bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3932: High resolution imaging mass spectrometry reveals the breast cancer cell-related profiles of phosphatidylinositol unsaturation.
Authors: Kawashima Masahiro , Iwamoto Noriko , Kawaguchi-Sakita Nobuko , Sugimoto Masahiro , Ueno Takayuki , Terasawa Kazuya , Sato Taka-Aki , Tanaka Koichi , Shimizu Kazuharu , Toi Masakazu 
Published: August 2014

Abstract
Lipid metabolism is supposed to be altered in breast cancer, and several literatures have suggested the possible compositional change of phospholipids in breast cancer tissues and its correlations with the tumor grade, sex hormone receptor status and patient's prognosis. However, the breast cancer cell-related alteration of phospholipid profiles and its underlying metabolic change remain unclear. The aim of this study is to investigate the cancer cell-related phospholipid alteration by using high resolution matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS). We evaluated the spatial distributions and the proportions of phosphatidylinositols (PIs) in seven breast cancer tissues (three luminal cases and four non-luminal cases including one Her2 positive case) and one normal breast tissue. MS images of PIs and their mass spectra showed that the fatty acyl chain compositions of observed PIs remarkably changed in cancer cell region, compared with those in normal duct epithelium or surrounding stromal cells. PIs containing polyunsaturated fatty acid (PUFA) were the major components in normal duct epithelium. In five of seven cancer cases, PIs containing monounsaturated fatty acid (MUFA) were the most dominant in the observed PIs and specifically upregulated in cancer cells. In the rest of the cases, the MUFA upregulation was less obvious than the aforementioned five cases, and PIs containing PUFA still constituted a large percentage of observed PIs. In non-luminal cases, the MUFA upregulation in cancer cells was well correlated with the expression level of stearoyl CoA desaturase 1 (SCD1), a key enzyme in de novo MUFA synthesis. This observation suggested that the upregulation of de novo MUFA synthesis in cancer cells could contribute to the increase of PIs containing MUFA. In conclusion, high resolution MALDI-IMS revealed the breast cancer cell-related changes of PI profiles according to the degree of the fatty acyl chain unsaturation, which implied the existence of cancer cell-related PI remodeling process.
Citation Format: Masahiro Kawashima, Noriko Iwamoto, Nobuko Kawaguchi-Sakita, Masahiro Sugimoto, Takayuki Ueno, Kazuya Terasawa, Taka-Aki Sato, Koichi Tanaka, Kazuharu Shimizu, Masakazu Toi. High resolution imaging mass spectrometry reveals the breast cancer cell-related profiles of phosphatidylinositol unsaturation. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3932. doi:10.1158/1538-7445.AM2013-3932
Abstract 3938: Role of Chi3l1/YKL-40 in the tumor progression and metastasis in the lung.
Authors: Lee Chun Geun , Ma Bing , Koo Ja Seok , Herbst Roy S. , Elias Jack A. 
Published: August 2014

Abstract
The 18 glycosyl hydrolase gene family (GH18) contains chitinases and chitinase-like proteins (CLP) that lack enzyme activity. Chitinase 3-like-1 (Chi3l1; also called BRP-39 in mouse and YKL-40 in man), the prototypic CLP, is expressed in an exaggerated fashion in the serum and or tissues from patients with a variety of malignancies including breast, colon/rectum, ovary, melanoma, prostate, kidney, brain, bone, and lung. In many of these malignancies, there is a strong correlation between the levels of Chi3l1/YKL-40 and disease progression, prognosis and disease-free survival. However, the roles of YKL-40 in the development and progression of lung cancer has not been determined. To begin to address this issue, we generated Chi3l1/BRP-39 null mutant (Chi3l1-/-) and lung-specific overexpressing YKL-40 transgenic (YKL-40 Tg) mice and evaluated them in a number of settings. The studies demonstrated that Chi3l1/BRP-39/YKL-40 is an important regulator of cellular apoptosis, inflammation, angiogenesis and M2 macrophage differentiation. We also found that melanoma metastasis to the lung was significantly decreased in Chi3l1-/- mice and increased in YKL-40 Tg mice and that activation of the RIG-like helicase (RLH) innate immune pathway significantly decreased BRP-39 production and melanoma or breast cancer lung metastasis. Lastly, immunohistochemical (IHC) analysis demonstrated that, in mice with specific mutation of KRAS and/or p53, Chi3l1/BRP-39 is expressed in an exaggerated manner in normal peritumor tissues and lung cancer cells in early and late stages of lung cancer development, respectively. In combination, our preliminary studies demonstrate that Chi3l1/BRP-39/YKL-40 plays a critical role in the generation of a metastasis-permissive microenvironment and is dysregulated in the course of the development of primary lung cancers.
Citation Format: Chun Geun Lee, Bing Ma, Ja Seok Koo, Roy S. Herbst, Jack A. Elias. Role of Chi3l1/YKL-40 in the tumor progression and metastasis in the lung. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3938. doi:10.1158/1538-7445.AM2013-3938
Abstract 3939: The collagen receptor discoidin domain receptor 2 facilitates breast cancer metastasis by stabilizing Snail1 protein.
Authors: Zhang Kun , Corsa Callie , Prior Julie , Piwnica-Worms David , Longmore Gregory D. 
Published: August 2014

