intratumoral susceptibility signals (grade 3). Susceptibility-weighted images are an additional tool in clinical practice for determining the correct diagnosis. The differentiation between glioblastomas and lymphomas and the certainty of the determined diagnosis are better. Therefore, we recommend adding susceptibility-weighted imaging to the clinical MR tumor protocol. © Georg Thieme Verlag KG Stuttgart · New York.

Glioblastomas vs. lymphomas. More diagnostic certainty by using susceptibility-weighted imaging (SWI)

International Nuclear Information System (INIS)

Peters, S.; Knoess, N.; Wodarg, F.; Cnyrim, C.; Jansen, O.

2012-01-01

Purpose: It can be difficult to differentiate glioblastomas from lymphomas using only standard MR images. There are references suggesting that it might be possible to differentiate these tumors using susceptibility-weighted imaging (SWI). The purpose of this study is to prove the diagnostic benefit using susceptibility-weighted images. Material and Methods: Three neuroradiologists tried to differentiate 4 histologically verified lymphomas from 11 glioblastomas in retrospect. They first viewed the conventional MR images and declared a diagnosis with a grade of certainty. Afterwards they additionally reviewed the susceptibility-weighted images. Results: Glioblastomas have a clearly higher grade of susceptibility signals than lymphomas. By additionally using susceptibility-weighted images, the radiologists determined the correct diagnosis in 82.2 % of the cases. Without susceptibility-weighted images, the diagnosis was correct in 75.5 % of the cases. The subjective gain of certainty was 16.5 %. If there were no intratumoral susceptibility signals (ITSS) (grade 1), the sensitivity for diagnosing a lymphoma was 70 % and the specificity was 100 %. The sensitivity for diagnosing a glioblastoma was 90.5 % and the specificity was 100 % if there was a high rate of intratumoral susceptibility signals (grade 3). Conclusion: Susceptibility-weighted images are an additional tool in clinical practice for determining the correct diagnosis. The differentiation between glioblastomas and lymphomas and the certainty of the determined diagnosis are better. Therefore, we recommend adding susceptibility-weighted imaging to the clinical MR tumor protocol. (orig.)

Enhanced Delivery of Gold Nanoparticles with Therapeutic Potential for Targeting Human Brain Tumors

Science.gov (United States)

Etame, Arnold B.

The blood brain barrier (BBB) remains a major challenge to the advancement and application of systemic anti-cancer therapeutics into the central nervous system. The structural and physiological delivery constraints of the BBB significantly limit the effectiveness of conventional chemotherapy, thereby making systemic administration a non-viable option for the vast majority of chemotherapy agents. Furthermore, the lack of specificity of conventional systemic chemotherapy when applied towards malignant brain tumors remains a major shortcoming. Hence novel therapeutic strategies that focus both on targeted and enhanced delivery across the BBB are warranted. In recent years nanoparticles (NPs) have emerged as attractive vehicles for efficient delivery of targeted anti-cancer therapeutics. In particular, gold nanoparticles (AuNPs) have gained prominence in several targeting applications involving systemic cancers. Their enhanced permeation and retention within permissive tumor microvasculature provide a selective advantage for targeting. Malignant brain tumors also exhibit transport-permissive microvasculature secondary to blood brain barrier disruption. Hence AuNPs may have potential relevance for brain tumor targeting. However, the permeation of AuNPs across the BBB has not been well characterized, and hence is a potential limitation for successful application of AuNP-based therapeutics within the central nervous system (CNS). In this dissertation, we designed and characterized AuNPs and assessed the role of polyethylene glycol (PEG) on the physical and biological properties of AuNPs. We established a size-dependent permeation profile with respect to core size as well as PEG length when AuNPs were assessed through a transport-permissive in-vitro BBB. This study was the first of its kind to systematically examine the influence of design on permeation of AuNPs through transport-permissive BBB. Given the significant delivery limitations through the non

Enhancement of tumor radioresponse by wortmannin in C3H/HeJ hepatocarcinoma

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Kim, Wonwoo; Seong, Jinsil; An, Jung-Hee; Oh, Hae-Jin [Yonsei Univ., Seoul (Korea, Republic of)

2007-05-15

The objective of this study was to explore whether a specific inhibitor of phosphatidylinositol 3-kinase (PI3K), wortmannin, could potentiate the antitumor effect of radiation in vivo, particularly on radioresistant murine tumors. C3H/HeJ mice bearing syngeneic hepatocarcinoma (HCa-I) were treated with 25 Gy radiation, wortmannin, or both. Wortmannin was administered intraperitoneally (1 mg/kg) once daily for 14 days. Tumor response to treatment was determined by a tumor growth delay assay. Possible mechanisms of action were explored by examining the level of apoptosis and regulating molecules. The expression of regulating molecules was analyzed by Western blot for p53 and p21{sup WAF1/CIP1}, and immunohistochemical staining for p21{sup WAF1/CIP1}, CD31 and vascular endothelial growth factor (VEGF). In the tumor growth delay assay, wortmannin increased the effect of tumor radioresponse with an enhancement factor (EF) of 2.00. The level of apoptosis achieved by the combined treatments was shown to be no more than an additive effect; peak apoptotic index was 11% in radiation alone, 13% in wortmannin alone, and 19% in the combination group. Markedly increased areas of necrosis at 24 h in the combination group were noted. Western blotting showed upregulation of p21{sup WAF1/CIP1} in the combination treatment group, which correlated with low levels of VEGF. Microvascular density was evidently also reduced, based on low expression of CD31. In murine hepatocarcinoma, the antitumor effect of radiation was potentiated by wortmannin. The mechanism seems to involve not only the increase of induced apoptosis but also enhanced vascular injury. Wortmannin, in combination with radiation therapy, may have potential benefits in cancer treatment. (author)

Enhancement of tumor radioresponse by wortmannin in C3H/HeJ hepatocarcinoma

International Nuclear Information System (INIS)

Kim, Wonwoo; Seong, Jinsil; An, Jung-Hee; Oh, Hae-Jin

2007-01-01

The objective of this study was to explore whether a specific inhibitor of phosphatidylinositol 3-kinase (PI3K), wortmannin, could potentiate the antitumor effect of radiation in vivo, particularly on radioresistant murine tumors. C3H/HeJ mice bearing syngeneic hepatocarcinoma (HCa-I) were treated with 25 Gy radiation, wortmannin, or both. Wortmannin was administered intraperitoneally (1 mg/kg) once daily for 14 days. Tumor response to treatment was determined by a tumor growth delay assay. Possible mechanisms of action were explored by examining the level of apoptosis and regulating molecules. The expression of regulating molecules was analyzed by Western blot for p53 and p21 WAF1/CIP1 , and immunohistochemical staining for p21 WAF1/CIP1 , CD31 and vascular endothelial growth factor (VEGF). In the tumor growth delay assay, wortmannin increased the effect of tumor radioresponse with an enhancement factor (EF) of 2.00. The level of apoptosis achieved by the combined treatments was shown to be no more than an additive effect; peak apoptotic index was 11% in radiation alone, 13% in wortmannin alone, and 19% in the combination group. Markedly increased areas of necrosis at 24 h in the combination group were noted. Western blotting showed upregulation of p21 WAF1/CIP1 in the combination treatment group, which correlated with low levels of VEGF. Microvascular density was evidently also reduced, based on low expression of CD31. In murine hepatocarcinoma, the antitumor effect of radiation was potentiated by wortmannin. The mechanism seems to involve not only the increase of induced apoptosis but also enhanced vascular injury. Wortmannin, in combination with radiation therapy, may have potential benefits in cancer treatment. (author)

Poly (I:C) enhances the anti-tumor activity of canine parvovirus NS1 protein by inducing a potent anti-tumor immune response.

Science.gov (United States)

Gupta, Shishir Kumar; Yadav, Pavan Kumar; Tiwari, A K; Gandham, Ravi Kumar; Sahoo, A P

2016-09-01

The canine parvovirus NS1 (CPV2.NS1) protein selectively induces apoptosis in the malignant cells. However, for an effective in vivo tumor treatment strategy, an oncolytic agent also needs to induce a potent anti-tumor immune response. In the present study, we used poly (I:C), a TLR3 ligand, as an adjuvant along with CPV2.NS1 to find out if the combination can enhance the oncolytic activity by inducing a potent anti-tumor immune response. The 4T1 mammary carcinoma cells were used to induce mammary tumor in Balb/c mice. The results suggested that poly (I:C), when given along with CPV2.NS1, not only significantly reduced the tumor growth but also augmented the immune response against tumor antigen(s) as indicated by the increase in blood CD4+ and CD8+ counts and infiltration of immune cells in the tumor tissue. Further, blood serum analysis of the cytokines revealed that Th1 cytokines (IFN-γ and IL-2) were significantly upregulated in the treatment group indicating activation of cell-mediated immune response. The present study reports the efficacy of CPV2.NS1 along with poly (I:C) not only in inhibiting the mammary tumor growth but also in generating an active anti-tumor immune response without any visible toxicity. The results of our study may help in developing CPV2.NS1 and poly (I: C) combination as a cancer therapeutic regime to treat various malignancies.

Differentiation between benign and malignant colon tumors using fast dynamic gadolinium-enhanced MR colonography; a feasibility study

DEFF Research Database (Denmark)

Achiam, M P; Andersen, L P H; Klein, M

2010-01-01

Colorectal cancer will present itself as a bowel obstruction in 16-23% of all cases. However, not all obstructing tumors are malignant and the differentiation between a benign and a malignant tumor can be difficult. The purpose of our study was to determine whether fast dynamic gadolinium-enhance...

Assessment of Tumor Radioresponsiveness and Metastatic Potential by Dynamic Contrast-Enhanced Magnetic Resonance Imaging

International Nuclear Information System (INIS)

Ovrebo, Kirsti Marie; Gulliksrud, Kristine; Mathiesen, Berit; Rofstad, Einar K.

2011-01-01

Purpose: It has been suggested that gadolinium diethylene-triamine penta-acetic acid (Gd-DTPA)-based dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) may provide clinically useful biomarkers for personalized cancer treatment. In this preclinical study, we investigated the potential of DCE-MRI as a noninvasive method for assessing the radioresponsiveness and metastatic potential of tumors. Methods and Materials: R-18 melanoma xenografts growing in BALB/c nu/nu mice were used as experimental tumor models. Fifty tumors were subjected to DCE-MRI, and parametric images of K trans (the volume transfer constant of Gd-DTPA) and v e (the fractional distribution volume of Gd-DTPA) were produced by pharmacokinetic analysis of the DCE-MRI series. The tumors were irradiated after the DCE-MRI, either with a single dose of 10 Gy for detection of radiobiological hypoxia (30 tumors) or with five fractions of 4 Gy in 48 h for assessment of radioresponsiveness (20 tumors). The host mice were then euthanized and examined for lymph node metastases, and the primary tumors were resected for measurement of cell survival in vitro. Results: Tumors with hypoxic cells showed significantly lower K trans values than tumors without significant hypoxia (p trans decreased with increasing cell surviving fraction for tumors given fractionated radiation treatment (p trans values than tumors in metastasis-negative mice (p e and tumor hypoxia, radioresponsiveness, or metastatic potential could not be detected. Conclusions: R-18 tumors with low K trans values are likely to be resistant to radiation treatment and have a high probability of developing lymph node metastases. The general validity of these observations should be investigated further by studying preclinical tumor models with biological properties different from those of the R-18 tumors.

Contrast-enhanced computed tomography of the primary tumor in muscle invasive carcinoma of the urinary bladder

International Nuclear Information System (INIS)

Sager, E.M.

1991-01-01

Patients with muscle invasive carcinoma of the urinary bladder were examined with contrast-enhanced CT of the primary tumor. A specially designed technique was developed to increase the diagnostic potential of CT. The most important points about the technique were controlled filling of the bladder, the use of thin slices, series of scans before and after intravenous injection of contrast medium, and long scanning times in the precontrast series. The absorbed dose to the patient resulting from the new technique was found to be within the range of the dose from urography or barium enema. This dose was considered to be acceptable given the diagnostic gain of the procedure. Features of irradiated bladder tumors were analysed to find which parameter correlated with persistent malignancy. High contrast enhancement of a tumor relative to the bladder wall was found to be the best indicator of a malignant tumour after irradiation. 127 refs

Contrast-enhanced MR imaging of hematogenous metastases of the VX2 tumor to the rabbit eye

International Nuclear Information System (INIS)

Frank, J.A.; Girton, M.; Dwyer, A.J.

1986-01-01

The authors have developed a reproducible model of hematogenous spread of malignancy to the eye of the rabbit. VX2 tumor cells (10/sup 6/ cells) were infused into the internal carotid artery of 15 New Zealand white rabbits weighting 2.5-3.5 kg. Ocular metastases developed in more than 90% of animals within 3-11 days. MR images were obtained 6-12 days after tumor inoculation (Picker, 0.5 T, saddle-shaped surface coil, 15-cm FOV, 5-mm section thickness). Tl-weighted SE550/40 images obtained after administration of Gd-DPTA (0.1) mmol/kg, given intravenously) demonstrated enhancement of aqueous humor due to disruption of the blood-ocular barrier and delineated tumor within the choroid. Metastases were confirmed at autopsy. The findings suggest the potential use of gadolinium-enhanced MR imaging for detecting ocular metastases and monitoring their growth

Identification of differentially expressed genes associated with the enhancement of X-ray susceptibility by RITA in a hypopharyngeal squamous cell carcinoma cell line (FaDu).

Science.gov (United States)

Luan, Jinwei; Li, Xianglan; Guo, Rutao; Liu, Shanshan; Luo, Hongyu; You, Qingshan

2016-06-01

Next generation sequencing and bio-informatic analyses were conducted to investigate the mechanism of reactivation of p53 and induction of tumor cell apoptosis (RITA)-enhancing X-ray susceptibility in FaDu cells. The cDNA was isolated from FaDu cells treated with 0 X-ray, 8 Gy X-ray, or 8 Gy X-ray + RITA. Then, cDNA libraries were created and sequenced using next generation sequencing, and each assay was repeated twice. Subsequently, differentially expressed genes (DEGs) were identified using Cuffdiff in Cufflinks and their functions were predicted by pathway enrichment analyses. Genes that were constantly up- or down-regulated in 8 Gy X-ray-treated FaDu cells and 8 Gy X-ray + RITA-treated FaDu cells were obtained as RITA genes. Afterward, the protein-protein interaction (PPI) relationships were obtained from the STRING database and a PPI network was constructed using Cytoscape. Furthermore, ClueGO was used for pathway enrichment analysis of genes in the PPI network. Total 2,040 and 297 DEGs were identified in FaDu cells treated with 8 Gy X-ray or 8 Gy X-ray + RITA, respectively. PARP3 and NEIL1 were enriched in base excision repair, and CDK1 was enriched in p53 signaling pathway. RFC2 and EZH2 were identified as RITA genes. In the PPI network, many interaction relationships were identified (e.g., RFC2-CDK1, EZH2-CDK1 and PARP3-EZH2). ClueGO analysis showed that RFC2 and EZH2 were related to cell cycle. RFC2, EZH2, CDK1, PARP3 and NEIL1 may be associated, and together enhance the susceptibility of FaDu cells treated with RITA to the deleterious effects of X-ray.

Identification of differentially expressed genes associated with the enhancement of X-ray susceptibility by RITA in a hypopharyngeal squamous cell carcinoma cell line (FaDu)

International Nuclear Information System (INIS)

Luan, Jinwei; Li, Xianglan; Guo, Rutao; Liu, Shanshan; Luo, Hongyu; You, Qingshan

2016-01-01

Next generation sequencing and bio-informatic analyses were conducted to investigate the mechanism of reactivation of p53 and induction of tumor cell apoptosis (RITA)-enhancing X-ray susceptibility in FaDu cells. The cDNA was isolated from FaDu cells treated with 0 X-ray, 8 Gy X-ray, or 8 Gy X-ray + RITA. Then, cDNA libraries were created and sequenced using next generation sequencing, and each assay was repeated twice. Subsequently, differentially expressed genes (DEGs) were identified using Cuffdiff in Cufflinks and their functions were predicted by pathway enrichment analyses. Genes that were constantly up- or down-regulated in 8 Gy X-ray-treated FaDu cells and 8 Gy X-ray + RITA-treated FaDu cells were obtained as RITA genes. Afterward, the protein-protein interaction (PPI) relationships were obtained from the STRING database and a PPI network was constructed using Cytoscape. Furthermore, ClueGO was used for pathway enrichment analysis of genes in the PPI network. Total 2,040 and 297 DEGs were identified in FaDu cells treated with 8 Gy X-ray or 8 Gy X-ray + RITA, respectively. PARP3 and NEIL1 were enriched in base excision repair, and CDK1 was enriched in p53 signaling pathway. RFC2 and EZH2 were identified as RITA genes. In the PPI network, many interaction relationships were identified (e.g., RFC2-CDK1, EZH2-CDK1 and PARP3-EZH2). ClueGO analysis showed that RFC2 and EZH2 were related to cell cycle. RFC2, EZH2, CDK1, PARP3 and NEIL1 may be associated, and together enhance the susceptibility of FaDu cells treated with RITA to the deleterious effects of X-ray

Clinical oxygen enhancement ratio of tumors in carbon ion radiotherapy: the influence of local oxygenation changes

DEFF Research Database (Denmark)

Antonovic, Laura; Lindblom, Emely; Dasu, Alexandru

2014-01-01

, using the repairable–conditionally repairable (RCR) damage model with parameters for human salivary gland tumor cells. The clinical oxygen enhancement ratio (OER) was defined as the ratio of doses required for a tumor control probability of 50% for hypoxic and well-oxygenated tumors. The resulting OER...... was well above unity for all fractionations. For the hypoxic tumor, the tumor control probability was considerably higher if LOCs were assumed, rather than static oxygenation. The beneficial effect of LOCs increased with the number of fractions. However, for very low fraction doses, the improvement related...... to LOCs did not compensate for the increase in total dose required for tumor control. In conclusion, our results suggest that hypoxia can influence the outcome of carbon ion radiotherapy because of the non-negligible oxygen effect at the low LETs in the SOBP. However, if LOCs occur, a relatively high...

Co-delivery of paclitaxel and cetuximab by nanodiamond enhances mitotic catastrophe and tumor inhibition.

Science.gov (United States)

Lin, Yu-Wei; Raj, Emmanuel Naveen; Liao, Wei-Siang; Lin, Johnson; Liu, Kuang-Kai; Chen, Ting-Hua; Cheng, Hsiao-Chun; Wang, Chi-Ching; Li, Lily Yi; Chen, Chinpiao; Chao, Jui-I

2017-08-29

The poor intracellular uptake and non-specific binding of anticancer drugs into cancer cells are the bottlenecks in cancer therapy. Nanocarrier platforms provide the opportunities to improve the drug efficacy. Here we show a carbon-based nanomaterial nanodiamond (ND) that carried paclitaxel (PTX), a microtubule inhibitor, and cetuximab (Cet), a specific monoclonal antibody against epidermal growth factor receptor (EGFR), inducing mitotic catastrophe and tumor inhibition in human colorectal cancer (CRC). ND-PTX blocked the mitotic progression, chromosomal separation, and induced apoptosis in the CRC cells; however, NDs did not induce these effects. Conjugation of ND-PTX with Cet (ND-PTX-Cet) was specifically binding to the EGFR-positive CRC cells and enhanced the mitotic catastrophe and apoptosis induction. Besides, ND-PTX-Cet markedly decreased tumor size in the xenograft EGFR-expressed human CRC tumors of nude mice. Moreover, ND-PTX-Cet induced the mitotic marker protein phospho-histone 3 (Ser10) and apoptotic protein active-caspase 3 for mitotic catastrophe and apoptosis. Taken together, this study demonstrated that the co-delivery of PTX and Cet by ND enhanced the effects of mitotic catastrophe and apoptosis in vitro and in vivo, which may be applied in the human CRC therapy.

IL-15 protects NKT cells from inhibition by tumor-associated macrophages and enhances antimetastatic activity

Science.gov (United States)

Liu, Daofeng; Song, Liping; Wei, Jie; Courtney, Amy N.; Gao, Xiuhua; Marinova, Ekaterina; Guo, Linjie; Heczey, Andras; Asgharzadeh, Shahab; Kim, Eugene; Dotti, Gianpietro; Metelitsa, Leonid S.

2012-01-01

Vα24-invariant NKT cells inhibit tumor growth by targeting tumor-associated macrophages (TAMs). Tumor progression therefore requires that TAMs evade NKT cell activity through yet-unknown mechanisms. Here we report that a subset of cells in neuroblastoma (NB) cell lines and primary tumors expresses membrane-bound TNF-α (mbTNF-α). These proinflammatory tumor cells induced production of the chemokine CCL20 from TAMs via activation of the NF-κB signaling pathway, an effect that was amplified in hypoxia. Flow cytometry analyses of human primary NB tumors revealed selective accumulation of CCL20 in TAMs. Neutralization of the chemokine inhibited in vitro migration of NKT cells toward tumor-conditioned hypoxic monocytes and localization of NKT cells to NB grafts in mice. We also found that hypoxia impaired NKT cell viability and function. Thus, CCL20-producing TAMs served as a hypoxic trap for tumor-infiltrating NKT cells. IL-15 protected antigen-activated NKT cells from hypoxia, and transgenic expression of IL-15 in adoptively transferred NKT cells dramatically enhanced their antimetastatic activity in mice. Thus, tumor-induced chemokine production in hypoxic TAMs and consequent chemoattraction and inhibition of NKT cells represents a mechanism of immune escape that can be reversed by adoptive immunotherapy with IL-15–transduced NKT cells. PMID:22565311

IL-15 protects NKT cells from inhibition by tumor-associated macrophages and enhances antimetastatic activity.

Science.gov (United States)

Liu, Daofeng; Song, Liping; Wei, Jie; Courtney, Amy N; Gao, Xiuhua; Marinova, Ekaterina; Guo, Linjie; Heczey, Andras; Asgharzadeh, Shahab; Kim, Eugene; Dotti, Gianpietro; Metelitsa, Leonid S

2012-06-01

Vα24-invariant NKT cells inhibit tumor growth by targeting tumor-associated macrophages (TAMs). Tumor progression therefore requires that TAMs evade NKT cell activity through yet-unknown mechanisms. Here we report that a subset of cells in neuroblastoma (NB) cell lines and primary tumors expresses membrane-bound TNF-α (mbTNF-α). These proinflammatory tumor cells induced production of the chemokine CCL20 from TAMs via activation of the NF-κB signaling pathway, an effect that was amplified in hypoxia. Flow cytometry analyses of human primary NB tumors revealed selective accumulation of CCL20 in TAMs. Neutralization of the chemokine inhibited in vitro migration of NKT cells toward tumor-conditioned hypoxic monocytes and localization of NKT cells to NB grafts in mice. We also found that hypoxia impaired NKT cell viability and function. Thus, CCL20-producing TAMs served as a hypoxic trap for tumor-infiltrating NKT cells. IL-15 protected antigen-activated NKT cells from hypoxia, and transgenic expression of IL-15 in adoptively transferred NKT cells dramatically enhanced their antimetastatic activity in mice. Thus, tumor-induced chemokine production in hypoxic TAMs and consequent chemoattraction and inhibition of NKT cells represents a mechanism of immune escape that can be reversed by adoptive immunotherapy with IL-15-transduced NKT cells.

Differentiation between benign and malignant colon tumors using fast dynamic gadolinium-enhanced MR colonography; a feasibility study

International Nuclear Information System (INIS)

Achiam, M.P.; Andersen, L.P.H.; Klein, M.; Logager, V.; Chabanova, E.; Thomsen, H.S.; Rosenberg, J.

2010-01-01

Background: Colorectal cancer will present itself as a bowel obstruction in 16-23% of all cases. However, not all obstructing tumors are malignant and the differentiation between a benign and a malignant tumor can be difficult. The purpose of our study was to determine whether fast dynamic gadolinium-enhanced MR imaging combined with MR colonography could be used to differentiate a benign from a malignant obstructing colon tumor. Methods: Patients with benign colon tumor stenosis, based on diverticulitis, were asked to participate in the study. The same number of patients with verified colorectal cancer was included. Both groups had to be scheduled for surgery to be included. Two blinded observers analyzed the tumors on MR by placing a region of interest in the tumor and a series of parameters were evaluated, e.g. wash-in, wash-out and time-to-peak. Results: 14 patients were included. The wash-in and wash-out rates were significantly different between the benign and malignant tumors, and a clear distinction between benign and malignant disease was therefore possible by looking only at the MR data. Furthermore, MR colography evaluating the rest of the colon past the stenosis was possible with all patients. Conclusion: The results showed the feasibility of using fast dynamic gadolinium-enhanced MR imaging to differentiate between benign and malignant colonic tumors. With a high intra-class correlation and significant differences found on independent segments of the tumor, the method appears to be reproducible. Furthermore, the potential is big in performing a full preoperative colon evaluation even in patients with obstructing cancer. Trial number: (NCT00114829).

Differentiation between benign and malignant colon tumors using fast dynamic gadolinium-enhanced MR colonography; a feasibility study

Energy Technology Data Exchange (ETDEWEB)

Achiam, M.P., E-mail: achiam1@dadlnet.d [Department of Diagnostic Radiology, Copenhagen University Hospital Herlev, Herlev Ringvej, DK-2730 Herlev (Denmark); Department of Surgical Gastroenterology D, Copenhagen University Hospital Herlev, Herlev Ringvej, DK-2730 Herlev (Denmark); Department of Diagnostic Sciences, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3C, DK-2200 Copenhagen (Denmark); Andersen, L.P.H.; Klein, M. [Department of Surgical Gastroenterology D, Copenhagen University Hospital Herlev, Herlev Ringvej, DK-2730 Herlev (Denmark); Department of Diagnostic Sciences, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3C, DK-2200 Copenhagen (Denmark); Logager, V.; Chabanova, E.; Thomsen, H.S. [Department of Diagnostic Radiology, Copenhagen University Hospital Herlev, Herlev Ringvej, DK-2730 Herlev (Denmark); Department of Diagnostic Sciences, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3C, DK-2200 Copenhagen (Denmark); Rosenberg, J. [Department of Surgical Gastroenterology D, Copenhagen University Hospital Herlev, Herlev Ringvej, DK-2730 Herlev (Denmark); Department of Diagnostic Sciences, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3C, DK-2200 Copenhagen (Denmark)

2010-06-15

Background: Colorectal cancer will present itself as a bowel obstruction in 16-23% of all cases. However, not all obstructing tumors are malignant and the differentiation between a benign and a malignant tumor can be difficult. The purpose of our study was to determine whether fast dynamic gadolinium-enhanced MR imaging combined with MR colonography could be used to differentiate a benign from a malignant obstructing colon tumor. Methods: Patients with benign colon tumor stenosis, based on diverticulitis, were asked to participate in the study. The same number of patients with verified colorectal cancer was included. Both groups had to be scheduled for surgery to be included. Two blinded observers analyzed the tumors on MR by placing a region of interest in the tumor and a series of parameters were evaluated, e.g. wash-in, wash-out and time-to-peak. Results: 14 patients were included. The wash-in and wash-out rates were significantly different between the benign and malignant tumors, and a clear distinction between benign and malignant disease was therefore possible by looking only at the MR data. Furthermore, MR colography evaluating the rest of the colon past the stenosis was possible with all patients. Conclusion: The results showed the feasibility of using fast dynamic gadolinium-enhanced MR imaging to differentiate between benign and malignant colonic tumors. With a high intra-class correlation and significant differences found on independent segments of the tumor, the method appears to be reproducible. Furthermore, the potential is big in performing a full preoperative colon evaluation even in patients with obstructing cancer. Trial number: (NCT00114829).

