tbuckley/cabot-search huggingface dataset:
Abstract LB-244: Implication of secretory mucin MUC5AC and its glycan modification for detection of pancreatic cancer
Authors: Chihiro Hayashi, Joseph Carmicheal, Alexey Krasnoslobodtsev, Ying Haung, Randall E. Brand, Surinder K. Batra, Sukhwinder Kaur
Journal: Cancer Research (2017)

Abstract Background and Aims Pancreatic Cancer (PC) is often discovered in late stages, which contributes to its extreme lethality. Early detection is key to improved curative response and increased survival. This study explored the potential of secretory mucin MUC5AC and its glycosylation (Sialyl-Lewis A and Disialyl-Lewis A) states in combination with carbohydrate antigen CA19.9 for early diagnosis of PC. Methods Sandwich ELISA and radioimmunoassay were utilized to measure patient serum for levels of MUC5AC and CA19.9, respectively. A blinded reference set was obtained from the NCI’s Early Detection Research Network Program (n=242): healthy control (HC, N=50), chronic pancreatitis (CP, N=59), acute biliary obstruction (ABO, N= 30), stage IA/IB/IIA (N=52), and stage IIB PC (N=41), to assess the diagnostic performance of MUC5AC. Further, glycans on MUC5AC (Disialyl Lewis A, Lewis A, Blood group H (BGH) antigen) were measured via Surface Enhanced Raman Spectroscopy (SERS). Results MUC5AC levels were significantly increased in patients with stage IA/IB/IIA/IIB PC in comparison to HC, ABO and CP. MUC5AC efficiently differentiated stage IA/IB/IIA PC from healthy controls [AUC- 0.707], ABO [AUC- 0.662], and CP [AUC- 0.745]. CA19.9 differentiated stage IA/IB/IIA PC from healthy controls [AUC- 0.727], ABO [AUC-0.537] and CP [AUC- 0.675]. The MUC5AC combination with CA19.9 significantly improved the performance of CA19.9 alone: healthy controls [AUC- 0.761], ABO [AUC-0 .679], and CP [AUC- 0.753]. Further, PC serum was shown to express MUC5AC with greater Sialyl-Lewis A glycosylation in comparison to Disialyl-Lewis A glycosylation. Further, the reverse trend for these glycosylation was observed in CP and BC group. Conclusions MUC5AC is an early-stage PC biomarker that offers improved performance with CA19.9 for the detection of PC. Also, measurement of MUC5AC glycan modification will aid in the better differentiation of PC from healthy controls and high risk groups (CP, ABO). Further, the ratio of disialyl to CA19.9 glycosylation of MUC5AC is a novel way to differentiate between PC and benign conditions. Citation Format: Chihiro Hayashi, Joseph Carmicheal, Alexey Krasnoslobodtsev, Ying Haung, Randall E. Brand,, Surinder K. Batra, Sukhwinder Kaur. Implication of secretory mucin MUC5AC and its glycan modification for detection of pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-244. doi:10.1158/1538-7445.AM2017-LB-244
Abstract 5043: Population pharmacokinetic model for OT-101 - A TGF-β2-specific antisense oligonucleotide in cancer patients
Authors: Wen Wang, Kevin Ng, David Nam, Vuong Trieu, Larn Hwang
Journal: Cancer Research (2017)

Abstract Background: OT-101 (Trabedersen) is a phosphorothioate antisense oligodeoxynucleotide specifically inhibiting the expression of transforming growth factor-beta 2 (TGF-β2), whose overexpression is a pivotal factor for malignant progression in solid tumors. In the clinical Phase I/II study, plasma pharmacokinetic (PK) profile of OT-101 administered intravenously was evaluated in patients with advanced tumors. A population PK model was built to further understand the factors contributing to the variability in PK of OT-101. Methods: A total of 61 patients with pancreatic cancer (n=37), malignant melanoma (n=19), or colorectal carcinoma (n=5) were treated with OT-101 with escalating doses in 2 treatment schedules (1st schedule: 7-days on, 7-days off; 2nd schedule: 4-days on, 10-days off; up to 10 cycles). The PK analysis was only performed on Cycle 1 and, when applicable, Cycle 2. Blood samples were collected from patients at planned time points from before start of infusion to 7 days (1st schedule) or 10 days (2nd schedule) after stop of infusion. The plasma concentration data of OT-101 were used to build a population PK model using Phoenix NLME software. The influence of age, gender, body mass index (BMI), body weight (BW), height, cancer type, and treatment schedule as covariates on PK was evaluated. Results: With exclusion of protocol deviations, a total of 1444 plasma sample concentration data from 100 patient cycles were examined. The concentration time course of OT-101 was best described by a two-compartment model. The model estimated the PK parameters as follows: total body clearance, 0.17 mL/h; distribution volume of the central compartment, 4.69 L; inter-compartmental clearance, 3.31 L/h; distribution volume of the peripheral compartment, 5046.44 L. BW was identified as a covariate on OT-101 inter-compartmental clearance, with KBW as -ve 1.48. Conclusion: The PK parameters of OT-101 were best described by a two-compartment model. OT-101 was largely distributed in the peripheral tissues. The influence of age, gender, BMI, height, cancer type and treatment schedule on the PK of OT-101 was not identified. The model will be used for a sparse population PK study during the planned phase III trial of OT-101 in pancreatic cancer. Citation Format: Wen Wang, Kevin Ng, David Nam, Vuong Trieu, Larn Hwang. Population pharmacokinetic model for OT-101 - A TGF-β2-specific antisense oligonucleotide in cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5043. doi:10.1158/1538-7445.AM2017-5043
Abstract 3733: Adenine nucleotide translocase2 mediates18F-FDG uptake in dedifferentiated thyroid cancer
Authors: Chul-Hee Lee, Hyewon Youn, Seock-Jin Chung, Ha Kim, Cho Rong Park, Mi Jeong Kim, Young Joo Park, Sun Wook Cho, Keon Wook Kang, June-Key Chung
Journal: Cancer Research (2017)