Abstract
Mammographic density is a leading risk factor for the development of breast cancer and these cancers are more invasive and metastatic. The increase in breast density is, in part, due to increased fibrillar collagen deposition. In an RNAi human kinome screen to identify post-transcriptional regulators of Snail1 protein stability we found the collagen receptor DDR2, but not related DDR1, to stabilize Snail1 protein as a result of collagen I activated DDR2 stimulation of ERK2 activity. This can occur independent of β1-integrin and TGFβ signals. DDR2 is not required for TGFβ-induced Epithelial Mesenchymal transition (EMT) or EMT-induced Snail1 transcription. Rather DDR2 expression, which is absent in normal breast epithelia, is induced during EMT as breast tumor cells assume invasive, mesenchymal features. DDR2-induced ERK2 activity stabilizes Snail1 protein level in two ways. First, ERK2 interacts with and phosphorylates Snail1 and second ERK2 inhibits GSK3b.
DDR2 was found to be critical for breast cancer cell invasion and migration in vitro, in 3D collagen gels, and breast cancer metastasis in vivo, in syngeneic xenograft models. A majority of human invasive ductal breast carcinomas express DDR2 protein and there is a strong association between nuclear Snail1 expression, DDR2 expression, and the absence of E-cadherin expression. The small group of breast cancer patients with tumors harboring increased DDR2 gene copy number has diminished survival. We propose that DDR2 acts in a positive feedback loop to maintain Snail1 protein level and activity in breast tumor cells at the leading, invasive edge where tumor cells that have undergone EMT and invaded through the basement membrane to encounter extracellular matrix collagen I. This facilitates the continued tumor cell invasion and migration through the collagen I-rich ECM, and thereby, contributes to breast cancer metastasis.
That the collagen I receptor DDR2 maintains the EMT-inducing Snail1 protein level and activity and contributes to breast cancer metastasis could explain the increase in metastasis of breast cancers in women with dense breasts. As such, DDR2 could be considered a novel RTK target for the treatment of breast cancer metastasis.
Citation Format: Kun Zhang, Callie Corsa, Julie Prior, David Piwnica-Worms, Gregory D. Longmore. The collagen receptor discoidin domain receptor 2 facilitates breast cancer metastasis by stabilizing Snail1 protein. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3939. doi:10.1158/1538-7445.AM2013-3939
Abstract 3944: Serine phosphorylation of vasodilator-stimulated phosphoprotein regulates the tumorigenic potential of colon cancer cells.
Authors: Ali Mehboob , Chervoneva Inna , Pitari Giovanni M. 
Published: August 2014