Texture-based classification of different gastric tumors at contrast-enhanced CT

Energy Technology Data Exchange (ETDEWEB)

Ba-Ssalamah, Ahmed, E-mail: ahmed.ba-ssalamah@meduniwien.ac.at [Department of Radiology, Medical University of Vienna (Austria); Muin, Dina; Schernthaner, Ruediger; Kulinna-Cosentini, Christiana; Bastati, Nina [Department of Radiology, Medical University of Vienna (Austria); Stift, Judith [Department of Pathology, Medical University of Vienna (Austria); Gore, Richard [Department of Radiology, University of Chicago Pritzker School of Medicine, Chicago, IL (United States); Mayerhoefer, Marius E. [Department of Radiology, Medical University of Vienna (Austria)

2013-10-01

Purpose: To determine the feasibility of texture analysis for the classification of gastric adenocarcinoma, lymphoma, and gastrointestinal stromal tumors on contrast-enhanced hydrodynamic-MDCT images. Materials and methods: The arterial phase scans of 47 patients with adenocarcinoma (AC) and a histologic tumor grade of [AC-G1, n = 4, G1, n = 4; AC-G2, n = 7; AC-G3, n = 16]; GIST, n = 15; and lymphoma, n = 5, and the venous phase scans of 48 patients with AC-G1, n = 3; AC-G2, n = 6; AC-G3, n = 14; GIST, n = 17; lymphoma, n = 8, were retrospectively reviewed. Based on regions of interest, texture analysis was performed, and features derived from the gray-level histogram, run-length and co-occurrence matrix, absolute gradient, autoregressive model, and wavelet transform were calculated. Fisher coefficients, probability of classification error, average correlation coefficients, and mutual information coefficients were used to create combinations of texture features that were optimized for tumor differentiation. Linear discriminant analysis in combination with a k-nearest neighbor classifier was used for tumor classification. Results: On arterial-phase scans, texture-based lesion classification was highly successful in differentiating between AC and lymphoma, and GIST and lymphoma, with misclassification rates of 3.1% and 0%, respectively. On venous-phase scans, texture-based classification was slightly less successful for AC vs. lymphoma (9.7% misclassification) and GIST vs. lymphoma (8% misclassification), but enabled the differentiation between AC and GIST (10% misclassification), and between the different grades of AC (4.4% misclassification). No texture feature combination was able to adequately distinguish between all three tumor types. Conclusion: Classification of different gastric tumors based on textural information may aid radiologists in establishing the correct diagnosis, at least in cases where the differential diagnosis can be narrowed down to two

Texture-based classification of different gastric tumors at contrast-enhanced CT

International Nuclear Information System (INIS)

Ba-Ssalamah, Ahmed; Muin, Dina; Schernthaner, Ruediger; Kulinna-Cosentini, Christiana; Bastati, Nina; Stift, Judith; Gore, Richard; Mayerhoefer, Marius E.

2013-01-01

Purpose: To determine the feasibility of texture analysis for the classification of gastric adenocarcinoma, lymphoma, and gastrointestinal stromal tumors on contrast-enhanced hydrodynamic-MDCT images. Materials and methods: The arterial phase scans of 47 patients with adenocarcinoma (AC) and a histologic tumor grade of [AC-G1, n = 4, G1, n = 4; AC-G2, n = 7; AC-G3, n = 16]; GIST, n = 15; and lymphoma, n = 5, and the venous phase scans of 48 patients with AC-G1, n = 3; AC-G2, n = 6; AC-G3, n = 14; GIST, n = 17; lymphoma, n = 8, were retrospectively reviewed. Based on regions of interest, texture analysis was performed, and features derived from the gray-level histogram, run-length and co-occurrence matrix, absolute gradient, autoregressive model, and wavelet transform were calculated. Fisher coefficients, probability of classification error, average correlation coefficients, and mutual information coefficients were used to create combinations of texture features that were optimized for tumor differentiation. Linear discriminant analysis in combination with a k-nearest neighbor classifier was used for tumor classification. Results: On arterial-phase scans, texture-based lesion classification was highly successful in differentiating between AC and lymphoma, and GIST and lymphoma, with misclassification rates of 3.1% and 0%, respectively. On venous-phase scans, texture-based classification was slightly less successful for AC vs. lymphoma (9.7% misclassification) and GIST vs. lymphoma (8% misclassification), but enabled the differentiation between AC and GIST (10% misclassification), and between the different grades of AC (4.4% misclassification). No texture feature combination was able to adequately distinguish between all three tumor types. Conclusion: Classification of different gastric tumors based on textural information may aid radiologists in establishing the correct diagnosis, at least in cases where the differential diagnosis can be narrowed down to two

Endothelial cells provide a notch-dependent pro-tumoral niche for enhancing breast cancer survival, stemness and pro-metastatic properties.

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Pegah Ghiabi

Full Text Available Treating metastasis has been challenging due to tumors complexity and heterogeneity. This complexity is partly related to the crosstalk between tumor and its microenvironment. Endothelial cells -the building blocks of tumor vasculature- have been shown to have additional roles in cancer progression than angiogenesis and supplying oxygen and nutrients. Here, we show an alternative role for endothelial cells in supporting breast cancer growth and spreading independent of their vascular functions. Using endothelial cells and breast cancer cell lines MDA-MB231 and MCF-7, we developed co-culture systems to study the influence of tumor endothelium on breast tumor development by both in vitro and in vivo approaches. Our results demonstrated that endothelial cells conferred survival advantage to tumor cells under complete starvation and enriched the CD44HighCD24Low/- stem cell population in tumor cells. Moreover, endothelial cells enhanced the pro-metastatic potential of breast cancer cells. The in vitro and in vivo results concordantly confirmed a role for endothelial Jagged1 to promote breast tumor through notch activation. Here, we propose a role for endothelial cells in enhancing breast cancer progression, stemness, and pro-metastatic traits through a perfusion-independent manner. Our findings may be beneficial in developing novel therapeutic approaches.

Whole Gene Capture Analysis of 15 CRC Susceptibility Genes in Suspected Lynch Syndrome Patients.

Science.gov (United States)

Jansen, Anne M L; Geilenkirchen, Marije A; van Wezel, Tom; Jagmohan-Changur, Shantie C; Ruano, Dina; van der Klift, Heleen M; van den Akker, Brendy E W M; Laros, Jeroen F J; van Galen, Michiel; Wagner, Anja; Letteboer, Tom G W; Gómez-García, Encarna B; Tops, Carli M J; Vasen, Hans F; Devilee, Peter; Hes, Frederik J; Morreau, Hans; Wijnen, Juul T

2016-01-01

Lynch Syndrome (LS) is caused by pathogenic germline variants in one of the mismatch repair (MMR) genes. However, up to 60% of MMR-deficient colorectal cancer cases are categorized as suspected Lynch Syndrome (sLS) because no pathogenic MMR germline variant can be identified, which leads to difficulties in clinical management. We therefore analyzed the genomic regions of 15 CRC susceptibility genes in leukocyte DNA of 34 unrelated sLS patients and 11 patients with MLH1 hypermethylated tumors with a clear family history. Using targeted next-generation sequencing, we analyzed the entire non-repetitive genomic sequence, including intronic and regulatory sequences, of 15 CRC susceptibility genes. In addition, tumor DNA from 28 sLS patients was analyzed for somatic MMR variants. Of 1979 germline variants found in the leukocyte DNA of 34 sLS patients, one was a pathogenic variant (MLH1 c.1667+1delG). Leukocyte DNA of 11 patients with MLH1 hypermethylated tumors was negative for pathogenic germline variants in the tested CRC susceptibility genes and for germline MLH1 hypermethylation. Somatic DNA analysis of 28 sLS tumors identified eight (29%) cases with two pathogenic somatic variants, one with a VUS predicted to pathogenic and LOH, and nine cases (32%) with one pathogenic somatic variant (n = 8) or one VUS predicted to be pathogenic (n = 1). This is the first study in sLS patients to include the entire genomic sequence of CRC susceptibility genes. An underlying somatic or germline MMR gene defect was identified in ten of 34 sLS patients (29%). In the remaining sLS patients, the underlying genetic defect explaining the MMRdeficiency in their tumors might be found outside the genomic regions harboring the MMR and other known CRC susceptibility genes.

Enhanced suppression of tumor growth by concomitant treatment of human lung cancer cells with suberoylanilide hydroxamic acid and arsenic trioxide

International Nuclear Information System (INIS)

Chien, Chia-Wen; Yao, Ju-Hsien; Chang, Shih-Yu; Lee, Pei-Chih; Lee, Te-Chang

2011-01-01

The efficacy of arsenic trioxide (ATO) against acute promyelocytic leukemia (APL) and relapsed APL has been well documented. ATO may cause DNA damage by generating reactive oxygen intermediates. Suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, modulates gene and protein expression via histone-dependent or -independent pathways that may result in chromatin decondensation, cell cycle arrest, differentiation, and apoptosis. We investigated whether ATO and SAHA act synergistically to enhance the death of cancer cells. Our current findings showed that combined treatment with ATO and SAHA resulted in enhanced suppression of non-small-cell lung carcinoma in vitro in H1299 cells and in vivo in a xenograft mouse model. Flow cytometric analysis of annexin V+ cells showed that apoptotic cell death was significantly enhanced after combined treatment with ATO and SAHA. At the doses used, ATO did not interfere with cell cycle progression, but SAHA induced p21 expression and led to G1 arrest. A Comet assay demonstrated that ATO, but not SAHA, induced DNA strand breaks in H1299 cells; however, co-treatment with SAHA significantly increased ATO-induced DNA damage. Moreover, SAHA enhanced acetylation of histone H3 and sensitized genomic DNA to DNase I digestion. Our results suggest that SAHA may cause chromatin relaxation and increase cellular susceptibility to ATO-induced DNA damage. Combined administration of SAHA and ATO may be an effective approach to the treatment of lung cancer. -- Highlights: ► ATO and SAHA are therapeutic agents with different action modes. ► Combination of ATO and SAHA synergistically inhibits tumor cell growth. ► SAHA loosens chromatin structure resulting in increased sensitivity to DNase I. ► ATO-induced DNA damage and apoptosis are enhanced by co-treatment with SAHA.

Differential diagnosis between metastatic tumors and nonsolid benign lesions of the liver using ferucarbotran-enhanced MR imaging

Energy Technology Data Exchange (ETDEWEB)

Higashihara, Hiroki [Department of Radiology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 5650871 (Japan)], E-mail: h-higashihara@radiol.med.osaka-u.ac.jp; Murakami, Takamichi [Department of Radiology, Kinki University School of Medicine 377-2 Oonohigashi, Osakasayama, Osaka 5898511 (Japan); Kim, Tonsok; Hori, Masatoshi; Onishi, Hiromitsu [Department of Radiology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 5650871 (Japan); Nakata, Saki [Department of Radiology, Toyonaka Municipal Hospital, 4-14-1 Shibahara Chou, Toyonaka, Osaka 5608565 (Japan); Osuga, Keigo; Tomoda, Kaname; Nakamura, Hironobu [Department of Radiology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 5650871 (Japan)

2010-01-15

Purpose: To evaluate ability of ferucarbotran-enhanced MR imaging (MRI) in differentiating metastases from nonsolid benign lesions of the liver according to signal-intensity characteristics. Materials and methods: Sixty-six consecutive patients, who had 138 focal hepatic lesions (26 cysts, 11 hemangiomas, and 101 metastases), underwent ferucarbotran-enhanced MRI. The signal-intensity pattern of each kind of lesion relative to the liver parenchyma on ferucarbotran-enhanced T2* and heavily T1-weighted gradient-echo images were assessed and categorized into the following three categories: high-intensity and iso-intensity, respectively (category A), high and low (category B), and iso- and low-intensity (category C). For category B, lesions were subdivided into two groups based on single-shot half-Fourier RARE images: category B1 (not significantly high-intensity) and category B2 (significantly high-intensity). Results: Category A had 11 hemangiomas and 2 metastatic tumors, category B1 had 97 metastatic tumors, category B2 had 2 metastatic tumors and 9 cysts, and category C had 17 cysts. When a tumor with a signal intensity of category A was considered to be hemangioma, category B1 metastasis, and category B2 and C cyst, the diagnostic accuracy for differentiating these lesions was 97% (134/138). Conclusion: The combination of signal-intensity pattern on ferucarbotran-enhanced T2*- and heavily T1-weighted gradient-echo MRI has ability to differentiate liver metastases from nonsolid benign lesions. However, T2-weighted single-shot half-Fourier RARE imaging should also be employed to achieve better performance.

Can quantitative contrast-enhanced ultrasonography predict cervical tumor response to neoadjuvant chemotherapy?

Energy Technology Data Exchange (ETDEWEB)

Peng, Chuan; Liu, Long-Zhong; Zheng, Wei [Department of Ultrasound, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060 (China); Xie, Yan-Jun [Department of Gynecology and Obstetrics, Zhongcun Town hospital, 140 Renmin Road, Zhongcun Town, Panyu District, Guangzhou, 511400 (China); Xiong, Yong-Hong; Li, An-Hua [Department of Ultrasound, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060 (China); Pei, Xiao-Qing, E-mail: peixq@sysucc.org.cn [Department of Ultrasound, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060 (China)

2016-11-15

Highlights: • We assessed the clinical value of quantitative CEUS for prediction of cervical tumor perfusion response to NACT. • IMAX, RT, and TTP changed significantly after one NACT cycle. • Pre-treatment IMAX positively correlated with the absolute and percentage changes in all cervical tumor IMAX after NACT. • Pre-treatment IMAX may be predictive of NACT perfusion response in cervical tumor. - Abstract: Objective: To evaluate the feasibility of quantitative contrast-enhanced ultrasonography (CEUS) for predicting and assessing cervical tumor response to neoadjuvant chemotherapy (NACT). Methods: Thirty-eight cases with stage IB2 or IIA cervical cancer were studied using CEUS before and after one cycle of NACT. The quantitative CEUS parameters maximum intensity (IMAX), rise time (RT), time to peak (TTP), and mean transit time (MTT) were compared between cervical tumors and myometrium (reference zone) using Sonoliver software. Absolute and relative changes in quantitative CEUS parameters were also compared among complete response, partial response, and non-responsive groups. Correlations between pre-treatment IMAX and changes in quantitative parameters were assessed after one cycle of NACT. Results: There were significant changes in cervical tumor IMAX (P < 0.001), RT (P < 0.05), and TTP (P < 0.05) after one cycle of NACT. According to the Response Evaluation Criteria In Solid Tumors guidelines, the enrollments were divided into complete response, partial response, stable disease and progressive disease groups. There were no significant differences in quantitative CEUS parameters among complete response, partial response, and non-responsive groups (P > 0.05). In the stable disease group (n = 17), cervical tumor IMAX, RT, and TTP decreased significantly after NACT (P < 0.001). The absolute and percentage changes in IMAX were positively correlated with pre-treatment IMAX in all 38 patients (r = 0.576, P < 0.001 and r = 0.429, P < 0.001). Conclusion

Swarm Intelligence-Enhanced Detection of Non-Small-Cell Lung Cancer Using Tumor-Educated Platelets

NARCIS (Netherlands)

Best, Myron G.; Sol, Nik; In ‘t Veld, Sjors G.J.G.; Vancura, Adrienne; Muller, Mirte; Niemeijer, Anna Larissa N.; Fejes, Aniko V.; Tjon Kon Fat, Lee Ann; Huis in 't Veld, Anna E; Leurs, Cyra; Le Large, Tessa Y.; Meijer, Laura L.; Kooi, Irsan E.; Rustenburg, François; Schellen, Pepijn; Verschueren, Heleen; Post, Edward; Wedekind, Laurine E.; Bracht, Jillian; Esenkbrink, Michelle; Wils, Leon; Favaro, Francesca; Schoonhoven, Jilian D.; Tannous, Jihane; Meijers-Heijboer, Hanne; Kazemier, Geert; Giovannetti, Elisa; Reijneveld, Jaap C.; Idema, Sander; Killestein, Joep; Heger, Michal; de Jager, Saskia C.; Urbanus, Rolf T.; Hoefer, Imo E.; Pasterkamp, Gerard; Mannhalter, Christine; Gomez-Arroyo, Jose; Bogaard, Harm-Jan; Noske, David P.; Vandertop, W. Peter; van den Broek, Daan; Ylstra, Bauke; Nilsson, R. Jonas A; Wesseling, Pieter; Karachaliou, Niki; Rosell, Rafael; Lee-Lewandrowski, Elizabeth; Lewandrowski, Kent B.; Tannous, Bakhos A.; de Langen, Adrianus J.; Smit, Egbert F.; van den Heuvel, Michel M; Wurdinger, Thomas

2017-01-01

Blood-based liquid biopsies, including tumor-educated blood platelets (TEPs), have emerged as promising biomarker sources for non-invasive detection of cancer. Here we demonstrate that particle-swarm optimization (PSO)-enhanced algorithms enable efficient selection of RNA biomarker panels from

Dose enhancement in radiotherapy of small lung tumors using inline magnetic fields: A Monte Carlo based planning study

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Oborn, B. M., E-mail: brad.oborn@gmail.com [Illawarra Cancer Care Centre (ICCC), Wollongong, NSW 2500, Australia and Centre for Medical Radiation Physics (CMRP), University of Wollongong, Wollongong, NSW 2500 (Australia); Ge, Y. [Sydney Medical School, University of Sydney, NSW 2006 (Australia); Hardcastle, N. [Northern Sydney Cancer Centre, Royal North Shore Hospital, Sydney, NSW 2065 (Australia); Metcalfe, P. E. [Centre for Medical Radiation Physics (CMRP), University of Wollongong, Wollongong NSW 2500, Australia and Ingham Institute for Applied Medical Research, Liverpool, NSW 2170 (Australia); Keall, P. J. [Sydney Medical School, University of Sydney, NSW 2006, Australia and Ingham Institute for Applied Medical Research, Liverpool, NSW 2170 (Australia)

2016-01-15

Purpose: To report on significant dose enhancement effects caused by magnetic fields aligned parallel to 6 MV photon beam radiotherapy of small lung tumors. Findings are applicable to future inline MRI-guided radiotherapy systems. Methods: A total of eight clinical lung tumor cases were recalculated using Monte Carlo methods, and external magnetic fields of 0.5, 1.0, and 3 T were included to observe the impact on dose to the planning target volume (PTV) and gross tumor volume (GTV). Three plans were 6 MV 3D-CRT plans while 6 were 6 MV IMRT. The GTV’s ranged from 0.8 to 16 cm{sup 3}, while the PTV’s ranged from 1 to 59 cm{sup 3}. In addition, the dose changes in a 30 cm diameter cylindrical water phantom were investigated for small beams. The central 20 cm of this phantom contained either water or lung density insert. Results: For single beams, an inline magnetic field of 1 T has a small impact in lung dose distributions by reducing the lateral scatter of secondary electrons, resulting in a small dose increase along the beam. Superposition of multiple small beams leads to significant dose enhancements. Clinically, this process occurs in the lung tissue typically surrounding the GTV, resulting in increases to the D{sub 98%} (PTV). Two isolated tumors with very small PTVs (3 and 6 cm{sup 3}) showed increases in D{sub 98%} of 23% and 22%. Larger PTVs of 13, 26, and 59 cm{sup 3} had increases of 9%, 6%, and 4%, describing a natural fall-off in enhancement with increasing PTV size. However, three PTVs bounded to the lung wall showed no significant increase, due to lack of dose enhancement in the denser PTV volume. In general, at 0.5 T, the GTV mean dose enhancement is around 60% lower than that at 1 T, while at 3 T, it is 5%–60% higher than 1 T. Conclusions: Monte Carlo methods have described significant and predictable dose enhancement effects in small lung tumor plans for 6 MV radiotherapy when an external inline magnetic field is included. Results of this study

The vascular disrupting agent ZD6126 shows increased antitumor efficacy and enhanced radiation response in large, advanced tumors

International Nuclear Information System (INIS)

Siemann, Dietmar W.; Rojiani, Amyn M.

2005-01-01

Purpose: ZD6126 is a vascular-targeting agent that induces selective effects on the morphology of proliferating and immature endothelial cells by disrupting the tubulin cytoskeleton. The efficacy of ZD6126 was investigated in large vs. small tumors in a variety of animal models. Methods and Materials: Three rodent tumor models (KHT, SCCVII, RIF-1) and three human tumor xenografts (Caki-1, KSY-1, SKBR3) were used. Mice bearing leg tumors ranging in size from 0.1-2.0 g were injected intraperitoneally with a single 150 mg/kg dose of ZD6126. The response was assessed by morphologic and morphometric means as well as an in vivo to in vitro clonogenic cell survival assay. To examine the impact of tumor size on the extent of enhancement of radiation efficacy by ZD6126, KHT sarcomas of three different sizes were irradiated locally with a range of radiation doses, and cell survival was determined. Results: All rodent tumors and human tumor xenografts evaluated showed a strong correlation between increasing tumor size and treatment effect as determined by clonogenic cell survival. Detailed evaluation of KHT sarcomas treated with ZD6126 showed a reduction in patent tumor blood vessels that was ∼20% in small ( 90% in large (>1.0 g) tumors. Histologic assessment revealed that the extent of tumor necrosis after ZD6126 treatment, although minimal in small KHT sarcomas, became more extensive with increasing tumor size. Clonogenic cell survival after ZD6126 exposure showed a decrease in tumor surviving fraction from approximately 3 x 10 -1 to 1 x 10 -4 with increasing tumor size. When combined with radiotherapy, ZD6126 treatment resulted in little enhancement of the antitumor effect of radiation in small (<0.3 g) tumors but marked increases in cell kill in tumors larger than 1.0 g. Conclusions: Because bulky neoplastic disease is typically the most difficult to manage, the present findings provide further support for the continued development of vascular disrupting agents such as

Experimental assessment of the role of the blood flow inhibition in hyperglycemia-enhanced radiation injury to tumor

International Nuclear Information System (INIS)

Kozin, S.V.; Sevast'yanov, A.I.; Yarmonenko, S.P.

1986-01-01

Experimental assessment of the role of the blood flow inhibition in enhancement of radiation injury to tumors using short-term hyperglycemia was provided. Experiments on mice with Ehrlich solid carcinoma showed the dependence of a rise of the antitumor effect of preceding radiation induced by glucose and glucose combined with mexamin on a degree of the blood flow inhibition under the influence of these modifying agents. It was established that a considerable enhancement of radiation injury occured but in such tumors where short-term hyperglycemia and mexamin decreased the blood flow level not less than 5-10 fold as estimated by 133 Xe clearance. The results of the above experiments showed that the noticeable inhibition of the blood flow in tumors was a necessary tough, probably, not the only condition for a high efficacy of short-term hyperglycemia used an ajuvant to radiotherapy

Synergistic retention strategy of RGD active targeting and radiofrequency-enhanced permeability for intensified RF & chemotherapy synergistic tumor treatment.

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Zhang, Kun; Li, Pei; He, Yaping; Bo, Xiaowan; Li, Xiaolong; Li, Dandan; Chen, Hangrong; Xu, Huixiong

2016-08-01

Despite gaining increasing attention, chelation of multiple active targeting ligands greatly increase the formation probability of protein corona, disabling active targeting. To overcome it, a synergistic retention strategy of RGD-mediated active targeting and radiofrequency (RF) electromagnetic field-enhanced permeability has been proposed here. It is validated that such a special synergistic retention strategy can promote more poly lactic-co-glycolic acid (PLGA)-based capsules encapsulating camptothecin (CPT) and solid DL-menthol (DLM) to enter and retain in tumor in vitro and in vivo upon exposure to RF irradiation, receiving an above 8 fold enhancement in HeLa retention. Moreover, the PLGA-based capsules can respond RF field to trigger the entrapped DLM to generate solid-liquid-gas (SLG) tri-phase transformation for enhancing RF ablation and CPT release. Therefore, depending on the enhanced RF ablation and released CPT and the validated synergistic retention effect, the inhibitory outcome for tumor growth has gained an over 10-fold improvement, realizing RF ablation & chemotherapy synergistic treatment against HeLa solid tumor, which indicates a significant promise in clinical RF ablation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Contrast-enhanced ultrasound and computed tomography findings of recurrent ovarian steroid cell tumor presenting with peritoneal seeding: A case report

International Nuclear Information System (INIS)

Im, A Lan; Lee, Young Hwan; Kim, Hye Won; Lee, Han Ah; Choi, Keum Ha

2013-01-01

We present ultrasonography and computed tomography (CT) findings of a case of recurrent ovarian steroid cell tumor presenting with peritoneal seeding in a 45-year-old woman. On abdominal ultrasonography, there were multiple hypoechoic round masses in the peritoneal cavity including the perihepatic area. Contrast-enhanced ultrasonography showed intense homogenous enhancement on the arterial phase and delayed prolonged enhancement of the masses. CT revealed multiple peritoneal solid masses with strong enhancement. Five years ago, the patient had been diagnosed with a steroid cell tumor of the left ovary. At that time, the CT showed a well-enhancing, lobulating, large solid mass at the left adnexa. Imaging findings of the peritoneal masses suggested peritoneal seeding from the preexisting ovarian steroid cell tumor. For treatment of the metastatic lesions in the perihepatic area, ultrasonography-guided radiofrequency ablation (RFA) was performed, and debulking surgery for the peritoneal masses was done. Six months later, complete ablation of the perihepatic metastases by RFA and a marked decrease in the peritoneal metastases by surgery were found on the follow-up CT.

Polydopamine-coated gold nanostars for CT imaging and enhanced photothermal therapy of tumors

Science.gov (United States)

Li, Du; Shi, Xiangyang; Jin, Dayong

2016-12-01

The advancement of biocompatible nanoplatforms with dual functionalities of diagnosis and therapeutics is strongly demanded in biomedicine in recent years. In this work, we report the synthesis and characterization of polydopamine (pD)-coated gold nanostars (Au NSs) for computed tomography (CT) imaging and enhanced photothermal therapy (PTT) of tumors. Au NSs were firstly formed via a seed-mediated growth method and then stabilized with thiolated polyethyleneimine (PEI-SH), followed by deposition of pD on their surface. The formed pD-coated Au NSs (Au-PEI@pD NSs) were well characterized. We show that the Au-PEI@pD NSs are able to convert the absorbed near-infrared laser light into heat, and have strong X-ray attenuation property. Due to the co-existence of Au NSs and the pD, the light to heat conversion efficiency of the NSs can be significantly enhanced. These very interesting properties allow their uses as a powerful theranostic nanoplatform for efficient CT imaging and enhanced phtotothermal therapy of cancer cells in vitro and the xenografted tumor model in vivo. With the easy functionalization nature enabled by the coated pD shell, the developed pD-coated Au NSs may be developed as a versatile nanoplatform for targeted CT imaging and PTT of different types of cancer.

T-regulatory cells depletion is the main cause for enhanced antitumor immunity during radio-sensitization of tumors by 2-deoxy-D-glucose

International Nuclear Information System (INIS)

Farooque, Abdullah; Verma, Amit; Singh, Niharika; Chauhan, Sachin Kumar Singh; Jethani, Jyoti; Adhikari, J.S.; Dwarakanath, B.S.; Afrin, Farhat

2014-01-01

Regulatory T cells (Tregs) are known to have profound effects in blocking anti-tumor immunity. Therefore, Tregs are seen as a major hurdle that must be overcome in order to improve the efficacy of cancer therapy. The glycolytic inhibitor, 2-deoxy-d-glucose (2-DG) enhances radiation and chemotherapeutics induced death of many cancer cells in vitro and local tumor control in vivo, which was found to be associated with the enhanced anti-tumor immunity. Therefore, we investigated the role of Tregs in determining the tumor response to the combined treatment of 2-DG plus ionizing radiation. Ehrlich ascites tumor bearing mice were administered with a single dose of 2-DG (2 gm/Kg/b.wt) intravenously just before focal irradiation (10 Gy). Immuno-phenotyping of Tregs in secondary lymphoid organs was carried out using flow cytometry, while related cytokines were analyzed using bead array and ELISA. Further, mRNA and protein levels of transcription factors were assessed in sorted splenic CD4 + cells and CD4 + CD25 + using real time PCR and Western blot techniques. Results clearly showed depletion (TRAIL mediated apoptosis) of T regs (CD4 + CD25 + FoxP3 + CD39 + FR4 + GITR + CD127 - ), in blood, spleen, lymph node and tumor following the combined treatment. This led to the immune activation in the periphery, secondary lymphoid organs and massive infiltration of CD4 + , CD8 + and NK cells in the tumor, which correlated well with the complete response (cure; tumor free survival). Association of Treg depletion with the tumor response was further confirmed using low doses of cyclophosphamide (which depletes Tegs) and rapamycin (activator of Tregs),wherein the depletor of Tregs enhanced the efficacy of combined treatment, while Tregs enhancer compromised the efficacy. These studies unequivocally established the role of Tregs in determining the therapeutic response and can be used as a target for enhancing the efficacy of this combined treatment, besides establishing the potential of

MUC1 enhances tumor progression and contributes toward immunosuppression in a mouse model of spontaneous pancreatic adenocarcinoma.

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Tinder, Teresa L; Subramani, Durai B; Basu, Gargi D; Bradley, Judy M; Schettini, Jorge; Million, Arefayene; Skaar, Todd; Mukherjee, Pinku

2008-09-01

MUC1, a membrane tethered mucin glycoprotein, is overexpressed and aberrantly glycosylated in >80% of human ductal pancreatic adenocarcinoma. However, the role of MUC1 in pancreatic cancer has been elusive, partly due to the lack of an appropriate model. We report the characterization of a novel mouse model that expresses human MUC1 as a self molecule (PDA.MUC1 mice). Pancreatic tumors arise in an appropriate MUC1-tolerant background within an immune-competent host. Significant enhancement in the development of pancreatic intraepithelial preneoplastic lesions and progression to adenocarcinoma is observed in PDA.MUC1 mice, possibly due to increased proliferation. Tumors from PDA.MUC1 mice express higher levels of cyclooxygenase-2 and IDO compared with PDA mice lacking MUC1, especially during early stages of tumor development. The increased proinflammatory milieu correlates with an increased percentage of regulatory T cells and myeloid suppressor cells in the pancreatic tumor and tumor draining lymph nodes. Data shows that during pancreatic cancer progression, MUC1-mediated mechanisms enhance the onset and progression of the disease, which in turn regulate the immune responses. Thus, the mouse model is ideally suited for testing novel chemopreventive and therapeutic strategies against pancreatic cancer.