Abstract
Colorectal cancer is one of the most common and deadly cancers in developed nations. Molecular mechanisms precisely defining colorectal tumorigenesis and cancer progression remain unclear, an obstacle for innovative research applications. The vasodilator-stimulated phosphoprotein (VASP) is an actin-binding protein which critically regulates the cytoskeleton and its dependent functions, including cell shape, adhesion and migration. Of relevance, VASP Ser phosphorylation becomes deregulated in colorectal transformation and promotes invasive protrusion dynamics. Here, VASP Ser phosphorylation was selectively inhibited in colon carcinoma cells employing dominant negative mutants. Effects on cell tumorigenic potential were examined with two mouse models of colorectal cancer. Compared to control conditions, suppression of VASP Ser239 phosphorylation resulted in an enhanced cancer cell capability to establish tumor colonies in both the subcutaneous and peritoneal xenograft model. Increased tumorigenicity reflected, in part, hyper proliferative kinetics of cancer cells bearing VASP Ser239 mutants, which exhibited accelerated growth and DNA synthesis rates. In contrast, selective inhibition of VASP Ser157 slowed cell proliferation and reduced the in vivo tumorigenic potential of colon carcinoma cells, compared to respective controls. These observations support the suggestion that VASP Ser phosphorylation represents a fine signaling mechanism to control intestinal tumorigenesis and invasion, a novel paradigm for targeted anticancer strategies in patients with colorectal cancer.
Citation Format: Mehboob Ali, Inna Chervoneva, Giovanni M. Pitari. Serine phosphorylation of vasodilator-stimulated phosphoprotein regulates the tumorigenic potential of colon cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3944. doi:10.1158/1538-7445.AM2013-3944
Abstract 3950: Extracellular protons promote the metastasis of breast cancer via activation of the proton-sensing receptor G-protein coupled receptor 4.
Authors: Lee Yu Jin , Heo Kyun , Park Soo-Ah , Noh Dong-Young , Kim Kyong-Tai , Ryu Sung Ho , Suh Pann-Ghill Suh 
Published: August 2014

Abstract
Acidosis of the tumor microenvironment is a typical malignant phenotype that enhances tumorigenesis and tumor progression induced by altered cellular signaling and transcriptional regulation. However, the underlying mechanism by which tumor cells sense and response the acidic environment remains unclear. In this study, we found that expression of G-protein coupled receptor (GPR4) was upregulated in breast cancer cells and tissues from patients with breast cancer compared to normal breast cells and tissues. In a xenograft mouse model, short hairpin RNA (shRNA)-mediated silencing of endogenous GPR4 significantly reduced distant metastases to several lymph nodes and the lung compared to control shRNA. In addition, endogenous GPR4 expression in breast cancer cells enhanced tumor cell migration and invasion in an acidic environment and induced the activation of RhoA and extracellular signal-regulated kinase (ERK) pathway. Acidosis/GPR4 activation also upregulated the expression of matrix metalloproteinase-9 (MMP9) and vascular endothelial growth factor (VEGF) in breast cancer cells. These findings highlight a novel mechanism by which acidosis-mediated tumor aggressiveness is acquired as a critical step for distant metastasis in breast cancer.
Citation Format: Yu Jin Lee, Kyun Heo, Soo-Ah Park, Dong-Young Noh, Kyong-Tai Kim, Sung Ho Ryu, Pann-Ghill Suh Suh. Extracellular protons promote the metastasis of breast cancer via activation of the proton-sensing receptor G-protein coupled receptor 4. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3950. doi:10.1158/1538-7445.AM2013-3950
Abstract 3953: The omental microenvironment promotes ovarian cancer metastasis and enhances CD-133 mediated self-assembly of ovarian cancer spheroids.
Authors: Brewer Molly A. , Sun Guigin , Anderson Matthew , Meng Fanliang , Zhong Mei 
Published: August 2014

Abstract
Objective: Recent evidence suggests that the human omentum functions as a niche that promotes ovarian cancer metastasis. We investigated the role of the omentum in sequestration and enhancement of ovarian cancer stem cells.
Materials and Methods: To further explore this unique phenomenon, we examined the ability of cells isolated from ovarian cancer implants at distinct anatomic sites to create multicellular aggregates known as spheroids. In ovarian and other cancers, spheroids promote a pluripotent phenotype and play a critical role in metastasis.
Results: We found that ovarian cancer cells recovered from omentum express higher levels of the pluripotency-associated antigen CD133 and create larger numbers of more rapidly growing spheroids than cells recovered from the tubo-ovarian complex. Although CD133+ or CD44+ ovarian cancer cells are equally capable of creating large spheroids, spheroids self-assembled from CD133+ ovarian cancer cells are significantly more tumorigenic in vivo than CD44+, CD133−CD44− or unsorted cells. We also found that spheroids self-assembled from CD133+ ovarian cancer cells migrate to both the ovary and omentum of SCID mice and that CD133+ ovarian cancer cells induce intraperitoneal xenografts when inoculated subcutaneously. In contrast, our data indicate that spheroids self-assembled from CD44+ cells preferentially induce tumor adjacent to their inoculation site. Targeting CD133 expression inhibits the in vivo tumorigencity of spheroids assembled from A2780 ovarian cancer cells.
Conclusions: In addition to delineating novel pathways by which the omental microenvironment promotes ovarian cancer metastasis, these findings establish a new paradigm for understanding how ovarian cancer stem cells can be potentially maintained or regenerated within the peritoneal cavity. Strategies to target the omental niche have enormous potential to improve ovarian cancer outcomes.
Citation Format: Molly A. Brewer, Guigin Sun, Matthew Anderson, Fanliang Meng, Mei Zhong. The omental microenvironment promotes ovarian cancer metastasis and enhances CD-133 mediated self-assembly of ovarian cancer spheroids. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3953. doi:10.1158/1538-7445.AM2013-3953
Abstract 3960: Whole body irradiation extends the duration of antitumor immunity toward established prostate tumors by adoptively transferred CD8+ T cells in TRAMP mice.
Authors: Ward-Kavanagh Lindsay , Cooper Timothy , Schell Todd D. 
Published: August 2014

Abstract
Adoptive T cell transfer following whole body irradiation (WBI) can induce dramatic tumor regression in a subset of metastatic melanoma patients. We previously found that this approach also eliminates established autochthonous SV40 T-antigen induced murine brain tumors. However, the broader utility of this immunotherapy approach has not been systematically evaluated in solid tumors of different tissue origin. Here, we assessed the efficacy of applying WBI with adoptive T cell transfer to an SV40 T-antigen driven murine model of prostate cancer (TRAMP) previously shown to rapidly tolerize tumor-specific CD8+ T cells. TRAMP mice bearing established prostate tumors were treated with 475cGy WBI followed by adoptive transfer of T-antigen-specific T cell receptor transgenic CD8+ T cells. Accumulation, phenotype and function of the transferred T cells were monitored by flow cytometry, while therapeutic impact on mouse prostate tumors was assessed by histological scoring. Transferred T cells proliferated in both irradiated and non-irradiated TRAMP mice, but accumulated to significantly higher levels and persisted longer in the secondary lymphoid organs and prostate of irradiated mice. WBI also significantly increased the proportion of T cells that produced the effector molecule granzyme B. Prostate-infiltrating T cells in both treatment groups exhibited an effector differentiated phenotype, although neither developed a significant population of IFNγ-producing cells. Gross observations revealed that the urogenital tract in irradiated TRAMP mice was significantly smaller than that of non-irradiated mice two weeks after transfer, corresponding with a modest but statistically significant drop in pathological score. By three weeks after transfer, when prostate-infiltrating T cells had dramatically contracted in irradiated TRAMP mice, cumulative histological scores were generally equivalent although only mice in the non-irradiated treatment group had progressed to adenocarcinoma. Our results suggest that the addition of irradiation extends the persistence of functional tumor-specific T cells in the highly tolerogenic microenvironment of the TRAMP prostate. T cell accumulation was associated with a short-term delay in progression of established tumors.
Citation Format: Lindsay Ward-Kavanagh, Timothy Cooper, Todd D. Schell. Whole body irradiation extends the duration of antitumor immunity toward established prostate tumors by adoptively transferred CD8+ T cells in TRAMP mice. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3960. doi:10.1158/1538-7445.AM2013-3960
Abstract 3967: ErbB2/HER2-specific natural killer cells for adoptive immunotherapy of glioblastoma.
Authors: Zhang Concong , Schönfeld Kurt , Burger Michael , Genßler Sabrina , Sahm Christiane , Brendel Christian , Naundorf Sonja , Odendahl Marcus , Köhl Ulrike , Tonn Torsten , Grez Manuel , Steinbach Joachim P. , Wels Winfried S. 
Published: August 2014