MUC1 enhances tumor progression and contributes towards immunosuppression in a mouse model of spontaneous pancreatic adenocarcinoma

Science.gov (United States)

Tinder, Teresa L.; Subramani, Durai B.; Basu, Gargi D.; Bradley, Judy M.; Schettini, Jorge; Million, Arefayene; Skaar, Todd

2008-01-01

MUC1, a membrane tethered mucin glycoprotein, is overexpressed and aberrantly glycosylated in >80% of human ductal pancreatic adenocarcinoma. However, the role of MUC1 in pancreatic cancer has been elusive, partly due to the lack of an appropriate model. We report the characterization of a novel mouse model that expresses human MUC1 as a self molecule (PDA.MUC1 mice). Pancreatic tumors arise in an appropriate MUC1-tolerant background within an immune competent host. Significant enhancement in the development of pancreatic intraepithelial pre-neoplastic lesions (PanINs) and progression to adenocarcinoma is observed in PDA.MUC1 mice, possibly due to increased proliferation. Tumors from PDA.MUC1 mice express higher levels of cyclooxygenase-2 and indoleamine 2,3, dioxygenase compared to PDA mice lacking MUC1, especially during early stages of tumor development. The increased pro-inflammatory milieu correlates with an increased percentage of regulatory T cells and myeloid suppressor cells in the pancreatic tumor and tumor draining lymph nodes. Data shows that during pancreatic cancer progression, MUC1-mediated mechanisms enhance the onset and progression of the disease which in turn regulate the immune responses. Thus, the mouse model is ideally-suited for testing novel chemopreventive and therapeutic strategies against pancreatic cancer. PMID:18713982

Alternating current electrical stimulation enhanced chemotherapy: a novel strategy to bypass multidrug resistance in tumor cells

International Nuclear Information System (INIS)

Janigro, Damir; Perju, Catalin; Fazio, Vincent; Hallene, Kerri; Dini, Gabriele; Agarwal, Mukesh K; Cucullo, Luca

2006-01-01

Tumor burden can be pharmacologically controlled by inhibiting cell division and by direct, specific toxicity to the cancerous tissue. Unfortunately, tumors often develop intrinsic pharmacoresistance mediated by specialized drug extrusion mechanisms such as P-glycoprotein. As a consequence, malignant cells may become insensitive to various anti-cancer drugs. Recent studies have shown that low intensity very low frequency electrical stimulation by alternating current (AC) reduces the proliferation of different tumor cell lines by a mechanism affecting potassium channels while at intermediate frequencies interfere with cytoskeletal mechanisms of cell division. The aim of the present study is to test the hypothesis that permeability of several MDR1 over-expressing tumor cell lines to the chemotherapic agent doxorubicin is enhanced by low frequency, low intensity AC stimulation. We grew human and rodent cells (C6, HT-1080, H-1299, SKOV-3 and PC-3) which over-expressed MDR1 in 24-well Petri dishes equipped with an array of stainless steel electrodes connected to a computer via a programmable I/O board. We used a dedicated program to generate and monitor the electrical stimulation protocol. Parallel cultures were exposed for 3 hours to increasing concentrations (1, 2, 4, and 8 μM) of doxorubicin following stimulation to 50 Hz AC (7.5 μA) or MDR1 inhibitor XR9576. Cell viability was assessed by determination of adenylate kinase (AK) release. The relationship between MDR1 expression and the intracellular accumulation of doxorubicin as well as the cellular distribution of MDR1 was investigated by computerized image analysis immunohistochemistry and Western blot techniques. By the use of a variety of tumor cell lines, we show that low frequency, low intensity AC stimulation enhances chemotherapeutic efficacy. This effect was due to an altered expression of intrinsic cellular drug resistance mechanisms. Immunohistochemical, Western blot and fluorescence analysis revealed

Acidity-Triggered Tumor Retention/Internalization of Chimeric Peptide for Enhanced Photodynamic Therapy and Real-Time Monitoring of Therapeutic Effects.

Science.gov (United States)

Han, Kai; Zhang, Wei-Yun; Ma, Zhao-Yu; Wang, Shi-Bo; Xu, Lu-Ming; Liu, Jia; Zhang, Xian-Zheng; Han, He-You

2017-05-17

Photodynamic therapy (PDT) holds great promise in tumor treatment. Nevertheless, it remains highly desirable to develop easy-to-fabricated PDT systems with improved tumor accumulation/internalization and timely therapeutic feedback. Here, we report a tumor-acidity-responsive chimeric peptide for enhanced PDT and noninvasive real-time apoptosis imaging. Both in vitro and in vivo studies revealed that a tumor mildly acidic microenvironment could trigger rapid protonation of carboxylate anions in chimeric peptide, which led to increased ζ potential, improved hydrophobicity, controlled size enlargement, and precise morphology switching from sphere to spherocylinder shape of the chimeric peptide. All of these factors realized superfast accumulation and prolonged retention in the tumor region, selective cellular internalization, and enhanced PDT against the tumor. Meanwhile, this chimeric peptide could further generate reactive oxygen species and initiate cell apoptosis during PDT. The subsequent formation of caspase-3 enzyme hydrolyzed the chimeric peptide, achieving a high signal/noise ratio and timely fluorescence feedback. Importantly, direct utilization of the acidity responsiveness of a biofunctional Asp-Glu-Val-Asp-Gly (DEVDG, caspase-3 enzyme substrate) peptide sequence dramatically simplified the preparation and increased the performance of the chimeric peptide furthest.

Hydrothermally synthesized PEGylated calcium phosphate nanoparticles incorporating Gd-DTPA for contrast enhanced MRI diagnosis of solid tumors.

Science.gov (United States)

Mi, Peng; Kokuryo, Daisuke; Cabral, Horacio; Kumagai, Michiaki; Nomoto, Takahiro; Aoki, Ichio; Terada, Yasuko; Kishimura, Akihiro; Nishiyama, Nobuhiro; Kataoka, Kazunori

2014-01-28

Organic-inorganic hybrid nanoparticles with calcium phosphate (CaP) core and PEGylated shell were developed to incorporate magnetic resonance imaging (MRI) contrast agent diethylenetriaminepentaacetic acid gadolinium (III) (Gd-DTPA) for noninvasive diagnosis of solid tumors. A two-step preparation method was applied to elaborate hybrid nanoparticles with a z-average hydrodynamic diameter about 80nm, neutral surface ξ-potential and high colloidal stability in physiological environments by self-assembly of poly(ethylene glycol)-b-poly(aspartic acid) block copolymer, Gd-DTPA, and CaP in aqueous solution, followed with hydrothermal treatment. Incorporation into the hybrid nanoparticles allowed Gd-DTPA to show significant enhanced retention ratio in blood circulation, leading to high accumulation in tumor positions due to enhanced permeability and retention (EPR) effect. Moreover, Gd-DTPA revealed above 6 times increase of relaxivity in the nanoparticle system compared to free form, and eventually, selective and elevated contrast enhancements in the tumor positions were observed. These results indicate the high potential of Gd-DTPA-loaded PEGylated CaP nanoparticles as a novel contrast agent for noninvasive cancer diagnosis. Copyright © 2013 Elsevier B.V. All rights reserved.

Nanodiamond-Manganese dual mode MRI contrast agents for enhanced liver tumor detection.

Science.gov (United States)

Hou, Weixin; Toh, Tan Boon; Abdullah, Lissa Nurrul; Yvonne, Tay Wei Zheng; Lee, Kuan J; Guenther, Ilonka; Chow, Edward Kai-Hua

2017-04-01

Contrast agent-enhanced magnetic resonance (MR) imaging is critical for the diagnosis and monitoring of a number of diseases, including cancer. Certain clinical applications, including the detection of liver tumors, rely on both T1 and T2-weighted images even though contrast agent-enhanced MR imaging is not always reliable. Thus, there is a need for improved dual mode contrast agents with enhanced sensitivity. We report the development of a nanodiamond-manganese dual mode contrast agent that enhanced both T1 and T2-weighted MR imaging. Conjugation of manganese to nanodiamonds resulted in improved longitudinal and transverse relaxivity efficacy over unmodified MnCl 2 as well as clinical contrast agents. Following intravenous administration, nanodiamond-manganese complexes outperformed current clinical contrast agents in an orthotopic liver cancer mouse model while also reducing blood serum concentration of toxic free Mn 2+ ions. Thus, nanodiamond-manganese complexes may serve as more effective dual mode MRI contrast agent, particularly in cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

The usefulness of contrast-enhanced sonography in the differential diagnostic of adrenal tumors

International Nuclear Information System (INIS)

Slonina, J.; Nienartowicz, E.; Malczewska, J.; Moron, K.; Kumar Agrawal, A.

2006-01-01

Introduction: The occurrence of gland tumors causes significant clinical problem. Non hormone-secreting tumors provide the most complicated diagnostic difficulties. The application of contrast-enhanced sonography could improve the vessels visualization and point out characteristic features of benign and malignant changes. The authors believe that this new method make possible the differential adrenal tumor diagnostic process more precise and increase the specificity of ultrasonography in the recognition of benign and malignant tumors. The aim of this study was to define the usefulness of contrasting agent Levovist in differential diagnostics of adrenal tumors and its influence on sensitivity and specificity of ultrasound examination and to establish patients qualification criteria for surgical procedures. Material and methods: Ultrasound examinations were made with the use of digital devise by GE Voluson 740, probe 4.6 MHz with Doppler options and volumetric probe 3D according to the following protocol: 26 patients with recognized adrenal tumor were qualified for the examination. Patients in the first stage of tumor vascularisation had Doppler examination with color (CD) and power Doppler (PD). Three-dimensional ultrasonography was used to improve visualization of vascularisation. In the final phase of the examination the patients were administrated of Levovist in the recommended by the producer dose: 2,5 g in the concentration of 400 mg/l. Results: 26 cases of adrenal gland tumours were subjected to analysis. In standard ultrasonographic examination focal changes in 25 patients were hipoechogenic focuses and in one case the focus was hyperechogenic. Heterogeneity of focuses was observed in 16 cases. In Doppler examination with color (CD) and power Doppler (PD) vascular blood flow was revealed within 12. After using contrasting agent Levovist vascular blood flow was achieved in 4 additional cases, which constituted 61% . Conclusions: 1. 3D ultrasound could be

Time as An Important Soil-Forming Factor Influencing Modern and Ancient Magnetic Susceptibility Enhancement Along the Delaware River Valley, USA

Science.gov (United States)

Stinchcomb, G. E.; Peppe, D. J.; Driese, S. G.

2011-12-01

Magnetic susceptibility is an increasingly popular low-cost method for rapidly assessing paleoclimate and paleoenvironmental impact on buried soils. The goal of this study is to determine the primary influence(s) on soil magnetic susceptibility along floodplain, terrace and upland soils in the middle Delaware River Valley, USA, using environmental magnetic, pedologic, and stratigraphic techniques. Two-hundred thirty samples were collected from age-constrained sandy, quartz-rich, floodplain, terrace, and upland soils (Entisols, Inceptisols). A Kruskal-Wallis (K-W) and post-hoc Tukey-Kramer (T-K) (α=0.05) multiple comparisons analysis on 176 mass-specific low-field susceptibility (Xlf) assays show that A and B horizons are magnetically enhanced compared to C and E horizons (ptesting show that Xlf results, when grouped by floodplain-terrace designation (i.e., chronofunction) are significantly different (p<0.0001). The older T3 terrace and upland Xlf values (0.34±0.14 10^-6 m^3 kg^-1) are greater than the younger T2 terrace (0.18±0.06 10^-6 m^3 kg^-1) values, which are greater than modern floodplain (0.09±0.01 10^-6 m^3 kg^-1) Xlf values. These data suggest that longer intervals of soil formation enhance the Χlf value. This hypothesis is further supported when 159 Xlf values are plotted vs. age for the entire Holocene. A locally-weighted regression smoothing curve (LOESS) shows two distinct intervals of magnetic enhancement during previously established dry intervals, the early and late-middle Holocene. We hypothesize that prolonged drought during the early and middle Holocene reduced flood frequency and magnitude and the likelihood of soil burial, resulting in longer soil forming intervals and higher Xlf values. Although precipitation influences the Xlf signature, the results from this study suggest that the magnetic susceptibility values of well-drained buried floodplain soils along the Delaware River Valley are partly a function of time.

Minor salivary gland tumors in the oral cavity: Diagnostic value of dynamic contrast-enhanced MRI

International Nuclear Information System (INIS)

Matsuzaki, Hidenobu; Yanagi, Yoshinobu; Hara, Marina; Katase, Naoki; Asaumi, Jun-ichi; Hisatomi, Miki; Unetsubo, Teruhisa; Konouchi, Hironobu; Takenobu, Toshihiko; Nagatsuka, Hitoshi

2012-01-01

Objective: To evaluate the diagnostic value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for minor salivary gland tumors in the oral cavity. Materials and methods: Thirty-two patients with minor salivary gland tumors were examined preoperatively using DCE-MRI. Their maximum contrast index (CImax), time of CImax (Tmax), Tpeak; i.e., the time that corresponded to the CImax × 0.90, and washout ratios (WR300 and WR600) were determined from contrast index (CI) curves. We compared these parameters between benign and malignant tumors and among the different histopathological types of minor salivary gland tumors. Then, we categorized the patients’ CI curves into four patterns (gradual increase, rapid increase with high washout ratio, rapid increase with low washout, and flat). Results: Statistically significant differences in Tmax (P = 0.004) and Tpeak (P = 0.002) were observed between the benign and malignant tumors. Regarding each histopathological tumor type, significant differences in Tmax (P < 0.001), Tpeak (P < 0.001), and WR600 (P = 0.026) were observed between the pleomorphic adenomas and mucoepidermoid carcinomas. It was difficult to distinguish between benign and malignant tumors using our CI curve classification because that two-thirds of the cases were classified into the same type (gradual increase). Conclusion: The DCE-MRI parameters of minor salivary gland tumors contributed little to their differential diagnosis compared with those for major salivary gland tumors. During the diagnosis of minor salivary gland tumors, Tmax is useful for distinguishing between benign and malignant tumors

Differentiation between vasogenic-edema versus tumor-infiltrative area in patients with glioblastoma during bevacizumab therapy: A longitudinal MRI study

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Artzi, Moran, E-mail: artzimy@gmail.com [Functional Brain Center, Tel Aviv Sourasky Medical Center, Tel Aviv (Israel); Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Israel); Bokstein, Felix, E-mail: felixb@tlvmc.gov.il [Neuro-Oncology Service, Tel Aviv Sourasky Medical Center, Tel Aviv (Israel); Blumenthal, Deborah T., E-mail: deborahblumenthal@gmail.com [Neuro-Oncology Service, Tel Aviv Sourasky Medical Center, Tel Aviv (Israel); Aizenstein, Orna, E-mail: Ornaaizenstein@gmail.com [Functional Brain Center, Tel Aviv Sourasky Medical Center, Tel Aviv (Israel); Liberman, Gilad, E-mail: giladliberman@gmail.com [Functional Brain Center, Tel Aviv Sourasky Medical Center, Tel Aviv (Israel); Gonda Multidisciplinary Brain Research Center, Bar Ilan University, Ramat Gan (Israel); Corn, Benjamin W., E-mail: bencorn@tlvmc.gov.il [Functional Brain Center, Tel Aviv Sourasky Medical Center, Tel Aviv (Israel); Institute of Radiotherapy, Tel Aviv Sourasky Medical Center, Tel Aviv (Israel); Ben Bashat, Dafna, E-mail: dafnab@tlvmc.gov.il [Functional Brain Center, Tel Aviv Sourasky Medical Center, Tel Aviv (Israel); Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Israel); Sagol School of Neuroscience, Tel Aviv University, Tel Aviv (Israel)

2014-07-15

Background: Treatment with bevacizumab is associated with substantial radiologic response in patients with glioblastoma (GB). However, following this initial response, changes in T{sub 2}-weighted MRI signal may develop, suggesting an infiltrative pattern of tumor progression. The aim of this study was to differentiate between vasogenic-edema versus tumor-infiltrative area in GB patients. Methods and materials: Fourteen patients with GB were longitudinally scanned, before and during intravenous bevacizumab therapy (5/10 mg/kg every 2-weeks). A total of 40 MR scans including conventional, diffusion, dynamic susceptibility contrast, dynamic contrast enhancement imaging, and MR-spectroscopy (MRS) were analyzed. Classification of non-enhancing fluid-attenuation-inversion-recovery (FLAIR) area was performed based on mean diffusivity, cerebral blood volume and flow maps, and further characterized using multiple MRI parameters. Results: The non-enhancing FLAIR lesion area was classified into: vasogenic-edema, characterized by reduced perfusion and increased FLAIR values; or tumor-infiltrative area, characterized by increased perfusion. Tumor-infiltrative area demonstrated a higher malignant pattern on MRS compared to areas of vasogenic-edema. Substantial reductions of the enhanced T{sub 1}-weighted (58 ± 10%) and hyperintense FLAIR (53 ± 9%) lesion volumes were detected mainly during the first weeks of therapy, with a shift to an infiltrative pattern of tumor progression thereafter, as detected by an increase in tumor-infiltrative area in the majority of patients, which correlated with progression-free survival (week 8: r = −0.86, p = 0.003, week 16: r = −0.99, p = 0.001). Conclusion: Characterization of non-enhancing hyperintense FLAIR lesion area in GB patients can provide an MR-based biomarker, indicating a shift to an infiltrative progression pattern, and may improve therapy response assessment in patients following bevacizumab therapy.

Observation of reversible, rapid changes in drug susceptibility of hypoxic tumor cells in a microfluidic device

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Germain, Todd; Ansari, Megan; Pappas, Dimitri, E-mail: d.pappas@ttu.edu

2016-09-14

Hypoxia is a major stimulus for increased drug resistance and for survival of tumor cells. Work from our group and others has shown that hypoxia increases resistance to anti-cancer compounds, radiation, and other damage-pathway cytotoxic agents. In this work we utilize a microfluidic culture system capable of rapid switching of local oxygen concentrations to determine changes in drug resistance in prostate cancer cells. We observed rapid adaptation to hypoxia, with drug resistance to 2 μM staurosporine established within 30 min of hypoxia. Annexin-V/Sytox Green apoptosis assays over 9 h showed 78.0% viability, compared to 84.5% viability in control cells (normoxic cells with no staurosporine). Normoxic cells exposed to the same staurosporine concentration had a viability of 48.6% after 9 h. Hypoxia adaptation was rapid and reversible, with Hypoxic cells treated with 20% oxygen for 30 min responding to staurosporine with 51.6% viability after drug treatment for 9 h. Induction of apoptosis through the receptor-mediated pathway, which bypasses anti-apoptosis mechanisms induced by hypoxia, resulted in 39.4 ± 7% cell viability. The rapid reversibility indicates co-treatment of oxygen with anti-cancer compounds may be a potential therapeutic target. - Highlights: • Microfluidic system switches rapidly between normoxia and hypoxia (5 min). • Observation of rapid adaptation of PC3 cells to hypoxia and normoxia (30 min). • Drug susceptibility in tumor cells restored after chip switched to normoxia for 30 min.

Cavitation-enhanced MR-guided focused ultrasound ablation of rabbit tumors in vivo using phase shift nanoemulsions

OpenAIRE

Kopechek, Jonathan A; Park, Eun-Joo; Zhang, Yong-Zhi; Vykhodtseva, Natalia I; McDannold, Nathan J; Porter, Tyrone M

2014-01-01

Advanced tumors are often inoperable due to their size and proximity to critical vascular structures. High intensity focused ultrasound (HIFU) has been developed to non-invasively thermally ablate inoperable solid tumors. However, the clinical feasibility of HIFU ablation therapy has been limited by the long treatment times (on the order of hours) and high acoustic intensities required. Studies have shown that inertial cavitation can enhance HIFU-mediated heating by generating broadband acous...

Degree of Tissue Differentiation Dictates Susceptibility to BRAF-Driven Colorectal Cancer

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Kevin Tong

2017-12-01

Full Text Available Oncogenic mutations in BRAF are believed to initiate serrated colorectal cancers; however, the mechanisms of BRAF-driven colon cancer are unclear. We find that oncogenic BRAF paradoxically suppresses stem cell renewal and instead promotes differentiation. Correspondingly, tumor formation is inefficient in BRAF-driven mouse models of colon cancer. By reducing levels of differentiation via genetic manipulation of either of two distinct differentiation-promoting factors (Smad4 or Cdx2, stem cell activity is restored in BRAFV600E intestines, and the oncogenic capacity of BRAFV600E is amplified. In human patients, we observe that reduced levels of differentiation in normal tissue is associated with increased susceptibility to serrated colon tumors. Together, these findings help resolve the conditions necessary for BRAF-driven colon cancer initiation. Additionally, our results predict that genetic and/or environmental factors that reduce tissue differentiation will increase susceptibility to serrated colon cancer. These findings offer an opportunity to identify susceptible individuals by assessing their tissue-differentiation status.

Doxorubicin-modified magnetic nanoparticles as a drug delivery system for magnetic resonance imaging-monitoring magnet-enhancing tumor chemotherapy.

Science.gov (United States)

Liang, Po-Chin; Chen, Yung-Chu; Chiang, Chi-Feng; Mo, Lein-Ray; Wei, Shwu-Yuan; Hsieh, Wen-Yuan; Lin, Win-Li

2016-01-01

In this study, we developed functionalized superparamagnetic iron oxide (SPIO) nanoparticles consisting of a magnetic Fe3O4 core and a shell of aqueous stable polyethylene glycol (PEG) conjugated with doxorubicin (Dox) (SPIO-PEG-D) for tumor magnetic resonance imaging (MRI) enhancement and chemotherapy. The size of SPIO nanoparticles was ~10 nm, which was visualized by transmission electron microscope. The hysteresis curve, generated with vibrating-sample magnetometer, showed that SPIO-PEG-D was superparamagnetic with an insignificant hysteresis. The transverse relaxivity (r 2) for SPIO-PEG-D was significantly higher than the longitudinal relaxivity (r 1) (r 2/r 1 >10). The half-life of Dox in blood circulation was prolonged by conjugating Dox on the surface of SPIO with PEG to reduce its degradation. The in vitro experiment showed that SPIO-PEG-D could cause DNA crosslink more serious, resulting in a lower DNA expression and a higher cell apoptosis for HT-29 cancer cells. The Prussian blue staining study showed that the tumors treated with SPIO-PEG-D under a magnetic field had a much higher intratumoral iron density than the tumors treated with SPIO-PEG-D alone. The in vivo MRI study showed that the T2-weighted signal enhancement was stronger for the group under a magnetic field, indicating that it had a better accumulation of SPIO-PEG-D in tumor tissues. In the anticancer efficiency study for SPIO-PEG-D, the results showed that there was a significantly smaller tumor size for the group with a magnetic field than the group without. The in vivo experiments also showed that this drug delivery system combined with a local magnetic field could reduce the side effects of cardiotoxicity and hepatotoxicity. The results showed that the developed SPIO-PEG-D nanoparticles own a great potential for MRI-monitoring magnet-enhancing tumor chemotherapy.

Predicting local recurrence following breast-conserving treatment: parenchymal signal enhancement ratio (SER) around the tumor on preoperative MRI

International Nuclear Information System (INIS)

Kim, Mi Young; Cho, Nariya; Koo, Hye Ryoung; Yun, Bo La; Bae, Min Sun; Moon, Woo Kyung; Chie, Eui Kyu

2013-01-01

Background: The level of background parenchymal enhancement around tumor is known to be associated with breast cancer risk. However, there is no study investigating predictive power of parenchymal signal enhancement ratio (SER) around tumor for ipsilateral breast tumor recurrence (IBTR). Purpose: To investigate whether the breast parenchymal SER around the tumor on preoperative dynamic contrast-enhanced magnetic resonance imaging (MRI) is associated with subsequent IBTR in breast cancer patients who had undergone breast-conserving treatment. Material and Methods: Nineteen consecutive women (mean age, 44 years; range, 34-63 years) with breast cancer who developed IBTR following breast-conserving treatment and 114 control women matched for age, as well as T and N stages were included. We compared the clinicopathologic features of the two groups including nuclear grade, histologic grade, hormonal receptor status, human epidermal growth factor receptor-2 (HER-2) status, lymphovascular invasion, negative margin width, use of adjuvant therapy, and parenchymal SER around the tumor on preoperative DCE-MRI. The SER was measured on a slice showing the largest dimension of the tumor. Multivariate conditional logistic regression analysis was used to identify independent factors associated with IBTR. Results: In univariate analysis, ER negativity (odds ratio [OR] = 4.7; P = 0.040), PR negativity (OR = 4.0; P = 0.013), HER-2 positivity (OR = 3.6; P = 0.026), and a parenchymal SER greater than 0.53 (OR = 23.3; P = 0.011) were associated with IBTR. In multivariate analysis, ER negativity (OR = 3.8; P = 0.015) and a parenchymal SER greater than 0.53 (OR = 13.2; P = 0.040) on preoperative MRI were independent factors associated with IBTR. Conclusion: In addition to ER negativity, a higher parenchymal SER on preoperative MRI was an independent factor associated with subsequent IBTR in patients with breast cancer who had undergone breast-conserving treatment

High Frequency of Interactions between Lung Cancer Susceptibility Genes in the Mouse : Mapping of Sluc5 to Sluc14

NARCIS (Netherlands)

Fijneman, Remond J.A.; Jansen, Ritsert C.; Valk, Martin A. van der; Demant, Peter

1998-01-01

Although several genes that cause monogenic familial cancer syndromes have been identified, susceptibility to sporadic cancer remains unresolved. Animal experiments have demonstrated multigenic control of tumor susceptibility. Recently, we described four mouse lung cancer susceptibility (Sluc) loci,

Imaging Tumor Necrosis with Ferumoxytol.

Directory of Open Access Journals (Sweden)

Maryam Aghighi

Full Text Available Ultra-small superparamagnetic iron oxide nanoparticles (USPIO are promising contrast agents for magnetic resonance imaging (MRI. USPIO mediated proton relaxation rate enhancement is strongly dependent on compartmentalization of the agent and can vary depending on their intracellular or extracellular location in the tumor microenvironment. We compared the T1- and T2-enhancement pattern of intracellular and extracellular USPIO in mouse models of cancer and pilot data from patients. A better understanding of these MR signal effects will enable non-invasive characterizations of the composition of the tumor microenvironment.Six 4T1 and six MMTV-PyMT mammary tumors were grown in mice and imaged with ferumoxytol-enhanced MRI. R1 relaxation rates were calculated for different tumor types and different tumor areas and compared with histology. The transendothelial leakage rate of ferumoxytol was obtained by our measured relaxivity of ferumoxytol and compared between different tumor types, using a t-test. Additionally, 3 patients with malignant sarcomas were imaged with ferumoxytol-enhanced MRI. T1- and T2-enhancement patterns were compared with histopathology in a descriptive manner as a proof of concept for clinical translation of our observations.4T1 tumors showed central areas of high signal on T1 and low signal on T2 weighted MR images, which corresponded to extracellular nanoparticles in a necrotic core on histopathology. MMTV-PyMT tumors showed little change on T1 but decreased signal on T2 weighted images, which correlated to compartmentalized nanoparticles in tumor associated macrophages. Only 4T1 tumors demonstrated significantly increased R1 relaxation rates of the tumor core compared to the tumor periphery (p<0.001. Transendothelial USPIO leakage was significantly higher for 4T1 tumors (3.4±0.9x10-3 mL/min/100cm3 compared to MMTV-PyMT tumors (1.0±0.9x10-3 mL/min/100 cm3. Likewise, ferumoxytol imaging in patients showed similar findings with

Repetitive immunization enhances the susceptibility of mice to peripherally administered prions.

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Juliane Bremer

Full Text Available The susceptibility of humans and animals to prion infections is determined by the virulence of the infectious agent, by genetic modifiers, and by hitherto unknown host and environmental risk factors. While little is known about the latter two, the activation state of the immune system was surmised to influence prion susceptibility. Here we administered prions to mice that were repeatedly immunized by two initial injections of CpG oligodeoxynucleotides followed by repeated injections of bovine serum albumin/alum. Immunization greatly reduced the required dosage of peripherally administered prion inoculum necessary to induce scrapie in 50% of mice. No difference in susceptibility was observed following intracerebral prion challenge. Due to its profound impact onto scrapie susceptibility, the host immune status may determine disease penetrance after low-dose prion exposure, including those that may give rise to iatrogenic and variant Creutzfeldt-Jakob disease.

Analyses of susceptibility to radiation-induced tumors: Prkdc, a candidate modifier of lymphomas

International Nuclear Information System (INIS)

Mori, Nobuko; Okumoto, Masaaki; Nakao, Ren

2003-01-01

BALB/cHeA (BALB/c) mice are susceptible to radiation-induced lymphomas, while STS/A (STS) mice are resistant. To analyze the difference in susceptibility between these two strains of mice, we have performed 3 independent studies: 1) mapping of apoptosis susceptibility gene Rapopl (chromosome 16) and identification of Prkdc as a candidate modifier of apoptosis as well as lymphomas, 2) analysis of congenic lines for Lyr, a gene responsible for the lymphoma resistance of STS mice on chromosome 4, 3) genetic analyses of lymphoma susceptibility using a backcross [(BALB/c x STS)F 1 x STS]. Analysis of Rapopl congenic lines indicated a minor contribution of the STS allele at the Rapopl (Prkdc) locus to the lymphoma resistance of STS mice. On the other hand, homozygous STS alleles at Lyr had a substantial, but less potent, effect on radiation lymphomagenesis. Furthermore, there was no single marker where the potent resistance of the STS mice was achieved with the homozygous STS alleles. These results suggest potential involvement of another loci in the resistance of STS mice. (author)

Co-delivery of antigen and IL-12 by Venezuelan equine encephalitis virus replicon particles enhances antigen-specific immune responses and anti-tumor effects

Science.gov (United States)

Osada, Takuya; Berglund, Peter; Morse, Michael A.; Hubby, Bolyn; Lewis, Whitney; Niedzwiecki, Donna; Hobeika, Amy; Burnett, Bruce; Devi, Gayathri R.; Clay, Timothy M.; Smith, Jonathan; Lyerly, H. Kim

2013-01-01

We recently demonstrated that Venezuelan equine encephalitis (VEE) virus-based replicon particles (VRP) encoding tumor antigens could break tolerance in the immunomodulatory environment of advanced cancer. We hypothesized that local injection of VRP expressing Interleukin-12 (IL-12) at the site of injections of VRP-based cancer vaccines would enhance the tumor-antigen-specific T cell and antibody responses and anti-tumor efficacy. Mice were immunized with VRP encoding the human tumor-associated antigen, carcinoembryonic antigen (CEA) (VRP-CEA(6D)) and VRP-IL-12 was also administered at the same site or at a distant location. CEA-specific T cell and antibody responses were measured. To determine antitumor activity, mice were implanted with MC38-CEA-2 cells and immunized with VRP-CEA with and without VRP-IL-12 and tumor growth and mouse survival were measured. VRP-IL-12 greatly enhanced CEA-specific T cell and antibody responses when combined with VRP-CEA(6D) vaccination. VRP IL-12 was superior to IL-12 protein at enhancing immune responses. Vaccination with VRP-CEA(6D) plus VRP-IL-12 was superior to VRP-CEA(6D) or VRP-IL-12 alone in inducing anti-tumor activity and prolonging survival in tumor-bearing mice. Importantly, local injection of VRP-IL-12 at the VRP-CEA(6D) injection site provided more potent activation of CEA-specific immune responses than VRP-IL-12 injected at a distant site from the VRP-CEA injections. Together, this study shows that VRP-IL-12 enhances vaccination with VRP-CEA(6D) and was more effective at activating CEA-specific T cell responses when locally expressed at the vaccine site. Clinical trials evaluating the adjuvant effect of VRP-IL-12 at enhancing the immunogenicity of cancer vaccines are warranted. PMID:22488274

Hemocoagulase Combined with Microbubble-Enhanced Ultrasound Cavitation for Augmented Ablation of Microvasculature in Rabbit VX2 Liver Tumors.

Science.gov (United States)

Yang, Qian; Tang, Peng; He, Guangbin; Ge, Shuping; Liu, Liwen; Zhou, Xiaodong

2017-08-01

We investigated a new method for combining microbubble-enhanced ultrasound cavitation (MEUC) with hemocoagulase (HC) atrox. Our goal was to induce embolic effects in the vasculature and combine these with an anti-angiogenic treatment strategy. Fourteen days after being implanted with a single slice of the liver VX2 tumor, rabbits were randomly divided into five groups: (i) a control group injected intra-venously with saline using a micropump; (ii) a group given only an injection of HC; (iii) a group treated only with ultrasound cavitation; (iv) a group treated with MEUC; (v) a group treated with MEUC + HC. Contrast-enhanced ultrasound was performed before treatment and 1 h and 7 d post-treatment to measure tumor size, enhancement and necrosis range. QontraXt software was used to determine the time-intensity curve of tumor blood perfusion and microvascular changes. At 1 h and 7 d after treatment with MEUC + HC, the parameters of the time-intensity curve, which included peak value, regional blood volume, regional blood flow and area under the curve value and which were measured using contrast-enhanced ultrasound, were significantly lower than those of the other treatment groups. The MEUC + HC treatment group exhibited significant growth inhibition relative to the ultrasound cavitation only, HC and MEUC treatment groups. No damage was observed in the surrounding normal tissues. These results support the feasibility of reducing the blood perfusion of rabbit VX2 liver tumors using a new method that combines MEUC and HC. Copyright © 2017 World Federation for Ultrasound in Medicine & Biology. All rights reserved.

Effect of tumor volume on the enhancement pattern of parathyroid adenoma on parathyroid four-dimensional CT

Energy Technology Data Exchange (ETDEWEB)

Lee, Eun Kyoung [Seoul National University Medical Research Center, Institute of Radiation Medicine, Seoul (Korea, Republic of); Dongguk University Ilsan Hospital, Department of Radiology, Goyang-si (Korea, Republic of); Yun, Tae Jin; Kim, Ji-hoon; Kang, Koung Mi; Choi, Seung Hong; Sohn, Chul-Ho [Seoul National University Medical Research Center, Institute of Radiation Medicine, Seoul (Korea, Republic of); Seoul National University Hospital, Department of Radiology, Jongno-gu, Seoul (Korea, Republic of); Lee, Kyu Eun; Kim, Su-jin [Seoul National University Hospital, Department of Surgery, Seoul (Korea, Republic of); Won, Jae-Kyung [Seoul National University Hospital, Department of Pathology, Seoul (Korea, Republic of)

2016-05-15

The purpose of this study is to assess the effect of tumor volume on the enhancement pattern of parathyroid adenoma (PTA) on four-dimensional computed tomography (4D-CT). We analyzed the enhancement patterns of PTA on four-phase 4D-CT in 44 patients. Dependency of the changes of Hounsfield unit values (ΔHU) on the tumor volumes and clinical characteristics was evaluated using linear regression analyses. In addition, an unpaired t test was used to compare ΔHU of PTAs between PTA volume ≥1 cm{sup 3} and <1 cm{sup 3}, thyroid gland, and lymph node. PTA volume based on CT was the strongest factor on the ΔHU{sub Pre} {sub to} {sub Arterial} and ΔHU{sub Arterial} {sub to} {sub Venous} and ΔHU{sub Arterial} {sub to} {sub Delayed} (R {sup 2} = 0.34, 0.25, and 0.32, respectively, P < 0.001 for both). PTA ≥1 cm {sup 3} had statistically significant greater enhancement between the unenhanced phase and the arterial phase than PTA <1 cm {sup 3} (mean values ± standard deviations (SDs) of ΔHU{sub Pre} {sub to} {sub Arterial}, 102.7 ± 33.7 and 57.5 ± 28.8, respectively, P < 0.001). PTA ≥1 cm {sup 3} showed an early washout pattern on the venous phase, whereas PTA <1 cm {sup 3} showed a progressive enhancement pattern on the venous phase (mean values ± SDs of ΔHU{sub Arterial} {sub to} {sub Venous}, -13.2 ± 31.6 and 14.4 ± 32.7, respectively; P = 0.009). The enhancement pattern of PTA on 4D-CT is variable with respect to PTA volume based on CT. Therefore, the enhancement pattern of PTA on 4D-CT requires careful interpretation concerning the tumor volume, especially in cases of PTA <1 cm {sup 3}. (orig.)

Inflammation-induced synergetic enhancement of nanoparticle treatments with DOXIL{sup ®} and {sup 90}Y-Lactosome for orthotopic mammary tumor

Energy Technology Data Exchange (ETDEWEB)

Kurihara, Kensuke; Ueda, Motoki [Graduate School of Medicine, Kyoto University, Department of Diagnostic Imaging and Nuclear Medicine (Japan); Hara, Isao [Shimadzu Corporation, Technology Research Laboratory (Japan); Hara, Eri [Kyoto University Hospital, Department of Experimental Therapeutics, Institute for Advancement of Clinical and Translational Science (Japan); Sano, Kohei [Graduate School of Medicine, Kyoto University, Department of Diagnostic Imaging and Nuclear Medicine (Japan); Makino, Akira [University of Fukui, Division of Molecular Imaging, Biomedical Imaging Research Center (Japan); Ozeki, Eiichi [Shimadzu Corporation, Technology Research Laboratory (Japan); Yamamoto, Fumihiko [Tohoku Pharmaceutical University, Department of Radiopharmacy (Japan); Saji, Hideo [Kyoto University, Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences (Japan); Togashi, Kaori [Graduate School of Medicine, Kyoto University, Department of Diagnostic Imaging and Nuclear Medicine (Japan); Kimura, Shunsaku, E-mail: shun@scl.kyoto-u.ac.jp [Kyoto University, Department of Material Chemistry, Graduate School of Engineering (Japan)

2016-05-15

Polymeric micelles (Lactosome) in the size of 20–30 nm were labeled with radionuclides of {sup 111}In ({sup 111}In-DOTA-Lactosome) for SPECT imaging and {sup 90}Y ({sup 90}Y-DOTA-Lactosome) for β-ray irradiation for mammary tumor in mice. The tumor site at the femoral right leg grafted with 4T1 cells was clearly imaged at 24 h after the intravenous injection. Biodistribution revealed that the half-life time of {sup 111}In-DOTA-Lactosome was 11 h, which enabled the nanoparticle selectively accumulated in tumor site due to the enhanced permeability and retention (EPR) effect. The anti-tumor therapeutic effect of {sup 90}Y-DOTA-Lactosome was observed depending on the dose frequency and amount. Under the condition of the percutaneous ethanol injection treatment, the therapeutic effect of {sup 90}Y-DOTA-Lactosome was enhanced due to the super EPR effect. Owing to the super EPR effect, co-administration of {sup 90}Y-DOTA-Lactosome and DOXIL{sup ®} inhibited the tumor growth during 15 days with their administrations.

Imaging of brain tumors

Energy Technology Data Exchange (ETDEWEB)

Gaensler, E H.L. [California Univ., San Francisco, CA (United States). Dept. of Radiology

1996-12-31

The contents are diagnostic approaches, general features of tumors -hydrocephalus, edema, attenuation and/or intensity value, hemorrhage, fat, contrast enhancement, intra-axial supratentorial tumors - tumors of glial origin, oligodendrogliomas, ependymomas, subependymomas, subependymal giant cell astrocytomas, choroid plexus papilloma; midline tumors - colloid cysts, craniopharyngiomas; pineal region tumors and miscellaneous tumors i.e. primary intracerebral lymphoma, primitive neuroectodermal tumors, hemangioblastomas; extraaxial tumors - meningiomas; nerve sheath tumors -schwannomas, epidermoids, dermoids, lipomas, arachnoid cysts; metastatic tumors (8 refs.).

Imaging of brain tumors

International Nuclear Information System (INIS)

Gaensler, E.H.L.

1995-01-01

The contents are diagnostic approaches, general features of tumors -hydrocephalus, edema, attenuation and/or intensity value, hemorrhage, fat, contrast enhancement, intra-axial supratentorial tumors - tumors of glial origin, oligodendrogliomas, ependymomas, subependymomas, subependymal giant cell astrocytomas, choroid plexus papilloma; midline tumors - colloid cysts, craniopharyngiomas; pineal region tumors and miscellaneous tumors i.e. primary intracerebral lymphoma, primitive neuroectodermal tumors, hemangioblastomas; extraaxial tumors - meningiomas; nerve sheath tumors -schwannomas, epidermoids, dermoids, lipomas, arachnoid cysts; metastatic tumors (8 refs.)

Bone Marrow Suppression by c-Kit Blockade Enhances Tumor Growth of Colorectal Metastases through the Action of Stromal Cell-Derived Factor-1

Directory of Open Access Journals (Sweden)

Kathrin Rupertus

2012-01-01

Full Text Available Background. Mobilization of c-Kit+ hematopoietic cells (HCs contributes to tumor vascularization. Whereas survival and proliferation of HCs are regulated by binding of the stem cell factor to its receptor c-Kit, migration of HCs is directed by stromal cell-derived factor (SDF-1. Therefore, targeting migration of HCs provides a promising new strategy of anti-tumor therapy. Methods. BALB/c mice (=16 were pretreated with an anti-c-Kit antibody followed by implantation of CT26.WT-GFP colorectal cancer cells into dorsal skinfold chambers. Animals (=8 additionally received a neutralizing anti-SDF-1 antibody. Animals (=8 treated with a control antibody served as controls. Investigations were performed using intravital fluorescence microscopy, immunohistochemistry, flow cytometry and western blot analysis. Results. Blockade of c-Kit significantly enhanced tumor cell engraftment compared to controls due to stimulation of tumor cell proliferation and invasion without markedly affecting tumor vascularization. C-Kit blockade significantly increased VEGF and CXCR4 expression within the growing tumors. Neutralization of SDF-1 completely antagonized this anti-c-Kit-associated tumor growth by suppression of tumor neovascularization, inhibition of tumor cell proliferation and reduction of muscular infiltration. Conclusion. Our study indicates that bone marrow suppression via anti-c-Kit pretreatment enhances tumor cell engraftment of colorectal metastases due to interaction with the SDF-1/CXCR4 pathway which is involved in HC-mediated tumor angiogenesis.

Cone-Beam Computed Tomography (CBCT) Hepatic Arteriography in Chemoembolization for Hepatocellular Carcinoma: Performance Depicting Tumors and Tumor Feeders

Energy Technology Data Exchange (ETDEWEB)

Lee, In Joon [National Cancer Center, Department of Radiology (Korea, Republic of); Chung, Jin Wook, E-mail: chungjw@snu.ac.kr; Yin, Yong Hu; Kim, Hyo-Cheol; Kim, Young Il; Jae, Hwan Jun; Park, Jae Hyung [Seoul National University College of Medicine, Seoul National University Hospital, Department of Radiology (Korea, Republic of)

2015-10-15

PurposeThis study was designed to analyze retrospectively the performance of cone-beam computed tomography (CBCT) hepatic arteriography in depicting tumors and their feeders and to investigate the related determining factors in chemoembolization for hepatocellular carcinoma (HCC).MethodsEighty-six patients with 142 tumors satisfying the imaging diagnosis criteria of HCC were included in this study. The performance of CBCT hepatic arteriography for chemoembolization per tumor and per patient was evaluated using maximum intensity projection images alone (MIP analysis) or MIP combined with multiplanar reformation images (MIP + MPR analysis) regarding the following three aspects: tumor depiction, confidence of tumor feeder detection, and trackability of tumor feeders. Tumor size, tumor enhancement, tumor location, number of feeders, diaphragmatic motion, portal vein enhancement, and hepatic artery to parenchyma enhancement ratio were regarded as potential determining factors.ResultsTumors were depicted in 125 (88.0 %) and 142 tumors (100 %) on MIP and MIP + MPR analysis, respectively. Imaging performances on MIP and MIP + MPR analysis were good enough to perform subsegmental chemoembolization without additional angiographic investigation in 88 (62.0 %) and 128 tumors (90.1 %) on per-tumor basis and in 43 (50 %) and 73 (84.9 %) on per-patient basis, respectively. Significant determining factors for performance in MIP + MPR analysis on per tumor basis were tumor size (p = 0.030), tumor enhancement (0.005), tumor location (p = 0.001), and diaphragmatic motion (p < 0.001).ConclusionsCBCT hepatic arteriography provided sufficient information for subsegmental chemoembolization by depicting tumors and their feeders in the vast majority of patients. Combined analysis of MIP and MPR images was essential to enhance the performance of CBCT hepatic arteriography.

Computed tomography of liver tumors, 2

International Nuclear Information System (INIS)

Naito, Akira; Fukuoka, Haruhito; Kashiwado, Kouzou; Ichiki, Toshio; Makidono, Yoko

1984-01-01

Differential diagnosis between hepatocellular carcinoma and metastatic hepatic tumor was attempted using dynamic CT scanning. Homogeneous and patchy types were peculiar to hepatocellular carcinoma, and ring-like type to metastatic hepatic tumor. However, with no enhancement, hepatocellular carcinoma could not be denied. Hepatocellular carcinoma was characterized by the enhancement shown on the early stage of dynamic CT. Ring enhancement was not visualized on dynamic CT but visualized on conventional contrast enhanced CT in hepatocellular carcinomas; it was visualized on conventional contrast enhanced CT and on dynamic CT in metastatic hepatic tumors. (Namekawa, K.)

Overexpression of Dimethylarginine Dimethylaminohydrolase Enhances Tumor Hypoxia: An Insight into the Relationship of Hypoxia and Angiogenesis In Vivo

Directory of Open Access Journals (Sweden)

Vassiliki Kostourou

2004-07-01

Full Text Available The oxygenation status of tumors derived from wild-type C6 glioma cells and clone D27 cells overexpressing dimethylarginine dimethylaminohydrolase (DDAH was assessed in vivo using a variety of direct and indirect assays of hypoxia. Clone D27 tumors exhibit a more aggressive and better-vascularized phenotype compared to wild-type C6 gliomas. Immunohistochemical analyses using the 2-nitroimidazole hypoxia marker pimonidazole, fiber optic OxyLite measurements of tumor pO2, and localized 31P magnetic resonance spectroscopy measurements of tumor bioenergetic status and pH clearly demonstrated that the D27 tumors were more hypoxic compared to C6 wild type. In the tumor extracts, only glucose concentrations were significantly lower in the D27 tumors. Elevated Glut-1 expression, a reliable functional marker for hypoxia-inducible factor-1-mediated metabolic adaptation, was observed in the D27 tumors. Together, the data show that overexpression of DDAH results in C6 gliomas that are more hypoxic compared to wild-type tumors, and point strongly to an inverse relationship of tumor oxygenation and angiogenesis in vivo-a concept now being supported by the enhanced understanding of oxygen sensing at the molecular level.

Whole-tumor histogram analysis of the cerebral blood volume map: tumor volume defined by 11C-methionine positron emission tomography image improves the diagnostic accuracy of cerebral glioma grading.

Science.gov (United States)

Wu, Rongli; Watanabe, Yoshiyuki; Arisawa, Atsuko; Takahashi, Hiroto; Tanaka, Hisashi; Fujimoto, Yasunori; Watabe, Tadashi; Isohashi, Kayako; Hatazawa, Jun; Tomiyama, Noriyuki

2017-10-01

This study aimed to compare the tumor volume definition using conventional magnetic resonance (MR) and 11C-methionine positron emission tomography (MET/PET) images in the differentiation of the pre-operative glioma grade by using whole-tumor histogram analysis of normalized cerebral blood volume (nCBV) maps. Thirty-four patients with histopathologically proven primary brain low-grade gliomas (n = 15) and high-grade gliomas (n = 19) underwent pre-operative or pre-biopsy MET/PET, fluid-attenuated inversion recovery, dynamic susceptibility contrast perfusion-weighted magnetic resonance imaging, and contrast-enhanced T1-weighted at 3.0 T. The histogram distribution derived from the nCBV maps was obtained by co-registering the whole tumor volume delineated on conventional MR or MET/PET images, and eight histogram parameters were assessed. The mean nCBV value had the highest AUC value (0.906) based on MET/PET images. Diagnostic accuracy significantly improved when the tumor volume was measured from MET/PET images compared with conventional MR images for the parameters of mean, 50th, and 75th percentile nCBV value (p = 0.0246, 0.0223, and 0.0150, respectively). Whole-tumor histogram analysis of CBV map provides more valuable histogram parameters and increases diagnostic accuracy in the differentiation of pre-operative cerebral gliomas when the tumor volume is derived from MET/PET images.

Immuno-enhancement in tumor-bearing mice induced by whole body X-irradiation with 75 mGy

International Nuclear Information System (INIS)

Zhang Ying; Li Xiuyi; Gong Shouliang; Liu Shuzheng

2000-01-01

Objective: In present study the authors observed the effect of whole body irradiation (WBI) with 75 mGy X-rays on the immune function of tumor-bearing mice. Methods: Lewis lung carcinoma cells were implanted into the right thigh muscle of C57BL/6J mice. Ten days after tumor implantation, the tumor-bearing mice were administrated with 75 mGy X-rays WBI, then the mice were sacrificed 18 h after irradiation to detect the immune parameters including the spontaneous proliferation of thymocytes, the proliferative response of splenocytes to ConA and LPS, the cytotoxic activities of specific cytotoxic lymphocytes (CTL) and natural killer cells (NK), as well as lymphokine activated killer cells (LAK) in spleen. The methods the authors used were 3 H-TdR incorporation or release assay. Results: the immune parameters of exposed tumor-bearing mice were much higher than those of sham-irradiated tumor-bearing mice (P<0.01). Conclusion: These results suggested that low dose radiation (LDR) could enhance the immune function of tumor-bearing mice, which might be of practical significance in the prevention and therapy of cancer

Molecular Signatures of Immune Activation and Epithelial Barrier Remodeling Are Enhanced during the Luteal Phase of the Menstrual Cycle: Implications for HIV Susceptibility.

Science.gov (United States)

Birse, Kenzie; Arnold, Kelly B; Novak, Richard M; McCorrister, Stuart; Shaw, Souradet; Westmacott, Garrett R; Ball, Terry B; Lauffenburger, Douglas A; Burgener, Adam

2015-09-01

The variable infectivity and transmissibility of HIV/SHIV has been recently associated with the menstrual cycle, with particular susceptibility observed during the luteal phase in nonhuman primate models and ex vivo human explant cultures, but the mechanism is poorly understood. Here, we performed an unbiased, mass spectrometry-based proteomic analysis to better understand the mucosal immunological processes underpinning this observed susceptibility to HIV infection. Cervicovaginal lavage samples (n = 19) were collected, characterized as follicular or luteal phase using days since last menstrual period, and analyzed by tandem mass spectrometry. Biological insights from these data were gained using a spectrum of computational methods, including hierarchical clustering, pathway analysis, gene set enrichment analysis, and partial least-squares discriminant analysis with LASSO feature selection. Of the 384 proteins identified, 43 were differentially abundant between phases (P HIV. Recent studies have discovered an enhanced susceptibility to HIV infection during the progesterone-dominant luteal phase of the menstrual cycle. However, the mechanism responsible for this enhanced susceptibility has not yet been determined. Understanding the source of this vulnerability will be important for designing efficacious HIV prevention technologies for women. Furthermore, these findings may also be extrapolated to better understand the impact of exogenous hormone application, such as the use of hormonal contraceptives, on HIV acquisition risk. Hormonal contraceptives are the most widely used contraceptive method in sub-Saharan Africa, the most HIV-burdened area of the world. For this reason, research conducted to better understand how hormones impact host immunity and susceptibility factors important for HIV infection is a global health priority. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Differentiating Tumor Progression from Pseudoprogression in Patients with Glioblastomas Using Diffusion Tensor Imaging and Dynamic Susceptibility Contrast MRI.

Science.gov (United States)

Wang, S; Martinez-Lage, M; Sakai, Y; Chawla, S; Kim, S G; Alonso-Basanta, M; Lustig, R A; Brem, S; Mohan, S; Wolf, R L; Desai, A; Poptani, H

2016-01-01

Early assessment of treatment response is critical in patients with glioblastomas. A combination of DTI and DSC perfusion imaging parameters was evaluated to distinguish glioblastomas with true progression from mixed response and pseudoprogression. Forty-one patients with glioblastomas exhibiting enhancing lesions within 6 months after completion of chemoradiation therapy were retrospectively studied. All patients underwent surgery after MR imaging and were histologically classified as having true progression (>75% tumor), mixed response (25%-75% tumor), or pseudoprogression (<25% tumor). Mean diffusivity, fractional anisotropy, linear anisotropy coefficient, planar anisotropy coefficient, spheric anisotropy coefficient, and maximum relative cerebral blood volume values were measured from the enhancing tissue. A multivariate logistic regression analysis was used to determine the best model for classification of true progression from mixed response or pseudoprogression. Significantly elevated maximum relative cerebral blood volume, fractional anisotropy, linear anisotropy coefficient, and planar anisotropy coefficient and decreased spheric anisotropy coefficient were observed in true progression compared with pseudoprogression (P < .05). There were also significant differences in maximum relative cerebral blood volume, fractional anisotropy, planar anisotropy coefficient, and spheric anisotropy coefficient measurements between mixed response and true progression groups. The best model to distinguish true progression from non-true progression (pseudoprogression and mixed) consisted of fractional anisotropy, linear anisotropy coefficient, and maximum relative cerebral blood volume, resulting in an area under the curve of 0.905. This model also differentiated true progression from mixed response with an area under the curve of 0.901. A combination of fractional anisotropy and maximum relative cerebral blood volume differentiated pseudoprogression from

Genetic mapping in mice identifies DMBT1 as a candidate modifier of mammary tumors and breast cancer risk

DEFF Research Database (Denmark)

Blackburn, Anneke C; Hill, Linda Z; Roberts, Amy L

2007-01-01

Low-penetrance breast cancer susceptibility alleles seem to play a significant role in breast cancer risk but are difficult to identify in human cohorts. A genetic screen of 176 N2 backcross progeny of two Trp53(+/-) strains, BALB/c and C57BL/6, which differ in their susceptibility to mammary...... tumors, identified a modifier of mammary tumor susceptibility in an approximately 25-Mb interval on mouse chromosome 7 (designated SuprMam1). Relative to heterozygotes, homozygosity for BALB/c alleles of SuprMam1 significantly decreased mammary tumor latency from 70.7 to 61.1 weeks and increased risk...

Gold nanoparticle-aided brachytherapy with vascular dose painting: estimation of dose enhancement to the tumor endothelial cell nucleus.

Science.gov (United States)

Ngwa, Wilfred; Makrigiorgos, G Mike; Berbeco, Ross I

2012-01-01

Theoretical microdosimetry at the subcellular level is employed in this study to estimate the dose enhancement to tumor endothelial cell nuclei, caused by radiation-induced photo/Auger electrons originating from gold nanoparticles (AuNPs) targeting the tumor endothelium, during brachytherapy. A tumor vascular endothelial cell (EC) is modeled as a slab of 2 μm (thickness) × 10 μm (length) × 10 μm (width). The EC contains a nucleus of 5 μm diameter and thickness of 0.5-1 μm, corresponding to nucleus size 5%-10% of cellular volume, respectively. Analytic calculations based on the electron energy loss formula of Cole were carried out to estimate the dose enhancement to the nucleus caused by photo/Auger electrons from AuNPs attached to the exterior surface of the EC. The nucleus dose enhancement factor (nDEF), representing the ratio of the dose to the nucleus with and without the presence of gold nanoparticles was calculated for different AuNP local concentrations. The investigated concentration range considers the potential for significantly higher local concentration near the EC due to preferential accumulation of AuNP in the tumor vasculature. Four brachytherapy sources: I-125, Pd-103, Yb-169, and 50 kVp x-rays were investigated. For nucleus size of 10% of the cellular volume and AuNP concentrations ranging from 7 to 140 mg/g, brachytherapy sources Pd-103, I-125, 50 kVp, and Yb-169 yielded nDEF values of 5.6-73, 4.8-58.3, 4.7-56.6, and 3.2-25.8, respectively. Meanwhile, for nucleus size 5% of the cellular volume in the same concentration range, Pd-103, I-125, 50 kVp, and Yb-169 yielded nDEF values of 6.9-79.2, 5.1-63.2, 5.0-61.5, and 3.3-28.3, respectively. The results predict that a substantial dose boost to the nucleus of endothelial cells can be achieved by applying tumor vasculature-targeted AuNPs in combination with brachytherapy. Such vascular dose boosts could induce tumor vascular shutdown, prompting extensive tumor cell death.

Gold nanoparticle-aided brachytherapy with vascular dose painting: Estimation of dose enhancement to the tumor endothelial cell nucleus

Energy Technology Data Exchange (ETDEWEB)

Ngwa, Wilfred; Makrigiorgos, G. Mike; Berbeco, Ross I. [Department of Radiation Oncology, Division of Medical Physics and Biophysics, Brigham and Women' s Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115 (United States)

2012-01-15

Purpose: Theoretical microdosimetry at the subcellular level is employed in this study to estimate the dose enhancement to tumor endothelial cell nuclei, caused by radiation-induced photo/Auger electrons originating from gold nanoparticles (AuNPs) targeting the tumor endothelium, during brachytherapy. Methods: A tumor vascular endothelial cell (EC) is modeled as a slab of 2 {mu}m (thickness) x 10 {mu}m (length) x 10 {mu}m (width). The EC contains a nucleus of 5 {mu}m diameter and thickness of 0.5-1 {mu}m, corresponding to nucleus size 5%-10% of cellular volume, respectively. Analytic calculations based on the electron energy loss formula of Cole were carried out to estimate the dose enhancement to the nucleus caused by photo/Auger electrons from AuNPs attached to the exterior surface of the EC. The nucleus dose enhancement factor (nDEF), representing the ratio of the dose to the nucleus with and without the presence of gold nanoparticles was calculated for different AuNP local concentrations. The investigated concentration range considers the potential for significantly higher local concentration near the EC due to preferential accumulation of AuNP in the tumor vasculature. Four brachytherapy sources: I-125, Pd-103, Yb-169, and 50 kVp x-rays were investigated. Results: For nucleus size of 10% of the cellular volume and AuNP concentrations ranging from 7 to 140 mg/g, brachytherapy sources Pd-103, I-125, 50 kVp, and Yb-169 yielded nDEF values of 5.6-73, 4.8-58.3, 4.7-56.6, and 3.2-25.8, respectively. Meanwhile, for nucleus size 5% of the cellular volume in the same concentration range, Pd-103, I-125, 50 kVp, and Yb-169 yielded nDEF values of 6.9-79.2, 5.1-63.2, 5.0-61.5, and 3.3-28.3, respectively. Conclusions: The results predict that a substantial dose boost to the nucleus of endothelial cells can be achieved by applying tumor vasculature-targeted AuNPs in combination with brachytherapy. Such vascular dose boosts could induce tumor vascular shutdown, prompting

Expression of PD-L1 on canine tumor cells and enhancement of IFN-γ production from tumor-infiltrating cells by PD-L1 blockade.