Abstract
In addition to primary natural killer (NK) cells, continuously growing cytotoxic cell lines such as NK-92 are being considered for adoptive cancer immunotherapy. High cytotoxicity of NK-92 has been shown against malignant cells of hematologic origin in preclinical studies, and general safety of infusion of NK-92 cells has been established in phase I clinical trials. To enhance their therapeutic utility, we genetically modified NK-92 cells to express chimeric antigen receptors (CAR) specific for different tumor-associated surface antigens including ErbB2 (HER2). Such CAR were composed of a tumor-specific scFv antibody fragment fused via hinge and transmembrane domains to intracellular signaling proteins such as CD3 zeta chain or a composite CD28-CD3 zeta fusion molecule.
Glioblastoma multiforme (GBM) is the most common and severe intracranial malignant tumor in humans. Despite aggressive therapy, recurrence of GBM is very frequent, and the median survival of GBM patients is only 12 to 15 months. Since enhanced ErbB2 expression was found in up to 80% of GBM cases, adoptive ErbB2-targeted immunotherapy may represent a more efficient alternative to standard therapy. For development towards clinical applications, here we generated a lentiviral second generation CAR construct (5.28.z) specific for the ErbB2 antigen, and established GMP-compliant protocols for transduction and expansion of NK-92 cells. An ErbB2-specific single cell clone (NK-92/5.28.z) was isolated, which showed high and selective cytotoxicity towards different established ErbB2-expressing glioblastoma cells and tumor cells of various other origins in vitro, as well as specific tumor homing in murine in vivo models. Treatment with NK-92/5.28.z cells also resulted in marked inhibition of the growth of subcutaneous glioblastoma xenografts in NOD/SCID γc KO mice. Ongoing work now focuses on evaluating the feasibility and efficacy of intracranial application of NK-92/5.28.z cells in orthotopic xenograft models of ErbB2-positive glioblastoma cells as a basis for further development of these cells as an adoptive immunotherapy for glioblastoma patients.
Citation Format: Concong Zhang, Kurt Schönfeld, Michael Burger, Sabrina Genßler, Christiane Sahm, Christian Brendel, Sonja Naundorf, Marcus Odendahl, Ulrike Köhl, Torsten Tonn, Manuel Grez, Joachim P. Steinbach, Winfried S. Wels. ErbB2/HER2-specific natural killer cells for adoptive immunotherapy of glioblastoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3967. doi:10.1158/1538-7445.AM2013-3967
Abstract 3975: Regression of established tumors requires timely adoptive T cell transfer following whole body irradiation.
Authors: Cozza Eugene M. , Budgeon Lynn R. , Christensen Neil D. , Schell Todd D. 
Published: August 2014

Abstract
Adoptive immunotherapy with CD8+ T cells has achieved some success in treating established cancer. Response rates are increased by preconditioning the patient with lymphodepleting whole body irradiation (WBI) prior to T cell transfer, including an increased fraction of complete responses. Using a mouse model of autochthonous brain cancer, we previously demonstrated that adoptive transfer of tumor-specific T cells following WBI promotes complete regression of established tumors and long-term survival. However, the mechanisms required to achieve complete responses remain to be defined. Here we investigate kinetic requirements for adoptive T cell transfer to achieve tumor control following WBI. To test the hypothesis that adoptive transfer early after irradiation is required for maximum long-term tumor control, we delayed adoptive transfer of T cells to tumor-bearing mice at varying intervals following irradiation. We show that delay of adoptive transfer did not affect initial T cell priming or the timing of initial appearance of activated T cells at the tumor site. However, we observed a modest decrease in T cell accumulation at the earliest appearance of cells in the brain (5 days post-transfer). Tumors were completely eliminated within 10 days in mice that received T cell transfer one day following WBI, while delayed transfer abrogated this effect. When adoptive transfer was delayed by one week following WBI, incomplete tumor regression was observed at 10 days post-transfer. Although mice in this group lived significantly longer than control animals, they eventually succumbed to lethal tumor recurrence. Our data suggest that lymphodepleting doses of WBI promote a prolonged window for effective T cell priming against the endogenous tumor antigen, but that optimal therapeutic potential requires T cell transfer early after irradiation conditioning. Supported by research grant CA02500 from the National Cancer Institute/National Institutes of Health.
Citation Format: Eugene M. Cozza, Lynn R. Budgeon, Neil D. Christensen, Todd D. Schell. Regression of established tumors requires timely adoptive T cell transfer following whole body irradiation. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3975. doi:10.1158/1538-7445.AM2013-3975