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Naoya Maekawa

Full Text Available Programmed death 1 (PD-1, an immunoinhibitory receptor, and programmed death ligand 1 (PD-L1, its ligand, together induce the "exhausted" status in antigen-specific lymphocytes and are thus involved in the immune evasion of tumor cells. In this study, canine PD-1 and PD-L1 were molecularly characterized, and their potential as therapeutic targets for canine tumors was discussed. The canine PD-1 and PD-L1 genes were conserved among canine breeds. Based on the sequence information obtained, the recombinant canine PD-1 and PD-L1 proteins were constructed; they were confirmed to bind each other. Antibovine PD-L1 monoclonal antibody effectively blocked the binding of recombinant PD-1 with PD-L1-expressing cells in a dose-dependent manner. Canine melanoma, mastocytoma, renal cell carcinoma, and other types of tumors examined expressed PD-L1, whereas some did not. Interestingly, anti-PD-L1 antibody treatment enhanced IFN-γ production from tumor-infiltrating cells. These results showed that the canine PD-1/PD-L1 pathway is also associated with T-cell exhaustion in canine tumors and that its blockade with antibody could be a new therapeutic strategy for canine tumors. Further investigations are needed to confirm the ability of anti-PD-L1 antibody to reactivate canine antitumor immunity in vivo, and its therapeutic potential has to be further discussed.

Tumor vascularity of experimentally induced VX2 carcinoma in the rabbit thigh: evaluation with enhanced power doppler sonography and DSA correlated with histopathologic findings

Energy Technology Data Exchange (ETDEWEB)

Kim, Young Hoon; Han, Joon Koo; Chung, Jin Wook; Lee, Kyoung Ho; Kim, Se Hyung; Kim, Seog Joon; Choi, Byung Ihn; Chang, Kee Hyun [College of Medicine, Seoul National Univ., Seoul (Korea, Republic of)

2002-05-01

To describe findings of enhanced power Doppler sonography and DSA in experimentally induced VX2 carcinomas in rabbit thigh and to correlate the imaging findings with the histopathologic features. A total of 30 VX2 carcinomas were implanted in rabbit thigh, and after conventional and enhanced power Doppler sonography and DSA, histopathologic examination was performed. Enhanced power Doppler sonography and DSA, were used to determine the distribution pattern of tumor vascularity; to assess its grade and the percentage of a tumor area occupied by vessels, conventional and enhanced power Doppler sonography, as well as DSA, were used. The grade of necrosis and the development of fibrovascular stroma and capsule were histopathologically determined. The findings of power Doppler sonography were compared with those of DSA and the imaging features were correlated with the histopathologic features. At enhanced power Doppler sonography, the signal was either avascular (n=9), peripheral (n=15) or diffuse (n=6), while at DSA, the corresponding totals were eight, fourteen and eight. There was statistically significant corelation between enhanced power Doppler sonogrpahy and DSA, both in their depiction of the distribution of patterns of tumor vascularity and as regards their findings of grade and percentage of vascular area. As determined by both conventional and enhanced power Doppler sonogrpahy, and by DSA, grade of necrosis and the development of fibrovascular stroma and a capsule correlated with grade and the percentage of vascular area. Experimentally induced VX2 carcinomas in rabbit thigh demonstrated various patterns of tumor vascularity, and the findings of enhanced power Doppler sonography correlated with those of DSA. Tumor vascularity, as demonstrated by two imaging modalities, correlated closely with grade of necrosis and the development of fibrovascular stroma and a capsule, as revealed by histopathologic examination.

Tumor vascularity of experimentally induced VX2 carcinoma in the rabbit thigh: evaluation with enhanced power doppler sonography and DSA correlated with histopathologic findings

International Nuclear Information System (INIS)

Kim, Young Hoon; Han, Joon Koo; Chung, Jin Wook; Lee, Kyoung Ho; Kim, Se Hyung; Kim, Seog Joon; Choi, Byung Ihn; Chang, Kee Hyun

2002-01-01

To describe findings of enhanced power Doppler sonography and DSA in experimentally induced VX2 carcinomas in rabbit thigh and to correlate the imaging findings with the histopathologic features. A total of 30 VX2 carcinomas were implanted in rabbit thigh, and after conventional and enhanced power Doppler sonography and DSA, histopathologic examination was performed. Enhanced power Doppler sonography and DSA, were used to determine the distribution pattern of tumor vascularity; to assess its grade and the percentage of a tumor area occupied by vessels, conventional and enhanced power Doppler sonography, as well as DSA, were used. The grade of necrosis and the development of fibrovascular stroma and capsule were histopathologically determined. The findings of power Doppler sonography were compared with those of DSA and the imaging features were correlated with the histopathologic features. At enhanced power Doppler sonography, the signal was either avascular (n=9), peripheral (n=15) or diffuse (n=6), while at DSA, the corresponding totals were eight, fourteen and eight. There was statistically significant corelation between enhanced power Doppler sonogrpahy and DSA, both in their depiction of the distribution of patterns of tumor vascularity and as regards their findings of grade and percentage of vascular area. As determined by both conventional and enhanced power Doppler sonogrpahy, and by DSA, grade of necrosis and the development of fibrovascular stroma and a capsule correlated with grade and the percentage of vascular area. Experimentally induced VX2 carcinomas in rabbit thigh demonstrated various patterns of tumor vascularity, and the findings of enhanced power Doppler sonography correlated with those of DSA. Tumor vascularity, as demonstrated by two imaging modalities, correlated closely with grade of necrosis and the development of fibrovascular stroma and a capsule, as revealed by histopathologic examination

MRI diagnosis of tongue tumors

International Nuclear Information System (INIS)

Minowa, Kazuyuki; Abe, Satoru; Ohmori, Keiichi; Hosokawa, Yoichirou; Yamasaki, Michio; Hirano, Masayasu.

1992-01-01

MRI studies were performed on 29 patients with tongue tumors. Twenty-six cases were fresh, others were recurrent. Signal intensity of tongue tumor was not characteristic and specific, and it was a low∼iso signal on T1 weighted image (WI), heterogeneously iso∼high signal intensity on T2 WI, heterogeneous enhancement on gadolinium-DTPA enhanced image compared to muscle signal intensity. In 3 of 29 patients, the tongue tumor invaded to the mandible. With regard to the grasping tumor invasion to the mandible, the STIR method was superior to T1, T2 WI of the spin echo method. Dynamic enhanced MR images were performed in 6 of 29 patients. Dynamic change of signal intensity after gadolinium-DTPA administration were assessed with fast low angle shot imaging. On dynamic study at about 20 seconds after gadolinium-DTPA injection, the first signal intensity in the periphery of the tumor gradually began to increase. Maximum signal intensity of the tumor showed at about 70 seconds after gadolinium-DTPA injection. In search from 0 to 5 minutes, after the tongue tumor showed maximum signal intensity, its signal maintain the maximum. Necrotic and peritumorous edema showed a significantly lower and more gradual increase in signal intensity than adjacent neoplastic tissue on dynamic enhanced MRI. (author)

Renal Tumors: Technical Success and Early Clinical Experience with Radiofrequency Ablation of 18 Tumors

International Nuclear Information System (INIS)

Sabharwal, Rohan; Vladica, Philip

2006-01-01

Purpose. To evaluate the feasibility, safety, and technical efficacy of image-guided radiofrequency ablation (RFA) for the treatment of small peripheral renal tumors and to report our early results with this treatment modality. Methods. Twenty-two RFA sessions for 18 tumors were performed in 11 patients with renal tumors. Indications included coexistent morbidity, high surgical or anesthetic risk, solitary kidney, and hereditary predisposition to renal cell carcinoma. Ten patients had CT-guided percutaneous RFA performed on an outpatient basis. One patient had open intraoperative ultrasound-guided RFA. Technical success was defined as elimination of areas that enhanced at imaging within the entire tumor. With the exception of one patient with renal insufficiency who required gadolinium-enhanced MRI, the remaining patients underwent contrast-enhanced CT for post-treatment follow-up assessment. Follow-up was performed after 2-4 weeks and then at 3, 6, 12 months, and every 12 months thereafter. Results. Fourteen (78%) of 18 tumors were successfully ablated with one session. Three of the remaining four tumors required two sessions for successful ablation. One tumor will require a third session for areas of persistent enhancement. Mean patient age was 72.82 ± 10.43 years. Mean tumor size was 1.95 ± 0.79 cm. Mean follow-up time was 10.91 months. All procedures were performed without any major complications. Conclusions. Our early experience with percutaneous image-guided radiofrequency ablation demonstrates it to be a feasible, safe, noninvasive, and effective treatment of small peripheral renal tumors

Breast tumor size assessment: comparison of conventional ultrasound and contrast-enhanced ultrasound.

Science.gov (United States)

Jiang, Yu-Xin; Liu, He; Liu, Ji-Bin; Zhu, Qing-Li; Sun, Qiang; Chang, Xiao-Yan

2007-12-01

Accurate assessment of tumor size is necessary when selecting patients for breast-conserving surgery. In the study of breast contrast-enhanced ultrasound (CEUS), we found that tumor size discrepancy between CEUS and conventional ultrasound (US) existed in some breast lesions, for which the reasons are not clear. Breast CEUS examinations were performed in 104 patients with breast lesions. The measurement of the 104 breast tumors on conventional US was obtained and compared with the measurement on CEUS. A difference in measuring tumor size of >3 mm for tumors up to 1.7 cm and 4 mm for tumors >or=1.7 cm, was defined as a significant discrepancy between conventional US and CEUS. The histopathological examination of size discrepancy was performed and the margin characteristics of breast cancers with larger measurements were compared with those with unchanged measurements. Among the 104 lesions (43 malignant, 60 benign, 1 borderline), the size of 27 breast cancers and one granulomatous mastitis appeared larger at CEUS. Pathologic examinations of the region corresponding to the measurement discrepancy were mainly ductal carcinomas in situ (DCIS), invasive carcinoma with a DCIS component, adenosis with lobular hyperplasia in breast cancers and inflammatory cell infiltration in one granulomatous mastitis. Well-defined margin characteristics were significantly different between breast cancers with larger measurements at CEUS and those with unchanged measurements of size (p = 0.002), whereas no significant difference was found between the two groups in ill-defined, spiculated, hyperechoic halo, microlobulated and angulated margins (p = 0.463, 0.117, 0.194, 0.666 and 0.780, respectively). This initial study suggests that significant discrepancy of breast lesion measurement between conventional US and CEUS is more likely presented in breast cancer than benign lesions. The pathologic findings corresponding to the region of size increased at CEUS are malignant in most malignant

High contrast enhancement aspect of dynamic computed tomography with arterial infusion - DCT-AI. Its clinical applications on hepatic tumors and basic experiments

Energy Technology Data Exchange (ETDEWEB)

Kato, Seishi; Iwasaki, Naoya; Matsumura, Yoshimitsu; Kuramae, Shigeru; Mishiro, Tadashi

1983-06-01

Dynamic computed tomography was performed on 112 cases possibly having hepatic tumors with intraarterial infusion of undiluted contrast into a selectively placed catheter following angiographies. Our dynamic program could evaluate not only early phase of enhancement but also late phase up to 120 sec. Reconstructed views from early scans and magnified views were very useful to evaluate minute sequential changes. Hepatic masses less than 5 cm in size were found in thirty-one cases. Patterns of tumor enhancement and time-density curves have been analysed to correlate them with histology. Four types of tumor enhancement were noted: (1) homogeneous (2) patchy (3) mottled (4) ringed. Characteristic changes were observed in hepatocellular carcinoma - HCC - (mostly mottled) and haemangioma (mostly patchy). The former was divided in two groups reflecting the cellular maturity. The metastatic tumor could be enhanced in a ringed form with dendritic pattern of supplying vascularities in some cases. To support the use of undiluted contrast and to investigate the diagnostic efficacy of high contrast enhancement, experiments were performed by taking transaxial views of an acrylic phantom immersed in different concentrations of contrast. Analysis of CT images taken at different HU values ranging from 0 to 450 demonstrated that the higher the concentration of contrast, the better the spatial resolution was. Also larger magnification could be expected by using higher concentration of contrast. Although our Dynamic Computed Tomography with Arterial Infusion of Contrast still has drawbacks and limited indications, we advocate it as a better way of enhancement to detect and evaluate the hepatic masses, which sometimes elude the examiner's grasp with conventional way of enhancement. (author).

Enhanced Dentate Neurogenesis after Brain Injury Undermines Long-Term Neurogenic Potential and Promotes Seizure Susceptibility

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Eric J. Neuberger

2017-09-01

Full Text Available Hippocampal dentate gyrus is a focus of enhanced neurogenesis and excitability after traumatic brain injury. Increased neurogenesis has been proposed to aid repair of the injured network. Our data show that an early increase in neurogenesis after fluid percussion concussive brain injury is transient and is followed by a persistent decrease compared with age-matched controls. Post-injury changes in neurogenesis paralleled changes in neural precursor cell proliferation and resulted in a long-term decline in neurogenic capacity. Targeted pharmacology to restore post-injury neurogenesis to control levels reversed the long-term decline in neurogenic capacity. Limiting post-injury neurogenesis reduced early increases in dentate excitability and seizure susceptibility. Our results challenge the assumption that increased neurogenesis after brain injury is beneficial and show that early post-traumatic increases in neurogenesis adversely affect long-term outcomes by exhausting neurogenic potential and enhancing epileptogenesis. Treatments aimed at limiting excessive neurogenesis can potentially restore neuroproliferative capacity and limit epilepsy after brain injury.

Targeted gadolinium-loaded dendrimer nanoparticles for tumor-specific magnetic resonance contrast enhancement

Directory of Open Access Journals (Sweden)

Scott D Swanson

2008-06-01

Full Text Available Scott D Swanson1, Jolanta F Kukowska-Latallo2, Anil K Patri5, Chunyan Chen6, Song Ge4, Zhengyi Cao3, Alina Kotlyar3, Andrea T East7, James R Baker31Department of Radiology, The University of Michigan Medical School, 2Department of Internal Medicine, The University of Michigan Medical School, 3Michigan Nanotechnology Institute for Medicine and Biological Sciences, The University of Michigan, 4Applied Physics, The University of Michigan, MD, USA; 5Present address: National Cancer Institute at Frederick (Contractor, MD, USA; 6Present address: Intel Corporation, Chandler, AZ, USA; 7Present address: Stritch School of Medicine, Chicago, ILL, USAAbstract: A target-specific MRI contrast agent for tumor cells expressing high affinity folate receptor was synthesized using generation five (G5 of polyamidoamine (PAMAM dendrimer. Surface modified dendrimer was functionalized for targeting with folic acid (FA and the remaining terminal primary amines of the dendrimer were conjugated with the bifunctional NCS-DOTA chelator that forms stable complexes with gadolinium (Gd III. Dendrimer-DOTA conjugates were then complexed with GdCl3, followed by ICP-OES as well as MRI measurement of their longitudinal relaxivity (T1 s−1 mM−1 of water. In xenograft tumors established in immunodeficient (SCID mice with KB human epithelial cancer cells expressing folate receptor (FAR, the 3D MRI results showed specific and statistically significant signal enhancement in tumors generated with targeted Gd(III-DOTA-G5-FA compared with signal generated by non-targeted Gd(III-DOTA-G5 contrast nanoparticle. The targeted dendrimer contrast nanoparticles infiltrated tumor and were retained in tumor cells up to 48 hours post-injection of targeted contrast nanoparticle. The presence of folic acid on the dendrimer resulted in specific delivery of the nanoparticle to tissues and xenograft tumor cells expressing folate receptor in vivo. We present the specificity of the dendrimer

Inhibition or knockdown of ABC transporters enhances susceptibility of adult and juvenile schistosomes to Praziquantel.

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Ravi S Kasinathan

2014-10-01

parasite ABC multidrug transporters might serve as important targets for enhancing the action of PZQ. They also suggest a potentially novel and readily-available strategy for overcoming reduced PZQ susceptibility of schistosomes.

Tumor-Associated Macrophages and Neutrophils in Tumor Microenvironment

Directory of Open Access Journals (Sweden)

Jaehong Kim

2016-01-01

Full Text Available Distinct tumor microenvironment forms in each progression step of cancer and has diverse capacities to induce both adverse and beneficial consequences for tumorigenesis. It is now known that immune cells can be activated to favor tumor growth and progression, most probably influenced by the tumor microenvironment. Tumor-associated macrophages and tumor-associated neutrophils can exert protumoral functions, enhancing tumor cell invasion and metastasis, angiogenesis, and extracellular matrix remodeling, while inhibiting the antitumoral immune surveillance. Considering that neutrophils in inflammatory environments recruit macrophages and that recruited macrophages affect neutrophil functions, there may be various degrees of interaction between tumor-associated macrophages and tumor-associated neutrophils. Platelets also play an important role in the recruitment and regulation of monocytic and granulocytic cells in the tumor tissues, suggesting that platelet function may be essential for generation of tumor-associated macrophages and tumor-associated neutrophils. In this review, we will explore the biology of tumor-associated macrophages and tumor-associated neutrophils and their possible interactions in the tumor microenvironment. Special attention will be given to the recruitment and activation of these tumor-associated cells and to the roles they play in maintenance of the tumor microenvironment and progression of tumors.

Strategies for enhancing adoptive T-cell immunotherapy against solid tumors using engineered cytokine signaling and other modalities.

Science.gov (United States)

Shum, Thomas; Kruse, Robert L; Rooney, Cliona M

2018-05-04

Cancer therapy has been transformed by the demonstration that tumor-specific T-cells can eliminate tumor cells in a clinical setting with minimal long-term toxicity. However, significant success in the treatment of leukemia and lymphoma with T-cells using native receptors or redirected with chimeric antigen receptors (CARs) has not been recapitulated in the treatment of solid tumors. This lack of success is likely related to the paucity of costimulatory and cytokine signaling available in solid tumors, in addition to a range of inhibitory mechanisms. Areas covered: We summarize the latest developments in engineered T-cell immunotherapy, describe the limitations of these approaches in treating solid tumors, and finally highlight several strategies that may be useful in mediating solid tumor responses in the future, while also ensuring safety of engineered cells. Expert opinion: CAR-T therapies require further engineering to achieve their potential against solid tumors. Facilitating cytokine signaling in CAR T-cells appears to be essential in achieving better responses. However, the engineering of T-cells with potentially unchecked proliferation and potency raises the question of whether the simultaneous combination of enhancements will prove safe, necessitating continued advancements in regulating CAR-T activity at the tumor site and methods to safely switch off these engineered cells.

Detection of hepatic VX2 tumors in rabbits: comparison of conventional US and phase- inversion harmonic US during the liver- specific late phase of contrast enhancement

International Nuclear Information System (INIS)

Lee, Jeong Min; Youk, Ji Hyun; Lee, Young Hwan; Kim, Young Kon; Kim, Chong Soo; Li, Chun Ai

2003-01-01

To compare phase-inversion sonography during the liver-specific phase of contrast enhancement using a microbubble contrast agent with conventional B-mode sonography for the detection of VX2 liver tumors. Twenty-three rabbits, 18 of which had VX2 liver tumor implants, received a bolus injection of 0.6 g of Levovist (200 mg/ml). During the liver-specific phase of this agent, they were evaluated using both conventional sonography and contrast-enhanced phase-inversion harmonic imaging (CEPIHI). Following sacrifice of the animals, pathologic analysis was performed and the reference standard thus obtained. The conspicuity, size and number of the tumors before and after contrast administration, as determined by a sonographer, were compared between the two modes and with the pathologic findings. CE-PIHI demonstrated marked hepatic parenchymal enhancement in all rabbits. For VX2 tumors detected at both conventional US and CE- PIHI, conspicuity was improved by contrast-enhanced PIHI. On examination of gross specimens, 52 VX2 tumors were identified. Conventional US correctly detected 18 of the 52 (34.6%), while PIHI detected 35 (67.3%) (p < 0.05). In particular, conventional US detected only three (8.3%) of the 36 tumors less than 10 mm in diameter, but CE-PIHI detected 19 such tumors (52.8%) (p < 0.05). Compared to conventional sonography, PIHI performed during the liver-specific phase after intravenous injection of Levovist is markedly better at detecting VX2 liver tumors

Folic acid-targeted disulfide-based cross-linking micelle for enhanced drug encapsulation stability and site-specific drug delivery against tumors

Directory of Open Access Journals (Sweden)

Zhang Y

2016-03-01

Full Text Available Yumin Zhang,1,* Junhui Zhou,2,* Cuihong Yang,1 Weiwei Wang,3 Liping Chu,1 Fan Huang,1 Qiang Liu,1 Liandong Deng,2 Deling Kong,3 Jianfeng Liu,1 Jinjian Liu1 1Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science and Peking Union Medical College, 2Department of Polymer Science and Technology, School of Chemical Engineering and Technology, Tianjin University, 3Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, People’s Republic of China *These authors contributed equally in this work Abstract: Although the shortcomings of small molecular antitumor drugs were efficiently improved by being entrapped into nanosized vehicles, premature drug release and insufficient tumor targeting demand innovative approaches that boost the stability and tumor responsiveness of drug-loaded nanocarriers. Here, we show the use of the core cross-linking method to generate a micelle with enhanced drug encapsulation ability and sensitivity of drug release in tumor. This kind of micelle could increase curcumin (Cur delivery to HeLa cells in vitro and improve tumor accumulation in vivo. We designed and synthesized the core cross-linked micelle (CCM with polyethylene glycol and folic acid-polyethylene glycol as the hydrophilic units, pyridyldisulfide as the cross-linkable and hydrophobic unit, and disulfide bond as the cross-linker. CCM showed spherical shape with a diameter of 91.2 nm by the characterization of dynamic light scattering and transmission electron microscope. Attributed to the core cross-linking, drug-loaded CCM displayed higher Nile Red or Cur-encapsulated stability and better sensitivity to glutathione than noncross-linked micelle (NCM. Cellular uptake and in vitro antitumor studies proved the enhanced endocytosis and better cytotoxicity of CCM-Cur against

Radionecrosis after radiotherapy for brain tumor

International Nuclear Information System (INIS)

Yoshii, Yoshihiko; Maki, Yutaka; Tosa, Junichi; Tsuboi, Koji; Matsumura, Akira

1984-01-01

The neurological deterioration after radiotherapy of brain tumor may depend on radionecrosis or regrowth of the tumor. In the present study, five patients with brain tumor were irradiated with doses of 3,900 to 6,800 rads. The neurological deterioration appeared 3.5 to 46 months after radiotherapy in three patients, who received 5,000 to 5,680 rads, immediately after radiotherapy in one patient, who received 6,800 rads, and during radiotherapy in one patient, who received 3,900 rads. Ring enhancement was observed on sequential CT scans. This enhanced area was surgically removed and the correlation between histology and CT scans and superimposed dose distributions was studied in order to differentiate radionecrosis from regrowth of tumor. The radionecrosis was confirmed at the second operation in five patients, but regrowth of the tumor was also observed in the brain adjacent to radionecrosis in three out of five patients. Coagulation necrosis and fibrinoid necrosis were observed microscopically at the rim of the ring enhancement and necrotic and hyalinized debri were observed in the central low density area of the ring enhancement. Viable tumor cells were noted in the enhanced area adjacent to the ring enhancement on CT scans. Both radionecrosis and regrowth of tumor were observed in the dose distribution area of 3,500 to 6,120 rads on CT scans. This suggested that the superimposed dose distributions could not differentiate radionecrosis from tumor regrowth. Forty-eight cases of cerebral radionecrosis gathered from the literature were reviewed. (J.P.N.)

Inhibition of human esophageal squamous cell carcinomas by targeted silencing of tumor enhancer genes: an overview

International Nuclear Information System (INIS)

Islamian, Jalil Pirayesh; Mohammadi, Mohsen; Baradaran, Behzad

2014-01-01

Esophageal cancer has been reported as the ninth most common malignancy and ranks as the sixth most frequent cause of death worldwide. Esophageal cancer treatment involves surgery, chemotherapy, radiation therapy, or combination therapy. Novel strategies are needed to boost the oncologic outcome. Recent advances in the molecular biology of esophageal cancer have documented the role of genetic alterations in tumorigenesis. Oncogenes serve a pivotal function in tumorigenesis. Targeted therapies are directed at the unique molecular signature of cancer cells for enhanced efficacy with low toxicity. RNA interference (RNAi) technology is a powerful tool for silencing endogenous or exogenous genes in mammalian cells. Related results have shown that targeting oncogenes with siRNAs, specifically the mRNA, effectively reduces tumor cell proliferation and induces apoptotic cell death. This article will briefly review studies on silencing tumor enhancer genes related to the induction of esophageal cancer

The CDK4/6 Inhibitor Abemaciclib Induces a T Cell Inflamed Tumor Microenvironment and Enhances the Efficacy of PD-L1 Checkpoint Blockade

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David A. Schaer

2018-03-01

Full Text Available Summary: Abemaciclib, an inhibitor of cyclin dependent kinases 4 and 6 (CDK4/6, has recently been approved for the treatment of hormone receptor-positive breast cancer. In this study, we use murine syngeneic tumor models and in vitro assays to investigate the impact of abemaciclib on T cells, the tumor immune microenvironment and the ability to combine with anti-PD-L1 blockade. Abemaciclib monotherapy resulted in tumor growth delay that was associated with an increased T cell inflammatory signature in tumors. Combination with anti-PD-L1 therapy led to complete tumor regressions and immunological memory, accompanied by enhanced antigen presentation, a T cell inflamed phenotype, and enhanced cell cycle control. In vitro, treatment with abemaciclib resulted in increased activation of human T cells and upregulated expression of antigen presentation genes in MCF-7 breast cancer cells. These data collectively support the clinical investigation of the combination of abemaciclib with agents such as anti-PD-L1 that modulate T cell anti-tumor immunity. : Schaer, Beckmann et al. describe unique immune-modulating properties of abemaciclib that include upregulation of antigen presentation on tumor cells and increased T cell activation. These activities synergize with anti-PD-L1 therapy to further enhance immune activation, including macrophage and DC antigen presentation, and also lead to a reciprocal increase in abemaciclib-dependent cell cycle gene regulation. Keywords: CDK4/6, abemaciclib, PD-1, PD-L1, combination immunotherapy, cancer

Celecoxib enhances radiation response of secondary bone tumors of a human non-small cell lung cancer via antiangiogenesis in vivo

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Klenke, Frank Michael [Bern Univ. (Switzerland). Dept. of Orthopedic Surgery; Abdollahi, Amir [Deutsches Krebsforschungszentrum, Heidelberg (Germany). Dept. of Radiation Oncology; Tufts Univ. School of Medicine, Boston, MA (United States). Center of Cancer Systems Biology; Bischof, Marc; Huber, Peter E. [Deutsches Krebsforschungszentrum, Heidelberg (Germany). Dept. of Radiation Oncology; Gebhard, Martha-Maria [Heidelberg Univ. (Germany). Dept. of Experimental Surgery; Ewerbeck, Volker [Heidelberg Univ. (Germany). Dept. of Orthopedic Surgery; Sckell, Axel [Charite Univ. Medical Center, Berlin (Germany). Dept. of Orthopedic, Trauma and Reconstructive Surgery

2011-01-15

Purpose: Cyclooxygenase-2 (COX-2) inhibitors mediate a systemic antitumor activity via antiangiogenesis and seem to enhance the response of primary tumors to radiation. Radiosensitizing effects of COX-2 inhibition have not been reported for bone metastases. Therefore, the aim of this study was the investigation of the radiosensitizing effects of the selective COX-2 inhibitor celecoxib in secondary bone tumors of a non-small cell lung carcinoma in vivo. Materials and Methods: Human A549 lung carcinomas were implanted into a cranial window preparation in male SCID mice (n = 24). Animals were treated with either celecoxib or radiation (7 Gy single photon dose) alone or a combination of celecoxib and radiation, respectively. Untreated animals served as controls. The impact of radiation and COX-2 inhibition on angiogenesis, microcirculation, and tumor growth was analyzed over 28 days by means of intravital microscopy and histological methods. Results: Monotherapies with radiation as well as celecoxib had significant antitumor effects compared to untreated controls. Both therapies reduced tumor growth and vascularization to a similar extent. The simultaneous administration of celecoxib and radiation further enhanced the antitumor and antiangiogenic effects of single-beam radiation. With the combined treatment approach, tumor vascularization and tumor size were decreased by 57% and 51%, respectively, as compared to monotherapy with radiation. Conclusion: The combined application of radiation therapy and COX-2 inhibition showed synergistic effects concerning the inhibition of tumor growth and tumor angiogenesis. Therefore, the combination of radiation with COX-2 inhibitor therapy represents a promising approach to improve the therapeutic efficacy of radiotherapy of bone metastases. (orig.)

Intensity and Pattern of Enhancement on CESM: Prognostic Significance and its Relation to Expression of Podoplanin in Tumor Stroma - A Preliminary Report.

Science.gov (United States)

Luczynska, Elzbieta; Niemiec, Joanna; Heinze, Sylwia; Adamczyk, Agnieszka; Ambicka, Aleksandra; Marcyniuk, Paulina; Rudnicki, Wojciech; Mitus, Jerzy W; Dyczek, Sonia; Rys, Janusz; Sas-Korczynska, Beata

2018-02-01

It is possible that the degree of enhancement on contrast-enhanced spectral mammography (CESM), a new diagnostic method, might provide prognostic information for breast cancer patients. Therefore, in a group of 82 breast cancer patients, we analyzed the prognostic significance of degree and pattern of enhancement on CESM as well as its relation to: (a) breast cancer immunophenotype (based on ER/PR/HER2 status) (b) podoplanin expression in cancer stroma (lymphatic vessel density plus podoplanin-positivity of cancer-associated fibroblasts), and (c) other histological parameters. For each tumor the intensity of enhancement on CESM was qualitatively assessed as strong or weak/medium, while the pattern - as homogenous and heterogenous. Herein we report, for the first time, that strong and heterogenous enhancement on CESM was related to unfavorable disease-free survival of breast cancer patients (p=0.005). Moreover, the strong enhancement was more frequent in large and node-positive tumors (pT>1, pN>0) (p=0.002), as well as in carcinomas with podoplanin-sparse stroma (p=0.008). Intensity and pattern of enhancement on CESM might provide (together with the results of other diagnostic imaging methods) not only the confirmation of presence or absence of tumor, but also prognostic information. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Endotoxin/lipopolysaccharide activates NF-kappa B and enhances tumor cell adhesion and invasion through a beta 1 integrin-dependent mechanism.

LENUS (Irish Health Repository)

Wang, Jiang Huai

2012-02-03

Beta(1) integrins play a crucial role in supporting tumor cell attachment to and invasion into the extracellular matrix. Endotoxin\\/LPS introduced by surgery has been shown to enhance tumor metastasis in a murine model. Here we show the direct effect of LPS on tumor cell adhesion and invasion in extracellular matrix proteins through a beta(1) integrin-dependent pathway. The human colorectal tumor cell lines SW480 and SW620 constitutively expressed high levels of the beta(1) subunit, whereas various low levels of alpha(1), alpha(2), alpha(4), and alpha(6) expression were detected. SW480 and SW620 did not express membrane-bound CD14; however, LPS in the presence of soluble CD14 (sCD14) significantly up-regulated beta(1) integrin expression; enhanced tumor cell attachment to fibronectin, collagen I, and laminin; and strongly promoted tumor cell invasion through the Matrigel. Anti-beta(1) blocking mAbs (4B4 and 6S6) abrogated LPS- plus sCD14-induced tumor cell adhesion and invasion. Furthermore, LPS, when combined with sCD14, resulted in NF-kappaB activation in both SW480 and SW620 cells. Inhibition of the NF-kappaB pathway significantly attenuated LPS-induced up-regulation of beta(1) integrin expression and prevented tumor cell adhesion and invasion. These results provide direct evidence that although SW480 and SW620 cells do not express membrane-bound CD14, LPS in the presence of sCD14 can activate NF-kappaB, up-regulate beta(1) integrin expression, and subsequently promote tumor cell adhesion and invasion. Moreover, LPS-induced tumor cell attachment to and invasion through extracellular matrix proteins is beta(1) subunit-dependent.

Enhancement of the efficacy of x-irradiation by pentobarbital in a rodent brain-tumor model

International Nuclear Information System (INIS)

Olson, J.J.; Friedman, R.; Orr, K.; Delaney, T.; Oldfield, E.H.

1990-01-01

Radiation therapy is an important component of brain tumor treatment, but its efficacy is limited by its toxicity to the surrounding normal tissue. Pentobarbital acts as a cerebral radioprotectant, but the selectivity of its protection for the central nervous system has not been demonstrated. To determine if pentobarbital also protects tumor against ionizing radiation, five groups of Fischer 344 rats were observed after exposure to varying combinations of the presence or absence of implanted tumor, pentobarbital, and radiation treatment. The first three groups underwent cerebral implantations of a suspension of 9L gliosarcoma cells. Group 1 was left untreated and served as tumor-bearing controls. Group 2 received 30 Gy of whole-brain x-irradiation without anesthesia 8 days after tumor implantation. Group 3 received the same radiation treatment 15 minutes after pretreatment with 60 mg/kg of pentobarbital intraperitoneally. Groups 4 and 5 served as radiation controls, receiving 30 Gy of x-irradiation while awake and 30 Gy of x-irradiation after pentobarbital administration, respectively. Survival was calculated from the death of the last tumor-bearing rat. The mean survival time in tumor-bearing control rats was 20.8 +/- 2.6 days (+/- standard deviation). X-irradiation alone significantly enhanced the period of survival in rats implanted with the 9L tumor (29.7 +/- 5.6 days, p less than 0.03). Further significant prolongation of survival was seen with the addition of pentobarbital to the treatment regimen (39.9 +/- 13.5 days, p less than 0.01). Nontumor-bearing rats irradiated while awake (Group 4) survived 30.9 +/- 2.3 days. All of their pentobarbital-anesthetized counterparts in Group 5 survived. If pentobarbital had offered radioprotection to the tumor, then Group 3 would have had a shorter survival period than Group 2

Neural stem cell-encoded temporal patterning delineates an early window of malignant susceptibility in Drosophila.

Science.gov (United States)

Narbonne-Reveau, Karine; Lanet, Elodie; Dillard, Caroline; Foppolo, Sophie; Chen, Ching-Huan; Parrinello, Hugues; Rialle, Stéphanie; Sokol, Nicholas S; Maurange, Cédric

2016-06-14

Pediatric neural tumors are often initiated during early development and can undergo very rapid transformation. However, the molecular basis of this early malignant susceptibility remains unknown. During Drosophila development, neural stem cells (NSCs) divide asymmetrically and generate intermediate progenitors that rapidly differentiate in neurons. Upon gene inactivation, these progeny can dedifferentiate and generate malignant tumors. Here, we find that intermediate progenitors are prone to malignancy only when born during an early window of development while expressing the transcription factor Chinmo, and the mRNA-binding proteins Imp/IGF2BP and Lin-28. These genes compose an oncogenic module that is coopted upon dedifferentiation of early-born intermediate progenitors to drive unlimited tumor growth. In late larvae, temporal transcription factor progression in NSCs silences the module, thereby limiting mitotic potential and terminating the window of malignant susceptibility. Thus, this study identifies the gene regulatory network that confers malignant potential to neural tumors with early developmental origins.

Acute Metabolic Alkalosis Enhances Response of C3H Mouse Mammary Tumors to the Weak Base Mitoxantrone

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Natarajan Raghunand

2001-01-01

Full Text Available Uptake of weak acid and weak base chemotherapeutic drugs by tumors is greatly influenced by the tumor extracellular/interstitial pH (pHe, the intracellular pH (pHi maintained by the tumor cells, and by the ionization properties of the drug itself. The acid-outside plasmalemmal pH gradient in tumors acts to exclude weak base drugs like the anthracyclines, anthraquinones, and vinca alkaloids from the cells, leading to a substantial degree of “physiological drug resistance” in tumors. We have induced acute metabolic alkalosis in C3H tumor-bearing C3H/hen mice, by gavage and by intraperitoneal (i.p. administration of NaHCO3. 31P magnetic resonance spectroscopic measurements of 3-aminopropylphosphonate show increases of up to 0.6 pH units in tumor pHe, and 0.2 to 0.3 pH units in hind leg tissue pHe, within 2 hours of i.p. administration of NaHCO3. Theoretical calculations of mitoxantrone uptake into tumor and normal (hind leg tissue at the measured pH, and pHI values indicate that a gain in therapeutic index of up to 3.3-fold is possible with NaHCO3 pretreatment. Treatment of C3H tumor-bearing mice with 12 mg/kg mitoxantrone resulted in a tumor growth delay of 9 days, whereas combined NaHCO3mitoxantrone therapy resulted in an enhancement of the TGD to 16 days.

Can visual assessment of blood flow patterns by dynamic contrast-enhanced computed tomography distinguish between malignant and benign lung tumors?

DEFF Research Database (Denmark)

Harders, Stefan Walbom; Madsen, Hans Henrik; Nellemann, Hanne Marie

2017-01-01

with suspected lung cancer and a lung tumor on their chest radiograph were included for DCE-CT. The tumors were categorized using structured qualitative analysis of tumor blood flow patterns. Histopathology was used as reference standard. RESULTS: Using structured qualitative analysis of tumor blood flow...... using structured qualitative analysis of tumor blood flow patterns is accurate as well as somewhat reproducible. However, there are significant limitations to DCE-CT.......BACKGROUND: Dynamic contrast-enhanced computed tomography (DCE-CT) is a tool, which, in theory, can quantify the blood flow and blood volume of tissues. In structured qualitative analysis, parametric color maps yield a visual impression of the blood flow and blood volume within the tissue being...

Tumor cell culture on collagen–chitosan scaffolds as three-dimensional tumor model: A suitable model for tumor studies

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Aziz Mahmoudzadeh

2016-07-01

Full Text Available Tumor cells naturally live in three-dimensional (3D microenvironments, while common laboratory tests and evaluations are done in two-dimensional (2D plates. This study examined the impact of cultured 4T1 cancer cells in a 3D collagen–chitosan scaffold compared with 2D plate cultures. Collagen–chitosan scaffolds were provided and passed confirmatory tests. 4T1 tumor cells were cultured on scaffolds and then tumor cells growth rate, resistance to X-ray radiation, and cyclophosphamide as a chemotherapy drug were analyzed. Furthermore, 4T1 cells were extracted from the scaffold model and were injected into the mice. Tumor growth rate, survival rate, and systemic immune responses were evaluated. Our results showed that 4T1 cells infiltrated the scaffolds pores and constructed a 3D microenvironment. Furthermore, 3D cultured tumor cells showed a slower proliferation rate, increased levels of survival to the X-ray irradiation, and enhanced resistance to chemotherapy drugs in comparison with 2D plate cultures. Transfer of extracted cells to the mice caused enhanced tumor volume and decreased life span. This study indicated that collagen–chitosan nanoscaffolds provide a suitable model of tumor that would be appropriate for tumor studies.

Tumor cell culture on collagen-chitosan scaffolds as three-dimensional tumor model: A suitable model for tumor studies.

Science.gov (United States)

Mahmoudzadeh, Aziz; Mohammadpour, Hemn

2016-07-01

Tumor cells naturally live in three-dimensional (3D) microenvironments, while common laboratory tests and evaluations are done in two-dimensional (2D) plates. This study examined the impact of cultured 4T1 cancer cells in a 3D collagen-chitosan scaffold compared with 2D plate cultures. Collagen-chitosan scaffolds were provided and passed confirmatory tests. 4T1 tumor cells were cultured on scaffolds and then tumor cells growth rate, resistance to X-ray radiation, and cyclophosphamide as a chemotherapy drug were analyzed. Furthermore, 4T1 cells were extracted from the scaffold model and were injected into the mice. Tumor growth rate, survival rate, and systemic immune responses were evaluated. Our results showed that 4T1 cells infiltrated the scaffolds pores and constructed a 3D microenvironment. Furthermore, 3D cultured tumor cells showed a slower proliferation rate, increased levels of survival to the X-ray irradiation, and enhanced resistance to chemotherapy drugs in comparison with 2D plate cultures. Transfer of extracted cells to the mice caused enhanced tumor volume and decreased life span. This study indicated that collagen-chitosan nanoscaffolds provide a suitable model of tumor that would be appropriate for tumor studies. Copyright © 2016. Published by Elsevier B.V.

CpG Oligodeoxynucleotides Enhance the Efficacy of Adoptive Cell Transfer Using Tumor Infiltrating Lymphocytes by Modifying the Th1 Polarization and Local Infiltration of Th17 Cells

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Lin Xu

2010-01-01

Full Text Available Adoptive cell transfer immunotherapy using tumor infiltrating lymphocytes (TILs was an important therapeutic strategy against tumors. But the efficacy remains limited and development of new strategies is urgent. Recent evidence suggested that CpG-ODNs might be a potent candidate for tumor immunotherapy. Here we firstly reported that CpG-ODNs could significantly enhance the antitumor efficacy of adoptively transferred TILs in vivo accompanied by enhanced activity capacity and proliferation of CD8+ T cells and CD8+ T cells, as well as a Th1 polarization immune response. Most importantly, we found that CpG-ODNs could significantly elevate the infiltration of Th17 cells in tumor mass, which contributed to anti-tumor efficacy of TILs in vivo. Our findings suggested that CpG ODNs could enhance the anti-tumor efficacy of adoptively transferred TILs through modifying Th1 polarization and local infiltration of Th17 cells, which might provide a clue for developing a new strategy for ACT based on TILs.

MRI for characterization of primary tumors in the non-cirrhotic liver: Added value of Gd-EOB-DTPA enhanced hepatospecific phase

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Donati, Olivio F.; Hunziker, Roger; Fischer, Michael A. [Institute of Diagnostic and Interventional Radiology, University Hospital Zurich, Zurich (Switzerland); Raptis, Dimitri A.; Breitenstein, Stefan [Department of Visceral and Transplant Surgery, Swiss Hepato-Pancreato-Biliary (HPB) Center, University Hospital Zurich, Zurich (Switzerland); Patak, Michael A., E-mail: Michael.Patak@hirslanden.ch [Institute of Diagnostic and Interventional Radiology, University Hospital Zurich, Zurich (Switzerland); Clinic Hirslanden, Hirslanden Hospital Group, Zurich (Switzerland)

2014-07-15

Purpose: To evaluate the added value of hepatospecific phase in Gd-EOB-DTPA enhanced magnetic resonance imaging (MRI) in patients with primary tumors in non-cirrhotic liver. Methods: Twenty-nine patients (median, 39 years; range, 18–81 years; 11 male) underwent preoperative Gd-EOB-DTPA enhanced MRI including hepatospecific phase after 10 and 20 min of contrast injection at four institutions in Europe, North America and New Zealand. Images were evaluated by three different readers (R1–R3) who characterized liver tumors with and without consultation of the hepatospecific phase images. Confidence in diagnosis was scored on a visual analog scale from 1 to 10. Histopathology (adenoma, n = 5; focal nodular hyperplasia, n = 11 and hepatocellular carcinoma, n = 13) in all patients served as the standard of reference. Differences were evaluated using the McNemar and Wilcoxon signed rank test. Results: Without hepatospecific phase images available, 22 (76%), 19 (66%) and 19 (66%) of 29 tumors were characterized correctly by the three readers respectively. Mean confidence in diagnosis was 6.1, 5.7 and 5.8. With the hepatospecific phase included, characterization of liver tumors did not change significantly with 21 (72%), 23 (79%) and 19 (66%) of 29 tumors diagnosed correctly (p > 0.05). According confidence ratings increased to 6.3, 6.5 and 7.7, respectively. Increase in diagnostic confidence was significant for R2 and R3 (p < 0.05) and independent of reader's experience. Conclusion: The additional hepatospecific phase in Gd-EOB-DTPA enhanced MRI did not significantly increase diagnostic accuracy in characterization of primary tumors in the non-cirrhotic liver. However, 2/3 readers showed a significant increase in diagnostic confidence after consultation of the hepatospecific phase.

Enhanced cocaine-induced locomotor sensitization and intrinsic excitability of NAc medium spiny neurons in adult but not adolescent rats susceptible to diet-induced obesity

Science.gov (United States)

Oginsky, Max F.; Maust, Joel D.; Corthell, John T.; Ferrario, Carrie R.

2015-01-01

Rationale Basal and diet-induced differences in mesolimbic function, particularly within the nucleus accumbens (NAc), may contribute to human obesity; these differences may be more pronounced in susceptible populations. Objectives We determined whether there are differences in cocaine-induced behavioral plasticity in rats that are susceptible vs. resistant to diet-induced obesity, and basal differences in the striatal neuron function in adult and adolescent obesity-prone and obesity-resistant rats. Methods Susceptible and resistant outbred rats were identified based on “junk-food” diet-induced obesity. Then, the induction and expression of cocaine-induced locomotor sensitization, which is mediated by enhanced striatal function and is associated with increased motivation for rewards and reward-paired cues, were evaluated. Basal differences in mesolimbic function were examined in selectively bred obesity-prone and obesity-resistant rats (P70-80 and P30-40) using both cocaine induced locomotion and whole-cell patch clamping approaches in NAc core medium spiny neurons (MSNs). Results In rats that became obese after eating “junk-food”, the expression of locomotor sensitization was enhanced compared to non-obese rats, with similarly strong responses to 7.5 and 15 mg/kg cocaine. Without diet manipulation, obesity-prone rats were hyper-responsive to the acute locomotor-activating effects of cocaine, and the intrinsic excitability of NAc core MSNs was enhanced by ~60% at positive and negative potentials. These differences were present in adult, but not adolescent rats. Post-synaptic glutamatergic transmission was similar between groups. Conclusions Mesolimbic systems, particularly NAc MSNs, are hyper-responsive in obesity-prone individuals; and interactions between predisposition and experience influence neurobehavioral plasticity in ways that may promote weight gain and hamper weight loss in susceptible rats. PMID:26612617

Dynamic contrast enhanced MRI study of primary primitive neuroectodermal tumor in the thoracic spine

International Nuclear Information System (INIS)

Chen Yu; Xu Jianmin; Li Ying; Zhang Jingzhong; Zhu Jing

2004-01-01

Objective: To investigate the value of dynamic contrast-enhanced MR imaging in the diagnosis and differentiation of primitive neuroectodermal tumor (PNET) in the thoracic spine. Methods: The dynamic contrast-enhanced MR imaging of 2 patients (3 times) with PNET in the thoracic spine proved by surgery and pathology were prospectively studied. Results: In the curves of SI-time and CER-time, PNET in the thoracic spine showed a rapid rise to the peak between 60 s and 120 s, then the flat level was kept and no obvious decline was detected after about 3.5 minute. Conclusion: Dynamic contrast-enhanced MRI can help to make the diagnosis and differential diagnosis for PNET in the thoracic spine, offer reliable information for the choice of clinical management, and predict the prognosis

Computed tomography of liver tumors, 2. Differential diagnosis between hepatocellular carcinoma and metastatic hepatic tumor by dynamic CT scanning

Energy Technology Data Exchange (ETDEWEB)

Naito, Akira; Fukuoka, Haruhito; Kashiwado, Kouzou; Ichiki, Toshio; Makidono, Yoko [Hiroshima Red Cross Hospital (Japan)

1984-02-01

Differential diagnosis between hepatocellular carcinoma and metastatic hepatic tumor was attempted using dynamic CT scanning. Homogeneous and patchy types were peculiar to hepatocellular carcinoma, and ring-like type to metastatic hepatic tumor. However, with no enhancement, hepatocellular carcinoma could not be denied. Hepatocellular carcinoma was characterized by the enhancement shown on the early stage of dynamic CT. Ring enhancement was not visualized on dynamic CT but visualized on conventional contrast enhanced CT in hepatocellular carcinomas; it was visualized on conventional contrast enhanced CT and on dynamic CT in metastatic hepatic tumors.

Increased apoptotic potential and dose-enhancing effect of gold nanoparticles in combination with single-dose clinical electron beams on tumor-bearing mice

International Nuclear Information System (INIS)

Chang Mengya; Chen Yuhung; Chang Chihjui; Chen Helen H-W; Wu Chaoliang; Shiau Aili

2008-01-01

High atomic number material, such as gold, may be used in conjunction with radiation to provide dose enhancement in tumors. In the current study, we investigated the dose-enhancing effect and apoptotic potential of gold nanoparticles in combination with single-dose clinical electron beams on B16F10 melanoma tumor-bearing mice. We revealed that the accumulation of gold nanoparticles was detected inside B16F10 culture cells after 18 h of incubation, and moreover, the gold nanoparticles were shown to be colocalized with endoplasmic reticulum and Golgi apparatus in cells. Furthermore, gold nanoparticles radiosensitized melanoma cells in the colony formation assay (P=0.02). Using a B16F10 tumor-bearing mouse model, we further demonstrated that gold nanoparticles in conjunction with ionizing radiation significantly retarded tumor growth and prolonged survival compared to the radiation alone controls (P<0.05). Importantly, an increase of apoptotic signals was detected inside tumors in the combined treatment group (P<0.05). Knowing that radiation-induced apoptosis has been considered a determinant of tumor responses to radiation therapy, and the length of tumor regrowth delay correlated with the extent of apoptosis after single-dose radiotherapy, these results may suggest the clinical potential of gold nanoparticles in improving the outcome of melanoma radiotherapy. (author)

The association between miR-499 polymorphism and cancer susceptibility: a meta-analysis

Directory of Open Access Journals (Sweden)

Xu Z

2015-08-01

Full Text Available Zhongfei Xu, Enjiao Zhang, Weiyi Duan, Changfu Sun, Shuang Bai, Xuexin Tan Department of Oral and Maxillofacial Surgery, School of Stomatology, China Medical University, Shenyang, People’s Republic of China Background: MicroRNAs are a class of new noncoding RNA that play important roles in the pathogenesis of tumor. Rs3746444 in miR-499 is suggested to be associated with cancer susceptibility. In the present study, we assess the association between miR-499 rs3746444 polymorphism and cancer susceptibility through a meta-analysis. Methods: We searched relevant articles from the PubMed and Embase databases. We screened all the resulting articles for adherence to the inclusion and exclusion criteria. The associations between miR-499 polymorphism and cancer susceptibility were estimated by computing the odds ratios (ORs and 95% confidence intervals (CIs. All analyses were performed using Stata software. Results: There are 18 datasets included in the analysis. Statistically significant associations were found between the miR-499 rs3746444 polymorphism and susceptibility to cancer (GG versus AA: OR =1.24, 95% CI: 1.01–1.52; G versus A: OR =1.11, 95% CI: 1.01–1.23. A subsequent analysis, on the basis of ethnicity for the population characteristic, showed that Asians had increased susceptibility to cancer (GG versus AA: OR =1.32, 95% CI: 1.09–1.59; GG + AG versus AA: OR = 1.17, 95% CI: 1.01–1.37. In the subgroup analysis of tumor type, none of the genetic models had statistically significant results. The meta-regression suggested that race and cancer types are not the source of heterogeneity in the present meta-analysis. No publication bias was detected by either the inverted funnel plot or Egger’s test. Conclusion: Rs3746444 in miR-499 might be related to susceptibility to cancer. Keywords: microRNA, single-nucleotide polymorphism, tumor, risk factor

Surface-enhanced Raman spectroscopy of saliva proteins for the noninvasive differentiation of benign and malignant breast tumors

Science.gov (United States)

Feng, Shangyuan; Huang, Shaohua; Lin, Duo; Chen, Guannan; Xu, Yuanji; Li, Yongzeng; Huang, Zufang; Pan, Jianji; Chen, Rong; Zeng, Haishan

2015-01-01

The capability of saliva protein analysis, based on membrane protein purification and surface-enhanced Raman spectroscopy (SERS), for detecting benign and malignant breast tumors is presented in this paper. A total of 97 SERS spectra from purified saliva proteins were acquired from samples obtained from three groups: 33 healthy subjects; 33 patients with benign breast tumors; and 31 patients with malignant breast tumors. Subtle but discernible changes in the mean SERS spectra of the three groups were observed. Tentative assignments of the saliva protein SERS spectra demonstrated that benign and malignant breast tumors led to several specific biomolecular changes of the saliva proteins. Multiclass partial least squares–discriminant analysis was utilized to analyze and classify the saliva protein SERS spectra from healthy subjects, benign breast tumor patients, and malignant breast tumor patients, yielding diagnostic sensitivities of 75.75%, 72.73%, and 74.19%, as well as specificities of 93.75%, 81.25%, and 86.36%, respectively. The results from this exploratory work demonstrate that saliva protein SERS analysis combined with partial least squares–discriminant analysis diagnostic algorithms has great potential for the noninvasive and label-free detection of breast cancer. PMID:25609959

Blockade of the ERK pathway enhances the therapeutic efficacy of the histone deacetylase inhibitor MS-275 in human tumor xenograft models

Energy Technology Data Exchange (ETDEWEB)

Sakamoto, Toshiaki; Ozaki, Kei-ichi; Fujio, Kohsuke; Kajikawa, Shu-hei [Laboratory of Cell Regulation, Department of Pharmaceutical Sciences, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8521 (Japan); Uesato, Shin-ichi [Department of Biotechnology, Faculty of Engineering, Kansai University, Osaka 564-8680 (Japan); Watanabe, Kazushi [Proubase Technology Inc., Kanagawa 211-0063 (Japan); Tanimura, Susumu [Laboratory of Cell Regulation, Department of Pharmaceutical Sciences, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8521 (Japan); Koji, Takehiko [Department of Histology and Cell Biology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523 (Japan); Kohno, Michiaki, E-mail: kohnom@nagasaki-u.ac.jp [Laboratory of Cell Regulation, Department of Pharmaceutical Sciences, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8521 (Japan); Proubase Technology Inc., Kanagawa 211-0063 (Japan); Kyoto University Graduate School of Pharmaceutical Sciences, Kyoto 606-8501 (Japan)

2013-04-19

Highlights: •Blockade of the ERK pathway enhances the anticancer efficacy of HDAC inhibitors. •MEK inhibitors sensitize human tumor xenografts to HDAC inhibitor cytotoxicity. •Such the enhanced efficacy is achieved by a transient blockade of the ERK pathway. •This drug combination provides a promising therapeutic strategy for cancer patients. -- Abstract: The ERK pathway is up-regulated in various human cancers and represents a prime target for mechanism-based approaches to cancer treatment. Specific blockade of the ERK pathway alone induces mostly cytostatic rather than pro-apoptotic effects, however, resulting in a limited therapeutic efficacy of the ERK kinase (MEK) inhibitors. We previously showed that MEK inhibitors markedly enhance the ability of histone deacetylase (HDAC) inhibitors to induce apoptosis in tumor cells with constitutive ERK pathway activation in vitro. To evaluate the therapeutic efficacy of such drug combinations, we administered the MEK inhibitor PD184352 or AZD6244 together with the HDAC inhibitor MS-275 in nude mice harboring HT-29 or H1650 xenografts. Co-administration of the MEK inhibitor markedly sensitized the human xenografts to MS-275 cytotoxicity. A dose of MS-275 that alone showed only moderate cytotoxicity thus suppressed the growth of tumor xenografts almost completely as well as induced a marked reduction in tumor cellularity when administered with PD184352 or AZD6244. The combination of the two types of inhibitor also induced marked oxidative stress, which appeared to result in DNA damage and massive cell death, specifically in the tumor xenografts. The enhanced therapeutic efficacy of the drug combination was achieved by a relatively transient blockade of the ERK pathway. Administration of both MEK and HDAC inhibitors represents a promising chemotherapeutic strategy with improved safety for cancer patients.

Bromodomain protein 4 discriminates tissue-specific super-enhancers containing disease-specific susceptibility loci in prostate and breast cancer

DEFF Research Database (Denmark)

Zuber, Verena; Bettella, Francesco; Witoelar, Aree

2017-01-01

progression. Although previous approaches have been tried to explain risk associated with SNPs in regulatory DNA elements, so far epigenetic readers such as bromodomain containing protein 4 (BRD4) and super-enhancers have not been used to annotate SNPs. In prostate cancer (PC), androgen receptor (AR) binding......Background: Epigenetic information can be used to identify clinically relevant genomic variants single nucleotide polymorphisms (SNPs) of functional importance in cancer development. Super-enhancers are cell-specific DNA elements, acting to determine tissue or cell identity and driving tumor...... the differential enrichment of SNPs mapping to specific categories of enhancers. We find that BRD4 is the key discriminant of tissue-specific enhancers, showing that it is more powerful than AR binding information to capture PC specific risk loci, and can be used with similar effect in breast cancer (BC...

Chemotherapy-Induced IL34 Enhances Immunosuppression by Tumor-Associated Macrophages and Mediates Survival of Chemoresistant Lung Cancer Cells

OpenAIRE

Baghdadi, Muhammad; Wada, Haruka; Nakanishi, Sayaka; Abe, Hirotake; Han, Nanumi; Putra, Wira Eka; Endo, Daisuke; Watari, Hidemichi; Sakuragi, Noriaki; Hida, Yasuhiro; Kaga, Kichizo; Miyagi, Yohei; Yokose, Tomoyuki; Takano, Atsushi; Daigo, Yataro

2016-01-01

The ability of tumor cells to escape immune destruction and their acquired resistance to chemotherapy are major obstacles to effective cancer therapy. Although immune checkpoint therapies such as anti-PD-1 address these issues in part, clinical responses remain limited to a subpopulation of patients. In this report, we identified IL34 produced by cancer cells as a driver of chemoresistance. In particular, we found that IL34 modulated the functions of tumor-associated macrophages to enhance lo...

Computed tomographic diagnosis of parotid gland tumor

International Nuclear Information System (INIS)

Matsunaga, Hitoki; Nishimura, Tadao; Takasu, Akihiko; Yagizawa, Mikio; Suzuki, Akio

1983-01-01

Investigation with CT has been performed on 20 cases of parotid gland tumors. The intravenous contrast enhancement method was performed in all cases. Six cases were examined by CT and simultaneous sialography. The results were as follows: 1) If and when the margin of the tumor was indistinct and irregular, malignancy was suspected. However, it was difficult to diagnose malignancy by CT examination only. 2) CT for parotid gland tumor was effective in indentifying invasion of tumor into the parapharyngeal space and intracranial space. 3) CT with simultaneous sialography was very effective in locating the parotid gland tumor. 4) CT of axial sections for parotid gland tumor was more reliable if coronaly sections are taken together. 5) CT of malignant and benign tumors were diffusely enhanced by the intravenous contrast enhancement method. However, this was not an indispensable method. (author)

Enhancing tumor apparent diffusion coefficient histogram skewness stratifies the postoperative survival in recurrent glioblastoma multiforme patients undergoing salvage surgery.

Science.gov (United States)

Zolal, Amir; Juratli, Tareq A; Linn, Jennifer; Podlesek, Dino; Sitoci Ficici, Kerim Hakan; Kitzler, Hagen H; Schackert, Gabriele; Sobottka, Stephan B; Rieger, Bernhard; Krex, Dietmar

2016-05-01

Objective To determine the value of apparent diffusion coefficient (ADC) histogram parameters for the prediction of individual survival in patients undergoing surgery for recurrent glioblastoma (GBM) in a retrospective cohort study. Methods Thirty-one patients who underwent surgery for first recurrence of a known GBM between 2008 and 2012 were included. The following parameters were collected: age, sex, enhancing tumor size, mean ADC, median ADC, ADC skewness, ADC kurtosis and fifth percentile of the ADC histogram, initial progression free survival (PFS), extent of second resection and further adjuvant treatment. The association of these parameters with survival and PFS after second surgery was analyzed using log-rank test and Cox regression. Results Using log-rank test, ADC histogram skewness of the enhancing tumor was significantly associated with both survival (p = 0.001) and PFS after second surgery (p = 0.005). Further parameters associated with prolonged survival after second surgery were: gross total resection at second surgery (p = 0.026), tumor size (0.040) and third surgery (p = 0.003). In the multivariate Cox analysis, ADC histogram skewness was shown to be an independent prognostic factor for survival after second surgery. Conclusion ADC histogram skewness of the enhancing lesion, enhancing lesion size, third surgery, as well as gross total resection have been shown to be associated with survival following the second surgery. ADC histogram skewness was an independent prognostic factor for survival in the multivariate analysis.

Extracellular pH Modulates Neuroendocrine Prostate Cancer Cell Metabolism and Susceptibility to the Mitochondrial Inhibitor Niclosamide

Science.gov (United States)

Ippolito, Joseph E.; Brandenburg, Matthew W.; Ge, Xia; Crowley, Jan R.; Kirmess, Kristopher M.; Som, Avik; D’Avignon, D. Andre; Arbeit, Jeffrey M.; Achilefu, Samuel; Yarasheski, Kevin E.; Milbrandt, Jeffrey

2016-01-01

Neuroendocrine prostate cancer is a lethal variant of prostate cancer that is associated with castrate-resistant growth, metastasis, and mortality. The tumor environment of neuroendocrine prostate cancer is heterogeneous and characterized by hypoxia, necrosis, and numerous mitoses. Although acidic extracellular pH has been implicated in aggressive cancer features including metastasis and therapeutic resistance, its role in neuroendocrine prostate cancer physiology and metabolism has not yet been explored. We used the well-characterized PNEC cell line as a model to establish the effects of extracellular pH (pH 6.5, 7.4, and 8.5) on neuroendocrine prostate cancer cell metabolism. We discovered that alkalinization of extracellular pH converted cellular metabolism to a nutrient consumption-dependent state that was susceptible to glucose deprivation, glutamine deprivation, and 2-deoxyglucose (2-DG) mediated inhibition of glycolysis. Conversely, acidic pH shifted cellular metabolism toward an oxidative phosphorylation (OXPHOS)-dependent state that was susceptible to OXPHOS inhibition. Based upon this mechanistic knowledge of pH-dependent metabolism, we identified that the FDA-approved anti-helminthic niclosamide depolarized mitochondrial potential and depleted ATP levels in PNEC cells whose effects were enhanced in acidic pH. To further establish relevance of these findings, we tested the effects of extracellular pH on susceptibility to nutrient deprivation and OXPHOS inhibition in a cohort of castrate-resistant prostate cancer cell lines C4-2B, PC-3, and PC-3M. We discovered similar pH-dependent toxicity profiles among all cell lines with these treatments. These findings underscore a potential importance to acidic extracellular pH in the modulation of cell metabolism in tumors and development of an emerging paradigm that exploits the synergy of environment and therapeutic efficacy in cancer. PMID:27438712

Hemodynamic analysis of bladder tumors using T1-dynamic contrast-enhanced fast spin-echo MRI

International Nuclear Information System (INIS)

Kanazawa, Yuki; Miyati, Tosiaki; Sato, Osamu

2012-01-01

Objectives: To evaluate the hemodynamics of bladder tumors, we developed a method to calculate change in R 1 value (ΔR 1 ) from T 1 -dynamic contrast-enhanced fast spin-echo magnetic resonance imaging (T 1 DCE-FSE-MRI). Materials and methods: On a 1.5-T MR system, T 1 DCE-FSE-MRI was performed. This study was applied to 12 patients with urinary bladder tumor, i.e. urothelial carcinoma. We compared ΔR 1 –time and ΔSI–time between a peak in the ΔR 1 –time and ΔSI–time curve occurred during the first pass within 60 s. Next, we assessed the slope of increase for 180 s after CA injection (Slope 0–180 ). Results: The mean slope of the first pass was significantly higher for bladder tumors on both the ΔR 1 –time and the ΔSI–time curve compared with normal bladder walls. Moreover, a significant difference was apparent between bladder tumors and normal bladder walls on the mean Slope 0–180 in the ΔR 1 -time curve. However, no significant difference in the mean Slope 0–180 was observed on the ΔSI-time curve between bladder tumors and normal bladder walls. Conclusion: T 1 DCE-FSE-MRI offers three advantages: quantitative analysis; high-quality (i.e., artifact-free) images; and high temporal resolution even for SE images. Use of ΔR 1 analysis with T 1 DCE-FSE-MRI allows more detailed information on the hemodynamics of bladder tumors to be obtained and assists in differentiation between bladder tumors and the normal bladder wall.

Synergistic enhancement of iron oxide nanoparticle and gadolinium for dual-contrast MRI

International Nuclear Information System (INIS)

Zhang, Fan; Huang, Xinglu; Qian, Chunqi; Zhu, Lei; Hida, Naoki; Niu, Gang; Chen, Xiaoyuan

2012-01-01

Highlights: ► MR contrast agents exert influence on T 1 or T 2 relaxation time of the surrounding tissue. ► Combined use of iron oxide and Gd-DTPA can improve the sensitivity/specificity of lesion detection. ► Dual contrast MRI enhances the delineation of tumor borders and small lesions. ► The effect of DC-MRI can come from the high paramagnetic susceptibility of Gd 3+ . ► The effect of DC-MRI can also come from the distinct pharmacokinetic distribution of SPIO and Gd-DTPA. -- Abstract: Purpose: The use of MR contrast agents allows accurate diagnosis by exerting an influence on the longitudinal (T 1 ) or transverse (T 2 ) relaxation time of the surrounding tissue. In this study, we combined the use of iron oxide (IO) particles and nonspecific extracellular gadolinium chelate (Gd) in order to further improve the sensitivity and specificity of lesion detection. Procedures: With a 7-Tesla scanner, pre-contrasted, IO-enhanced and dual contrast agent enhanced MRIs were performed in phantom, normal animals, and animal models of lymph node tumor metastases and orthotopic brain tumor. For the dual-contrast (DC) MRI, we focused on the evaluation of T 2 weighted DC MRI with IO administered first, then followed by the injection of a bolus of gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA). Results: Based on the C/N ratios and MRI relaxometry, the synergistic effect of coordinated administration of Gd-DTPA and IO was observed and confirmed in phantom, normal liver and tumor models. At 30 min after administration of Feridex, Gd-DTPA further decreased T 2 relaxation in liver immediately after the injection. Additional administration of Gd-DTPA also immediately increased the signal contrast between tumor and brain parenchyma and maximized the C/N ratio to −4.12 ± 0.71. Dual contrast MRI also enhanced the delineation of tumor borders and small lesions. Conclusions: DC-MRI will be helpful to improve diagnostic accuracy and decrease the threshold size for

Tumor vessel normalization after aerobic exercise enhances chemotherapeutic efficacy.

Science.gov (United States)

Schadler, Keri L; Thomas, Nicholas J; Galie, Peter A; Bhang, Dong Ha; Roby, Kerry C; Addai, Prince; Till, Jacob E; Sturgeon, Kathleen; Zaslavsky, Alexander; Chen, Christopher S; Ryeom, Sandra

2016-10-04

Targeted therapies aimed at tumor vasculature are utilized in combination with chemotherapy to improve drug delivery and efficacy after tumor vascular normalization. Tumor vessels are highly disorganized with disrupted blood flow impeding drug delivery to cancer cells. Although pharmacologic anti-angiogenic therapy can remodel and normalize tumor vessels, there is a limited window of efficacy and these drugs are associated with severe side effects necessitating alternatives for vascular normalization. Recently, moderate aerobic exercise has been shown to induce vascular normalization in mouse models. Here, we provide a mechanistic explanation for the tumor vascular normalization induced by exercise. Shear stress, the mechanical stimuli exerted on endothelial cells by blood flow, modulates vascular integrity. Increasing vascular shear stress through aerobic exercise can alter and remodel blood vessels in normal tissues. Our data in mouse models indicate that activation of calcineurin-NFAT-TSP1 signaling in endothelial cells plays a critical role in exercise-induced shear stress mediated tumor vessel remodeling. We show that moderate aerobic exercise with chemotherapy caused a significantly greater decrease in tumor growth than chemotherapy alone through improved chemotherapy delivery after tumor vascular normalization. Our work suggests that the vascular normalizing effects of aerobic exercise can be an effective chemotherapy adjuvant.

Monte Carlo modeling and optimization of contrast-enhanced radiotherapy of brain tumors

Energy Technology Data Exchange (ETDEWEB)

Perez-Lopez, C E; Garnica-Garza, H M, E-mail: hgarnica@cinvestav.mx [Centro de Investigacion y de Estudios Avanzados del Instituto Politecnico Nacional Unidad Monterrey, Via del Conocimiento 201 Parque de Investigacion e Innovacion Tecnologica, Apodaca NL CP 66600 (Mexico)

2011-07-07

Contrast-enhanced radiotherapy involves the use of a kilovoltage x-ray beam to impart a tumoricidal dose to a target into which a radiological contrast agent has previously been loaded in order to increase the x-ray absorption efficiency. In this treatment modality the selection of the proper x-ray spectrum is important since at the energy range of interest the penetration ability of the x-ray beam is limited. For the treatment of brain tumors, the situation is further complicated by the presence of the skull, which also absorbs kilovoltage x-ray in a very efficient manner. In this work, using Monte Carlo simulation, a realistic patient model and the Cimmino algorithm, several irradiation techniques and x-ray spectra are evaluated for two possible clinical scenarios with respect to the location of the target, these being a tumor located at the center of the head and at a position close to the surface of the head. It will be shown that x-ray spectra, such as those produced by a conventional x-ray generator, are capable of producing absorbed dose distributions with excellent uniformity in the target as well as dose differential of at least 20% of the prescribed tumor dose between this and the surrounding brain tissue, when the tumor is located at the center of the head. However, for tumors with a lateral displacement from the center and close to the skull, while the absorbed dose distribution in the target is also quite uniform and the dose to the surrounding brain tissue is within an acceptable range, hot spots in the skull arise which are above what is considered a safe limit. A comparison with previously reported results using mono-energetic x-ray beams such as those produced by a radiation synchrotron is also presented and it is shown that the absorbed dose distributions rendered by this type of beam are very similar to those obtained with a conventional x-ray beam.

Enhancing predicted efficacy of tumor treating fields therapy of glioblastoma using targeted surgical craniectomy: A computer modeling study

DEFF Research Database (Denmark)

Korshoej, Anders Rosendal; Saturnino, Guilherme Bicalho; Rasmussen, Line Kirkegaard

2016-01-01

the potential of the intervention to improve the clinical efficacy of TTFields therapy of brain cancer. Methods: We used finite element analysis to calculate the electrical field distribution in realistic head models based on MRI data from two patients: One with left cortical/subcortical glioblastoma and one......Objective: The present work proposes a new clinical approach to TTFields therapy of glioblastoma. The approach combines targeted surgical skull removal (craniectomy) with TTFields therapy to enhance the induced electrical field in the underlying tumor tissue. Using computer simulations, we explore...... with deeply seated right thalamic anaplastic astrocytoma. Field strength was assessed in the tumor regions before and after virtual removal of bone areas of varying shape and size (10 to 100 mm) immediately above the tumor. Field strength was evaluated before and after tumor resection to assess realistic...

uPAR-controlled oncolytic adenoviruses eliminate cancer stem cells in human pancreatic tumors.

Science.gov (United States)

Sobrevals, Luciano; Mato-Berciano, Ana; Urtasun, Nerea; Mazo, Adela; Fillat, Cristina

2014-01-01

Pancreatic tumors contain cancer stem cells highly resistant to chemotherapy. The identification of therapies that can eliminate this population of cells might provide with more effective treatments. In the current work we evaluated the potential of oncolytic adenoviruses to act against pancreatic cancer stem cells (PCSC). PCSC from two patient-derived xenograft models were isolated from orthotopic pancreatic tumors treated with saline, or with the chemotherapeutic agent gemcitabine. An enrichment in the number of PCSC expressing the cell surface marker CD133 and a marked enhancement on tumorsphere formation was observed in gemcitabine treated tumors. No significant increase in the CD44, CD24, and epithelial-specific antigen (ESA) positive cells was observed. Neoplastic sphere-forming cells were susceptible to adenoviral infection and exposure to oncolytic adenoviruses resulted in elevated cytotoxicity with both Adwt and the tumor specific AduPARE1A adenovirus. In vivo, intravenous administration of a single dose of AduPARE1A in human-derived pancreatic xenografts led to a remarkable anti-tumor effect. In contrast to gemcitabine AduPARE1A treatment did not result in PCSC enrichment. No enrichment on tumorspheres neither on the CD133(+) population was detected. Therefore our data provide evidences of the relevance of uPAR-controlled oncolytic adenoviruses for the elimination of pancreatic cancer stem cells. © 2013.

Susceptibility weighted imaging (SWI) of the kidney at 3 T. Initial results

International Nuclear Information System (INIS)

Mie, Moritz B.; Zoellner, Frank G.; Heilmann, Melanie; Schad, Lothar R.; Nissen, Johanna C.; Schoenberg, Stefan O.; Michaely, Henrik J.

2010-01-01

Susceptibility weighted imaging provides diagnostic information in strokes, hemorrhages, and cerebral tumors and has proven to be a valuable tool in imaging venous vessels in the cerebrum. The SWI principle is based on the weighting of T 2 * weighted magnitude images with a phase mask, therewith improving image contrast of veins or neighbouring structures of different susceptibility, in general. T 2 * weighted MRI is already used for assessment of kidney function. In this paper, the feasibility of SWI on kidneys was investigated. Translation of SWI from the brain to the kidneys comes along with two main challenges: (i) organ motion due to breathing and (ii) a higher oxygenation level of renal veins compared to the brain. To handle these problems, the acquisition time has been cut down to allow for breath-hold examinations, and different post-processing methods including a new phase mask were investigated to visualize renal veins. Results showed that by a new post-processing strategy SWI contrast was enhanced on average by a factor of 1.33 compared to the standard phase mask. In summary, initial experiences of SWI on the kidneys demonstrated the feasibility. However, further technical developments have to be performed to make this technology applicable in clinical abdominal MRI. (orig.)

Poly(γ-glutamic acid)-coated lipoplexes loaded with Doxorubicin for enhancing the antitumor activity against liver tumors

Science.gov (United States)

Qi, Na; Tang, Bo; Liu, Guang; Liang, Xingsi

2017-05-01

The study was to develop poly-γ-glutamic acid (γ-PGA)-coated Doxorubicin (Dox) lipoplexes that enhance the antitumor activity against liver tumors. γ-PGA-coated lipoplexes were performed by electrostatistically attracting to the surface of cationic charge liposomes with anionic γ-PGA. With the increasing of γ-PGA concentration, the particle size of γ-PGA-coated Dox lipoplexes slightly increased, the zeta potential from positive shifted to negative, and the entrapment efficiency (EE) were no significant change. The release rate of γ-PGA-coated Dox lipoplexes slightly increased at acidic pH, the accelerated Dox release might be attributed to greater drug delivery to tumor cells, resulting in a higher antitumor activity. Especially, γ-PGA-coated Dox lipoplexes exhibited higher cellular uptake, significant in vitro cytotoxicity in HepG2 cells, and improved in vivo antitumor efficacy toward HepG2 hepatoma-xenografted nude models in comparison with Dox liposomes and free Dox solution. In addition, the analysis results via flow cytometry showed that γ-PGA-coated Dox lipoplexes induce S phase cell cycle arrest and significantly increased apoptosis rate of HepG2 cells. In conclusion, the presence of γ-PGA on the surface of Dox lipoplexes enhanced antitumor effects of liver tumors.

Intratumoral delivery of CpG-conjugated anti-MUC1 antibody enhances NK cell anti-tumor activity.

Science.gov (United States)

Schettini, Jorge; Kidiyoor, Amritha; Besmer, Dahlia M; Tinder, Teresa L; Roy, Lopamudra Das; Lustgarten, Joseph; Gendler, Sandra J; Mukherjee, Pinku

2012-11-01

Monoclonal antibodies (mAbs) against tumor-associated antigens are useful anticancer agents. Antibody-dependent cellular cytotoxicity (ADCC) is one of the major mechanisms responsible for initiating natural killer cell (NK)-mediated killing of tumors. However, the regulation of ADCC via NK cells is poorly understood. We have investigated the cytolytic activity of NK cells against pancreatic cancer cells that were coated with an antibody directed against the human tumor antigen, Mucin-1 designated HMFG-2, either alone or conjugated to CpG oligodeoxynucleotide (CpG ODN). Conjugated antibodies were tested for their ability to elicit ADCC in vitro and in vivo against pancreatic cancer cells. NK cells cultured in the presence of immobilized CpG ODN, HMFG-2 Ab, or CpG ODN-conjugated HMFG-2 Ab were able to up-regulate perforin similarly. Interestingly, a significant higher ADCC was observed when CpG ODN-conjugated HMFG-2-coated tumor cells were co-cultured with NK cells compared to unconjugated HMFG-2 Ab or CpG ODN alone. Moreover, MyD88-deficient NK cells can perform ADCC in vitro. Furthermore, intratumoral injections of CpG ODN-conjugated HMFG-2 induced a significant reduction in tumor burden in vivo in an established model of pancreatic tumor in nude mice compared to CpG ODN or the HMFG-2 alone. Depletion of macrophages or NK cells before treatment confirmed that both cells were required for the anti-tumor response in vivo. Results also suggest that CpG ODN and HMFG-2 Ab could be sensed by NK cells on the mAb-coated tumor cells triggering enhanced ADCC in vitro and in vivo.

Children's differential susceptibility to parenting : An experimental test of “for better and for worse”

NARCIS (Netherlands)

Slagt, Meike; Dubas, Judith Semon; van Aken, Marcel; Ellis, Bruce J.; Dekovic, Maja

2017-01-01

Differential susceptibility theory proposes that a subset of individuals exist who display enhanced susceptibility to both negative (risk-promoting) and positive (development-enhancing) environments. This experiment represents the first attempt to directly test this assumption by exposing children

Contrast-Enhanced Ultrasonography of Hepatocellular Carcinoma After Chemoembolisation Using Drug-Eluting Beads: A Pilot Study Focused on Sustained Tumor Necrosis

International Nuclear Information System (INIS)

Moschouris, Hippocrates; Malagari, Katerina; Papadaki, Marina Georgiou; Kornezos, Ioannis; Matsaidonis, Dimitrios

2010-01-01

The purpose of this study was to assess the use of contrast-enhanced ultrasonography (CEUS) and the sustained antitumor effect of drug-eluting beads used for transarterial chemoembolisation (TACE) of unresectable hepatocellular carcinoma (HCC). Ten patients with solitary, unresectable HCC underwent CEUS before, 2 days after, and 35 to 40 days after TACE using a standard dose (4 ml) of drug-eluting beads (DC Beads; Biocompatibles, Surrey, UK) preloaded with doxorubicin (25 mg doxorubicin/ml hydrated beads). For CEUS, a second-generation contrast agent (SonoVue, Bracco, Milan, Italy) and a low mechanical-index technique were used. A part of the tumor was characterized as necrotic if it showed complete lack of enhancement. The percentage of necrosis was calculated at the sonographic section that depicted the largest diameter of the tumor. Differences in the extent of early (2 days after TACE) and delayed (35 to 40 days after TACE) necrosis were quantitatively and subjectively assessed. Early post-TACE tumor necrosis ranged from 21% to 70% (mean 43.5% ± 19%). There was a statistically significant (p = 0.0012, paired Student t test) higher percentage of delayed tumor necrosis, which ranged from 24% to 88% (mean 52.3% ± 20.3%). Subjective evaluation showed a delayed obvious increase of the necrotic areas in 5 patients. In 2 patients, tumor vessels that initially remained patent disappeared on the delayed follow-up. A part of tumor necrosis after chemoembolisation of HCC with DEB seems to take place later than 2 days after TACE. CEUS may provide evidence for the sustained antitumor effect of DEB-TACE. Nevertheless, the ideal time for the imaging evaluation of tumor response remains to be defined.

Evaluation of tumoral enhancement by superparamagnetic iron oxide particles: comparative studies with ferumoxtran and anionic iron oxide nanoparticles

International Nuclear Information System (INIS)

Brillet, P-Y.; Gazeau, F.; Luciani, A.; Bessoud, B.; Cuenod, C.-A.; Siauve, N.; Pons, J.-N.; Poupon, J.; Clement, O.

2005-01-01

This study was designed to compare tumor enhancement by superparamagnetic iron oxide particles, using anionic iron oxide nanoparticles (AP) and ferumoxtran. In vitro, relaxometry and media with increasing complexity were used to assess the changes in r2 relaxivity due to cellular internalization. In vivo, 26 mice with subcutaneously implanted tumors were imaged for 24 h after injection of particles to describe kinetics of enhancement using T1 spin echo, T2 spin echo, and T2 fast spin echo sequences. In vitro, the r2 relaxivity decreased over time (0-4 h) when AP were uptaken by cells. The loss of r2 relaxivity was less pronounced with long (Hahn Echo) than short (Carr-Purcell-Meiboom-Gill) echo time sequences. In vivo, our results with ferumoxtran showed an early T2 peak (1 h), suggesting intravascular particles and a second peak in T1 (12 h), suggesting intrainterstitial accumulation of particles. With AP, the late peak (24 h) suggested an intracellular accumulation of particles. In vitro, anionic iron oxide nanoparticles are suitable for cellular labeling due to a high cellular uptake. Conversely, in vivo, ferumoxtran is suitable for passive targeting of tumors due to a favorable biodistribution. (orig.)

How glyphosate affects plant disease development: it is more than enhanced susceptibility.

Science.gov (United States)

Hammerschmidt, Ray

2018-05-01

Glyphosate has been shown to affect the development of plant disease in several ways. Plants utilize phenolic and other shikimic acid pathway-derived compounds as part of their defense against pathogens, and glyphosate inhibits the biosynthesis of these compounds via its mode of action. Several studies have shown a correlation between enhanced disease and suppression of phenolic compound production after glyphosate. Glyphosate-resistant crop plants have also been studied for changes in resistance as a result of carrying the glyphosate resistance trait. The evidence indicates that neither the resistance trait nor application of glyphosate to glyphosate-resistant plants increases susceptibility to disease. The only exceptions to this are cases where glyphosate has been shown to reduce rust diseases on glyphosate-resistant crops, supporting a fungicidal role for this chemical. Finally, glyphosate treatment of weeds or volunteer crops can cause a temporary increase in soil-borne pathogens that may result in disease development if crops are planted too soon after glyphosate application. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

MR imaging of non-functioning endocrine tumors of the pancreas

International Nuclear Information System (INIS)

Irie, Hiroyuki; Honda, Hiroshi; Kuroiwa, Toshiro

2002-01-01

The purpose of this study was to clarify the MR imaging characteristics of patients with non-functioning endocrine tumors of the pancreas. Fourteen patients with these tumors underwent MR imaging. The signal characteristics of the tumor on T 1 -, T 2 -, and contrast-enhanced T 1 -weighted images were evaluated. The enhancement pattern of the tumor on dynamic study was also examined. The degree of stromal fibrosis was evaluated on the pathologic specimen, and was then classified as mild, moderate, or marked fibrosis. On T 1 -weighted images, the tumors were hypointense in 12 of 14 cases. The signals of the tumors on T 2 -weighted images were varied. The tumors were hypointense in 1 case, isointense in 2 cases, hyperintense in 6 cases, and very hyperintense in the other 5 cases. On contrast-enhanced T 1 -weighted images, the tumors were hyperintense in 8 cases and very hyperintense in 5 cases. On T 2 - and contrast-enhanced T 1 -weighted images, 4 of 5 malignant tumors were very hyperintense. Dynamic study revealed prolonged enhancement in 10 of 11 cases. Pathologic analysis revealed moderate or marked fibrosis in 10 of 14 cases, and prolonged enhancement was considered to be related stromal fibrosis. In conclusion, MR imaging findings of non-functioning endocrine tumors of the pancreas vary in relation to pathological variety. Prolonged enhancement of the tumor on dynamic study is considered to be one of the characteristic MR imaging findings that corresponds to stromal fibrosis of the tumor. (author)

Enhancing Tumor Drug Delivery by Laser-Activated Vascular Barrier Disruption

Science.gov (United States)

2009-12-01

diabetic retinopathy . Therefore, se- lectively targeting existing blood vessels (vascular- disrupting therapy) and/or inhibiting the forma- tion of new...adhesion led to the formation of thrombi that can occlude blood vessels, causing vascular shutdown. However, viable tumor cells were often detected at...tumor sections (Fig. 4). However, viable tumor cells were commonly detected at tumor periphery. Because of the existence of viable peripheral tumor cells

A Systems Genetic Approach to Identify Low Dose Radiation-Induced Lymphoma Susceptibility/DOE2013FinalReport

Energy Technology Data Exchange (ETDEWEB)

Balmain, Allan [University of California, San Francisco; Song, Ihn Young [University of California, San Francisco

2013-05-15

The ultimate goal of this project is to identify the combinations of genetic variants that confer an individual's susceptibility to the effects of low dose (0.1 Gy) gamma-radiation, in particular with regard to tumor development. In contrast to the known effects of high dose radiation in cancer induction, the responses to low dose radiation (defined as 0.1 Gy or less) are much less well understood, and have been proposed to involve a protective anti-tumor effect in some in vivo scientific models. These conflicting results confound attempts to develop predictive models of the risk of exposure to low dose radiation, particularly when combined with the strong effects of inherited genetic variants on both radiation effects and cancer susceptibility. We have used a Systems Genetics approach in mice that combines genetic background analysis with responses to low and high dose radiation, in order to develop insights that will allow us to reconcile these disparate observations. Using this comprehensive approach we have analyzed normal tissue gene expression (in this case the skin and thymus), together with the changes that take place in this gene expression architecture a) in response to low or high- dose radiation and b) during tumor development. Additionally, we have demonstrated that using our expression analysis approach in our genetically heterogeneous/defined radiation-induced tumor mouse models can uniquely identify genes and pathways relevant to human T-ALL, and uncover interactions between common genetic variants of genes which may lead to tumor susceptibility.

Chemotherapy-Induced IL34 Enhances Immunosuppression by Tumor-Associated Macrophages and Mediates Survival of Chemoresistant Lung Cancer Cells.

Science.gov (United States)

Baghdadi, Muhammad; Wada, Haruka; Nakanishi, Sayaka; Abe, Hirotake; Han, Nanumi; Putra, Wira Eka; Endo, Daisuke; Watari, Hidemichi; Sakuragi, Noriaki; Hida, Yasuhiro; Kaga, Kichizo; Miyagi, Yohei; Yokose, Tomoyuki; Takano, Atsushi; Daigo, Yataro; Seino, Ken-Ichiro

2016-10-15

The ability of tumor cells to escape immune destruction and their acquired resistance to chemotherapy are major obstacles to effective cancer therapy. Although immune checkpoint therapies such as anti-PD-1 address these issues in part, clinical responses remain limited to a subpopulation of patients. In this report, we identified IL34 produced by cancer cells as a driver of chemoresistance. In particular, we found that IL34 modulated the functions of tumor-associated macrophages to enhance local immunosuppression and to promote the survival of chemoresistant cancer cells by activating AKT signaling. Targeting IL34 in chemoresistant tumors resulted in a remarkable inhibition of tumor growth when accompanied with chemotherapy. Our results define a pathogenic role for IL34 in mediating immunosuppression and chemoresistance and identify it as a tractable target for anticancer therapy. Cancer Res; 76(20); 6030-42. ©2016 AACR. ©2016 American Association for Cancer Research.

Ganoderma lucidum exerts anti-tumor effects on ovarian cancer cells and enhances their sensitivity to cisplatin.

Science.gov (United States)

Zhao, Sufen; Ye, Gang; Fu, Guodong; Cheng, Jian-Xin; Yang, Burton B; Peng, Chun

2011-05-01

Ganoderma lucidum is a herbal mushroom known to have many health benefits, including the inhibition of tumor cell growth. However, the effect of Ganoderma lucidum on epithelial ovarian cancer (EOC), the most fatal gynecological malignancy, has not yet been reported. In this study, we determined whether Ganoderma lucidum regulates EOC cell activity. Using several cell lines derived from EOC, we found that Ganoderma lucidum strongly decreased cell numbers in a dose-dependent manner. Ganoderma lucidum also inhibited colony formation, cell migration and spheroid formation. In particular, Ganoderma lucidum was effective in inhibiting cell growth in both chemosensitive and chemoresistant cells and the treatment with Ganoderma lucidum significantly enhanced the effect of cisplatin on EOC cells. Furthermore, Ganoderma lucidum induced cell cycle arrest at the G2/M phase and also induced apoptosis by activating caspase 3. Finally, Ganoderma lucidum increased p53 but inhibited Akt expression. Taken together, these findings suggest that Ganoderma lucidum exerts multiple anti-tumor effects on ovarian cancer cells and can enhance the sensitivity of EOC cells to cisplatin.

Multisite tumor sampling enhances the detection of intratumor heterogeneity at all different temporal stages of tumor evolution.

Science.gov (United States)

Erramuzpe, Asier; Cortés, Jesús M; López, José I

2018-02-01

Intratumor heterogeneity (ITH) is an inherent process of tumor development that has received much attention in previous years, as it has become a major obstacle for the success of targeted therapies. ITH is also temporally unpredictable across tumor evolution, which makes its precise characterization even more problematic since detection success depends on the precise temporal snapshot at which ITH is analyzed. New and more efficient strategies for tumor sampling are needed to overcome these difficulties which currently rely entirely on the pathologist's interpretation. Recently, we showed that a new strategy, the multisite tumor sampling, works better than the routine sampling protocol for the ITH detection when the tumor time evolution was not taken into consideration. Here, we extend this work and compare the ITH detections of multisite tumor sampling and routine sampling protocols across tumor time evolution, and in particular, we provide in silico analyses of both strategies at early and late temporal stages for four different models of tumor evolution (linear, branched, neutral, and punctuated). Our results indicate that multisite tumor sampling outperforms routine protocols in detecting ITH at all different temporal stages of tumor evolution. We conclude that multisite tumor sampling is more advantageous than routine protocols in detecting intratumor heterogeneity.

Linear and nonlinear optical susceptibilities in a laterally coupled quantum-dot–quantum-ring system

International Nuclear Information System (INIS)

Zeng, Zaiping; Garoufalis, Christos S.; Baskoutas, Sotirios

2014-01-01

Linear and nonlinear optical susceptibilities in a laterally coupled quantum-dot–quantum-ring system have been theoretically studied. In general, we find that the structure parameters of the coupled system significantly affect the optical susceptibilities. The enhancement of the coupling effects between the dot and ring is found to increase considerably the optical susceptibilities and redshift drastically the transition energies. Comparing to the linear susceptibility, the nonlinear optical susceptibility is found to be more sensitive to the variation of the structure parameters. A comprehensive analysis of the electron probability density movement with respect to the modification of the structure parameters is provided, which offers a unique perspective of the ground-state localization. - Highlights: • Optical susceptibilities in a quantum-dot–quantum-ring system are studied. • The structure parameters significantly affect the optical susceptibilities. • The enhancement of the coupling effects increases the optical susceptibilities. • The nonlinear susceptibility is more sensitive to the change in structure parameters. • A comprehensive analysis of the electron probability density movement is provided

Optimal gadolinium dose level for magnetic resonance imaging (MRI) contrast enhancement of U87-derived tumors in athymic nude rats for the assessment of photodynamic therapy

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Cross, Nathan; Varghai, Davood; Flask, Chris A.; Feyes, Denise K.; Oleinick, Nancy L.; Dean, David

2009-02-01

This study aims to determine the effect of varying gadopentetate dimeglumine (Gd-DTPA) dose on Dynamic Contrast Enhanced-Magnetic Resonance Imaging (DCE-MRI) tracking of brain tumor photodynamic therapy (PDT) outcome. Methods: We injected 2.5 x 105 U87 cells (derived from human malignant glioma) into the brains of six athymic nude rats. After 9, 12, and 13 days DCE-MRI images were acquired on a 9.4 T micro-MRI scanner before and after administration of 100, 150, or 200 μL of Gd-DTPA. Results: Tumor region normalized DCE-MRI scan enhancement at peak was: 1.217 over baseline (0.018 Standard Error [SE]) at the 100 μL dose, 1.339 (0.013 SE) at the 150 μL dose, and 1.287 (0.014 SE) at the 200 μL dose. DCE-MRI peak tumor enhancement at the 150 μL dose was significantly greater than both the 100 μL dose (p DTPA dose provided the greatest T1 weighted contrast enhancement, while minimizing negative T2* effects, in DCE-MRI scans of U87-derived tumors. Maximizing Gd-DTPA enhancement in DCE-MRI scans may assist development of a clinically robust (i.e., unambiguous) technique for PDT outcome assessment.

Measurement of magnetic susceptibility on tailings cores report on cores obtained from the Ontario Research Foundation lysimeter experiment

International Nuclear Information System (INIS)

1984-10-01

Bulk susceptibility and induced magnetic remanence results are reported for 40 cores obtained from the uranium tailings lysimeter experiment at the Ontario Research Foundation. Both methods indicate a broad threefold subdivision of the tailings pile. An upper zone is characterized by an enhanced susceptibility level, which is related to enhanced concentration of both magnetite and hematite. Depletion zones, where present, are of limited areal extent and strongly developed. An intermediate zone is characterized by a mixture of large areas of reduced susceptibility that separate smaller regions of slightly enhanced susceptibility. The zones of susceptibility depletion appear to define a dendritic drainage pattern. Locally in this zone magnetite is enhanced and hematite depleted. In the lowermost zone susceptibility levels are reduced over most of the tailings bed. Only in the upper most right hand corner is there any vestige of a positive susceptibility concentration. Both magnetite and hematite are strongly depleted in this lower zone. Visually it is apparent that this lowermost depleted zone correlates to the zones of strongest 'yellowcake' development

The association between miR-499 polymorphism and cancer susceptibility: a meta-analysis.

Science.gov (United States)

Xu, Zhongfei; Zhang, Enjiao; Duan, Weiyi; Sun, Changfu; Bai, Shuang; Tan, Xuexin

2015-01-01

MicroRNAs are a class of new noncoding RNA that play important roles in the pathogenesis of tumor. Rs3746444 in miR-499 is suggested to be associated with cancer susceptibility. In the present study, we assess the association between miR-499 rs3746444 polymorphism and cancer susceptibility through a meta-analysis. We searched relevant articles from the PubMed and Embase databases. We screened all the resulting articles for adherence to the inclusion and exclusion criteria. The associations between miR-499 polymorphism and cancer susceptibility were estimated by computing the odds ratios (ORs) and 95% confidence intervals (CIs). All analyses were performed using Stata software. There are 18 datasets included in the analysis. Statistically significant associations were found between the miR-499 rs3746444 polymorphism and susceptibility to cancer (GG versus AA: OR =1.24, 95% CI: 1.01-1.52; G versus A: OR =1.11, 95% CI: 1.01-1.23). A subsequent analysis, on the basis of ethnicity for the population characteristic, showed that Asians had increased susceptibility to cancer (GG versus AA: OR =1.32, 95% CI: 1.09-1.59; GG + AG versus AA: OR = 1.17, 95% CI: 1.01-1.37). In the subgroup analysis of tumor type, none of the genetic models had statistically significant results. The meta-regression suggested that race and cancer types are not the source of heterogeneity in the present meta-analysis. No publication bias was detected by either the inverted funnel plot or Egger's test. Rs3746444 in miR-499 might be related to susceptibility to cancer.

Use of Ultrasmall Superparamagnetic Iron Oxide Enhanced Susceptibility Weighted Imaging and Mean Vessel Density Imaging to Monitor Antiangiogenic Effects of Sorafenib on Experimental Hepatocellular Carcinoma

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Shuohui Yang

2017-01-01

Full Text Available We investigated effectiveness of ultrasmall superparamagnetic iron oxide enhanced susceptibility weighted imaging (USPIO-enhanced SWI and mean vessel density imaging (Q in monitoring antiangiogenic effects of Sorafenib on orthotopic hepatocellular carcinoma (HCC. Thirty-five HCC xenografts were established. USPIO-enhanced SWI and Q were performed on a 1.5 T MR scanner at baseline, 7, 14, and 21 days after Sorafenib treatment. Intratumoral susceptibility signal intensity (ITSS and Q were serially measured and compared between the treated (n = 15 and control groups (n = 15. Both ITSS and Q were significantly lower in the treated group at each time point (P < 0.05. Measurements in the treated group showed that ITSS persisted at 7 days (P = 0.669 and increased at 14 and 21 days (P < 0.05, while Q significantly declined at 7 days (P = 0.028 and gradually increased at 14 and 21 days. In the treated group, significant correlation was found between Q and histologic microvessel density (MVD (r = 0.753, P < 0.001, and ITSS correlated well with MVD (r = 0.742, P = 0.002 after excluding the data from baseline. This study demonstrated that USPIO-enhanced SWI and Q could provide novel biomarkers for evaluating antiangiogenic effects of Sorafenib on HCC.

Inhibition of c-Jun N-terminal kinase sensitizes tumor cells to flavonoid-induced apoptosis through down-regulation of JunD

International Nuclear Information System (INIS)

Kook, Sung-Ho; Son, Young-Ok; Jang, Yong-Suk; Lee, Kyung-Yeol; Lee, Seung-Ah; Kim, Beom-Soo; Lee, Hyun-Jeong; Lee, Jeong-Chae

2008-01-01

Reduction of susceptibility to apoptosis signals is a crucial step in carcinogenesis. Therefore, sensitization of tumor cells to apoptosis is a promising therapeutic strategy. c-Jun NH 2 -terminal kinase (JNK) has been implicated in stress-induced apoptosis. However, many studies also emphasize the role of JNK on cell survival, although its mechanisms are not completely understood. Previously, we found that inhibition of JNK activity promotes flavonoid-mediated apoptosis of human osteosarcoma cells. We thus determined whether inhibition of JNK sensitizes tumor cells to a bioflavonoid-induced apoptosis, and whether this effect of JNK is a general effect. As the results, quercetin and genistein as well as a flavonoid fraction induced apoptosis of tumor cells, which was further accelerated by specific JNK inhibitor, SP600125 or by small interfering RNA specific to JNK1/2. This effect was specific to types of cells because it was further apparent in tumorigenic cell lines. Inhibition of JNK by SP600125 also reduced flavonoid-stimulated nuclear induction of JunD which was known to have protective role in apoptosis, whereas JNK inhibition alone had little effect on apoptosis. The flavonoid-induced apoptosis of tumor cells was significantly enhanced by transfecting them with antisense JunD oligonucleotides. These results suggest that inhibition of JNK facilitates flavonoid-induced apoptosis through down-regulation of JunD, which is further sensitive to tumor cells. Therefore, combination with a specific JNK inhibitor further enhances the anti-cancer and chemopreventive potential of bio-flavonoids

Assessment of MRI and dynamic contrast-enhanced MRI in the differential diagnosis of adenomatoid odontogenic tumor

International Nuclear Information System (INIS)

Asaumi, Jun-ichi; Yanagi, Yoshinobu; Konouchi, Hironobu; Hisatomi, Miki; Matsuzaki, Hidenobu; Shigehara, Hiroshi; Kishi, Kanji

2004-01-01

The radiographical differentiation of adenomatoid odontogenic tumor (AOT) from dentigerous cysts, calcifying odontogenic cysts, calcifying epithelial odontogenic tumors, odontogenic keratocysts and amelobastomas is sometimes difficult. We attempted to differentiate AOT from other lesions similar to AOT in radiographic findings using MRI. The MRI features of AOT in our three cases included homogeneous low SI in the cystic portion and homogeneous intermediate SI in the solid portion on T1WI, homogeneous high SI in the cystic portion and intermediate to slightly high SI in the solid portion on T2WI and enhancement of only the solid portion on CE-T1WI although none of the sequences included SI of calcifications. The contrast index curves in the three cases of AOT showed a gradual increase to 300 s, which signified a benign tumor. These MRI features were characteristic features of AOT and might be a basis for differentiating AOT from the above possible lesions in radiographic examinations

Theoretical evaluations of magnetic nanoparticle-enhanced heating on tumor embedded with large blood vessels during hyperthermia

International Nuclear Information System (INIS)

Wang, Q.; Deng, Z. S.; Liu, J.

2012-01-01

The large blood vessels surrounding the tumor would significantly result in heat sink, and thus seriously limit the thermal ablative area during tumor hyperthermia. Magnetic nanoparticle (MNP) was recently identified as an important heating enhancer to improve the treatment efficiency. It will not only help to absorb more energy under the irradiation of external magnetic field, but also can block the blood flow and subsequently weaken the heat sink effect of large vessels. In this study, these two critical factors, reserved to be undisclosed before in theory, were comprehensively investigated through three-dimensional numerical simulation. The results suggested that concerning the contribution to temperature increase in the tissues surrounding large vessel, the factor of blood flow blocking is more effective than that of energy absorption. Therefore, selective loading of MNPs to the target sites is expected to serve as a promising method to perform successful hyperthermia treatment for tumor tissues embedded with large blood vessels.

Theoretical evaluations of magnetic nanoparticle-enhanced heating on tumor embedded with large blood vessels during hyperthermia

Energy Technology Data Exchange (ETDEWEB)

Wang, Q. [Tsinghua University, Department of Biomedical Engineering, School of Medicine (China); Deng, Z. S. [Chinese Academy of Sciences, Key Laboratory of Cryogenics, Technical Institute of Physics and Chemistry (China); Liu, J., E-mail: jliubme@tsinghua.edu.cn [Tsinghua University, Department of Biomedical Engineering, School of Medicine (China)

2012-07-15

The large blood vessels surrounding the tumor would significantly result in heat sink, and thus seriously limit the thermal ablative area during tumor hyperthermia. Magnetic nanoparticle (MNP) was recently identified as an important heating enhancer to improve the treatment efficiency. It will not only help to absorb more energy under the irradiation of external magnetic field, but also can block the blood flow and subsequently weaken the heat sink effect of large vessels. In this study, these two critical factors, reserved to be undisclosed before in theory, were comprehensively investigated through three-dimensional numerical simulation. The results suggested that concerning the contribution to temperature increase in the tissues surrounding large vessel, the factor of blood flow blocking is more effective than that of energy absorption. Therefore, selective loading of MNPs to the target sites is expected to serve as a promising method to perform successful hyperthermia treatment for tumor tissues embedded with large blood vessels.

Multimodality functional imaging of spontaneous canine tumors using 64CU-ATSM and 18FDG PET/CT and dynamic contrast enhanced perfusion CT

DEFF Research Database (Denmark)

Hansen, Anders E; Kristensen, Annemarie T; Law, Ian

2012-01-01

To compare the distribution and uptake of the hypoxia tracer (64)Cu-diacetyl-bis(N(4)-methylthiosemicarbazone) ((64)Cu-ATSM) PET/CT, FDG PET/CT and dynamic contrast enhanced perfusion CT (DCE-pCT) in spontaneous canine tumors. In addition (64)Cu-ATSM distribution over time was evaluated.......To compare the distribution and uptake of the hypoxia tracer (64)Cu-diacetyl-bis(N(4)-methylthiosemicarbazone) ((64)Cu-ATSM) PET/CT, FDG PET/CT and dynamic contrast enhanced perfusion CT (DCE-pCT) in spontaneous canine tumors. In addition (64)Cu-ATSM distribution over time was evaluated....

PET imaging of 64Cu-DOTA-scFv-anti-PSMA lipid nanoparticles (LNPs): Enhanced tumor targeting over anti-PSMA scFv or untargeted LNPs

International Nuclear Information System (INIS)

Wong, Patty; Li, Lin; Chea, Junie; Delgado, Melissa K.; Crow, Desiree; Poku, Erasmus; Szpikowska, Barbara; Bowles, Nicole; Channappa, Divya; Colcher, David; Wong, Jeffrey Y.C.; Shively, John E.; Yazaki, Paul J.

2017-01-01

Introduction: Single chain (scFv) antibodies are ideal targeting ligands due to their modular structure, high antigen specificity and affinity. These monovalent ligands display rapid tumor targeting but have limitations due to their fast urinary clearance. Methods: An anti-prostate membrane antigen (PSMA) scFv with a site-specific cysteine was expressed and evaluated in a prostate cancer xenograft model by Cu-64 PET imaging. To enhance tumor accumulation, the scFv-cys was conjugated to the co-polymer DSPE-PEG-maleimide that spontaneously assembled into a homogeneous multivalent lipid nanoparticle (LNP). Results: The targeted LNP exhibited a 2-fold increase in tumor uptake compared to the scFv alone using two different thiol ester chemistries. The anti-PSMA scFv-LNP exhibited a 1.6 fold increase in tumor targeting over the untargeted LNP. Conclusions: The targeted anti-PSMA scFv-LNP showed enhanced tumor accumulation over the scFv alone or the untargeted DOTA-micelle providing evidence for the development of this system for drug delivery. Advances in knowledge and implications for patient care: Anti-tumor scFv antibody fragments have not achieved their therapeutic potential due to their fast blood clearance. Conjugation to an LNP enables multivalency to the tumor antigen as well as increased molecular size for chemotherapy drug delivery.

Liposome accumulation in irradiated tumors display important tumor and dose dependent differences

DEFF Research Database (Denmark)

Hansen, Anders Elias; Fliedner, Frederikke Petrine; Henriksen, Jonas Rosager

2018-01-01

Radiation therapy may affect several important parameters in the tumor microenvironment and thereby influence the accumulation of liposomes by the enhanced permeability and retention (EPR)-effect. Here we investigate the effect of single dose radiation therapy on liposome tumor accumulation by PET...

Global stability of a susceptible-infected-susceptible epidemic model on networks with individual awareness

International Nuclear Information System (INIS)

Li Ke-Zan; Xu Zhong-Pu; Zhu Guang-Hu; Ding Yong

2014-01-01

Recent research results indicate that individual awareness can play an important influence on epidemic spreading in networks. By local stability analysis, a significant conclusion is that the embedded awareness in an epidemic network can increase its epidemic threshold. In this paper, by using limit theory and dynamical system theory, we further give global stability analysis of a susceptible-infected-susceptible (SIS) epidemic model on networks with awareness. Results show that the obtained epidemic threshold is also a global stability condition for its endemic equilibrium, which implies the embedded awareness can enhance the epidemic threshold globally. Some numerical examples are presented to verify the theoretical results. (interdisciplinary physics and related areas of science and technology)

Susceptibility-weighted imaging in stroke-like migraine attacks after radiation therapy syndrome

Energy Technology Data Exchange (ETDEWEB)

Khanipour Roshan, Sara; Salmela, Michael B.; McKinney, Alexander M. [University Of Minnesota, Department of Radiology, Division of Neuroradiology, Minneapolis, MN (United States)

2015-11-15

Stroke-like migraine attacks after radiation therapy (SMART) syndrome has a characteristic clinical presentation and postcontrast T1WI MRI appearance. Susceptibility-weighted imaging (SWI) may help distinguish SMART from other disorders that may have a similar postcontrast MRI appearance. The MRI examinations of four patients with SMART syndrome are described herein, each of which included SWI, FLAIR, DWI, and postcontrast T1WI on the presenting and follow-up MRI examinations. In each, the initial SWI MRI demonstrated numerous susceptibility hypointensities <5 mm in size throughout the cerebrum, particularly within the periventricular white matter (PVWM), presumably related to radiation-induced cavernous hemangiomas (RICHs). By follow-up MRI, each postcontrast examination had demonstrated resolution of the gyriform enhancement on T1WI, without susceptibility hypointensities on SWI within those previously enhancing regions. These preliminary findings suggest that SWI may help identify SMART syndrome or at least help discriminate it from other disorders, by the findings of numerous susceptibility hypointensities on SWI likely representing RICHs, gyriform enhancement on T1WI, and postsurgical findings or appropriate clinical history. (orig.)

Ionizing radiation enhances immunogenicity of cells expressing a tumor-specific T-cell epitope

International Nuclear Information System (INIS)

Ciernik, Ilja F.; Romero, Pedro; Berzofsky, Jay A.; Carbone, David P.

1999-01-01

Background: p53 point mutations represent potential tumor-specific cytolytic T lymphocyte (CTL) epitopes. Whether ionizing radiation (IR) alters the immunological properties of cells expressing mutant p53 in respect of the CTL epitope generated by a defined point mutation has not been evaluated. Methods: Mutant p53-expressing syngeneic, nontumor forming BALB/c 3T3 fibroblasts, tumor forming ras-transfected BALB/c 3T3 sarcomas, and DBA/2-derived P815 mastocytoma cells, which differ at the level of minor histocompatibility antigens, were used as cellular vaccines. Cells were either injected with or without prior IR into naive BALB/c mice. Cellular cytotoxicity was assessed after secondary restimulation of effector spleen cells in vitro. Results: Injection of P815 mastocytoma cells expressing the mutant p53 induced mutation-specific CTL in BALB/c mice irrespective of prior irradiation. However, syngeneic fibroblasts or fibrosarcomas endogenously expressing mutant p53 were able to induce significant mutation-specific CTL only when irradiated prior to injection into BALB/c mice. IR of fibroblasts did not detectably alter the expression of cell surface molecules involved in immune response induction, nor did it alter the short-term in vitro viability of the fibroblasts. Interestingly, radioactively-labeled fibroblasts injected into mice after irradiation showed altered organ distribution, suggesting that the in vivo fate of these cells may play a crucial role in their immunogenicity. Conclusions: These findings indicate that IR can alter the immunogenicity of syngeneic normal as well as tumor forming fibroblasts in vivo, and support the view that ionizing radiation enhances immunogenicity of cellular tumor vaccines

Gold nanorod-mediated hyperthermia enhances the efficacy of HPMA copolymer-90Y conjugates in treatment of prostate tumors

International Nuclear Information System (INIS)

Buckway, Brandon; Frazier, Nick; Gormley, Adam J.; Ray, Abhijit; Ghandehari, Hamidreza

2014-01-01

Introduction: The treatment of prostate cancer using a radiotherapeutic 90 Y labeled N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer can be enhanced with localized tumor hyperthermia. An 111 In labeled HPMA copolymer system for single photon emission computerized tomography (SPECT) was developed to observe the biodistribution changes associated with hyperthermia. Efficacy studies were conducted in prostate tumor bearing mice using the 90 Y HPMA copolymer with hyperthermia. Methods: HPMA copolymers containing 1, 4, 7, 10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) were synthesized by reversible addition-fragmentation transfer (RAFT) copolymerization and subsequently labeled with either 111 In for imaging or 90 Y for efficacy studies. Radiolabel stability was characterized in vitro with mouse serum. Imaging and efficacy studies were conducted in DU145 prostate tumor bearing mice. Imaging was performed using single photon emission computerized tomography (SPECT). Localized mild tumor hyperthermia was achieved by plasmonic photothermal therapy using gold nanorods. Results: HPMA copolymer-DOTA conjugates demonstrated efficient labeling and stability for both radionuclides. Imaging analysis showed a marked increase of radiolabeled copolymer within the hyperthermia treated prostate tumors, with no significant accumulation in non-targeted tissues. The greatest reduction in tumor growth was observed in the hyperthermia treated tumors with 90 Y HPMA copolymer conjugates. Histological analysis confirmed treatment efficacy and safety. Conclusion: HPMA copolymer-DOTA conjugates radiolabeled with both the imaging and treatment radioisotopes, when combined with hyperthermia can serve as an image guided approach for efficacious treatment of prostate tumors

Identification of tomato introgression lines with enhanced susceptibility or resistance to infection by parasitic giant dodder (Cuscuta reflexa).

Science.gov (United States)

Krause, Kirsten; Johnsen, Hanne R; Pielach, Anna; Lund, Leidulf; Fischer, Karsten; Rose, Jocelyn K C

2018-02-01

The parasitic flowering plant genus Cuscuta (dodder) is a parasitic weed that infects many important crops. Once it winds around the shoots of potential host plants and initiates the development of penetration organs, called haustoria, only a few plant species have been shown to deploy effective defense mechanisms to ward off Cuscuta parasitization. However, a notable exception is Solanum lycopersicum (tomato), which exhibits a local hypersensitive reaction when attacked by giant dodder (Cuscuta reflexa). Interestingly, the closely related wild desert tomato, Solanum pennellii, is unable to stop the penetration of its tissue by the C. reflexa haustoria. In this study, we observed that grafting a S. pennellii scion onto the rootstock of the resistant S. lycopersicum did not change the susceptibility phenotype of S. pennellii. This suggests that hormones, or other mobile substances, produced by S. lycopersicum do not induce a defense reaction in the susceptible tissue. Screening of a population of introgression lines harboring chromosome fragments from S. pennellii in the genome of the recurrent parent S. lycopersicum, revealed that most lines exhibit the same defense reaction as shown by the S. lycopersicum parental line. However, several lines showed different responses and exhibited either susceptibility, or cell death that extended considerably beyond the infection site. These lines will be valuable for the future identification of key loci involved in the perception of, and resistance to, C. reflexa and for developing strategies to enhance resistance to infection in crop species. © 2017 Scandinavian Plant Physiology Society.

Characterization of tumor heterogeneity using dynamic contrast enhanced CT and FDG-PET in non-small cell lung cancer

International Nuclear Information System (INIS)

Elmpt, Wouter van; Das, Marco; Hüllner, Martin; Sharifi, Hoda; Zegers, Catharina M.L.; Reymen, Bart; Lambin, Philippe; Wildberger, Joachim E.; Troost, Esther G.C.; Veit-Haibach, Patrick; De Ruysscher, Dirk

2013-01-01

Purpose: Dynamic contrast-enhanced CT (DCE-CT) quantifies vasculature properties of tumors, whereas static FDG-PET/CT defines metabolic activity. Both imaging modalities are capable of showing intra-tumor heterogeneity. We investigated differences in vasculature properties within primary non-small cell lung cancer (NSCLC) tumors measured by DCE-CT and metabolic activity from FDG-PET/CT. Methods: Thirty three NSCLC patients were analyzed prior to treatment. FDG-PET/CT and DCE-CT were co-registered. The tumor was delineated and metabolic activity was segmented on the FDG-PET/CT in two regions: low (<50% maximum SUV) and high (⩾50% maximum SUV) metabolic uptake. Blood flow, blood volume and permeability were calculated using a maximum slope, deconvolution algorithm and a Patlak model. Correlations were assessed between perfusion parameters for the regions of interest. Results: DCE-CT provided additional information on vasculature and tumor heterogeneity that was not correlated to metabolic tumor activity. There was no significant difference between low and high metabolic active regions for any of the DCE-CT parameters. Furthermore, only moderate correlations between maximum SUV and DCE-CT parameters were observed. Conclusions: No direct correlation was observed between FDG-uptake and parameters extracted from DCE-CT. DCE-CT may provide complementary information to the characterization of primary NSCLC tumors over FDG-PET/CT imaging

Analysis on CT features of tumor-like gastric schwannomas