Abstract Objectives: 18F-fluorodeoxyglucose (FDG), an analogue of glucose, provides valuable functional information based on the increased glucose uptake and glycolysis in malignant tumor cells. Although both glucose transporter-1 (GLUT-1) and hexokinase2 (HK2) activity have been considered to associate with FDG uptake, the molecular mechanisms that determine FDG uptake are still largely unknown. Adenine nucleotide translocase 2 (ANT2) in the mitochondria inner membrane was reported to relate with tumor malignancy. We investigated the correlation between FDG uptake and Glut-1, HK2, and ANT2 expression in thyroid cancers throughout various spectrums of differentiation status. Methods: N-thy-ori (normal human thyroid cells), WRO (follicular cancer), BHP10-3 and TPC-1 (papillary cancer), and FRO (anaplastic cancer) were used for this research. GLUT-1, HK2, and ANT2 expressions were measured by western blot. ANT2 siRNAs and pcDNA3.1-ANT2 vectors were used to modify ANT2 expression. FDG uptakes were measured in thyroid cells and human embryonic kidney cells (293FT) with HK2 or ANT2 transfection. For patient tissue analysis, 95 thyroid tissue-array cores were evaluated, and which are classified 36 as normal, 44 as poorly differentiated (PD), and 15 as anaplastic thyroid cancer (ATC). ANT2 expression was measured by immunostaining, scored from 1 to 5. Results: FDG uptake in thyroid cancer cells was increased in anaplastic and poorly differentiated cells (P&amp;lt;0.001). GLUT-1 expression was higher in both TPC-1 and FRO than other cells. Whereas, HK2 was expressed only in cancer cells. ANT2 was expressed only in FRO cells and the highest FDG accumulation was also observed in FRO. ANT2 siRNA showed decreased FDG uptake (0.55-fold) and ANT2 overexpression increased FDG uptake (1.7-fold). In 293FT cells, HK2 and ANT2 transfection increased FDG uptake (P&amp;lt;0.01). PD tissues (mean = 41.7, SD = 19.7) and ATC (mean = 48.0, SD = 25.6) tissues from patients showed higher ANT2 expression than normal (P&amp;lt;0.05). Conclusion: We showed that ANT2 was expressed only in anaplastic thyroid cancer cells, and this was related to FDG uptake. Higher level of ANT2 expression was observed in dedifferentiated cancer, and this indicates that ANT2 can be used as a marker of malignancy in thyroid cancer. Citation Format: Chul-Hee Lee, Hyewon Youn, Seock-Jin Chung, Ha Kim, Cho Rong Park, Mi Jeong Kim, Young Joo Park, Sun Wook Cho, Keon Wook Kang, June-Key Chung. Adenine nucleotide translocase2 mediates 18F-FDG uptake in dedifferentiated thyroid cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3733. doi:10.1158/1538-7445.AM2017-3733
Abstract 2384: Aberrant expression of PDZ binding kinase modulates human pancreatic cancer cell invasion
Authors: Charles Hinzman, Jose Trevino, Partha P. Banerjee
Journal: Cancer Research (2017)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related deaths and projected to be the second leading cause of cancer deaths by 2030. Incidence to mortality ratio for PDAC is almost one suggesting its aggressive phenotype. The poor survival rate of PDAC patients is due to metastasis to distant organs, and therefore, recent focus has been aimed towards the identification of molecular targets that drives metastatic disease. We are investigating an under-studied kinase, PDZ-domain binding kinase (PBK) as a target for pancreatic cancer (PanCa) therapy. PBK is a dual-specificity serine/threonine kinase involved in mitosis and invasive behavior of cancer cells. It is expressed physiologically in testis, but aberrant expression results in an aggressive phenotype in a variety of cancers. Our results demonstrate that PBK expression varies across a panel of human PanCa cell lines, and directly correlates with their invasive ability. Similarly, a panel of patient-derived primary PanCa shows higher PBK levels associated with aggressive behavior and invasion. To assure specificity of PBK to this invasive phenotype, we measured the effect of PBK overexpression or knockdown on the PanCa lines’ invasive ability. Overexpression of PBK in low PBK expressing cells increased PanCa invasion ~10-fold, while PBK knockdown reduced invasive ability ~5-fold. Immunohistochemical analyses of resected human PanCa specimens revealed that PBK is present in the majority of human PanCa tissue samples tested but not in the adjacent normal pancreatic tissue. Interestingly, aberrant PBK localization was found in even early stages of PanCa development and was sustained throughout its progression. In search of molecular effectors of invasion regulated by the PBK, we examined various genes/proteins that are involved in cancer cell invasion and metastasis. RelB a well-known metastatic inducer in various cancers was found to be a major payer in PanCa and regulated by PBK. These data indicate a novel molecular pathway of PBK where its presence plays a role in invasion of human PanCa cells. Therefore, the role of PBK in promoting cancer cell invasion, combined with its general lack of expression in normal cells, nominates PBK as a potentially important therapeutic target for pancreatic cancer. Citation Format: Charles Hinzman, Jose Trevino, Partha P. Banerjee. Aberrant expression of PDZ binding kinase modulates human pancreatic cancer cell invasion [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2384. doi:10.1158/1538-7445.AM2017-2384
Abstract 3747: msa2 biotin-binding CAR combined with biotinylated tumor-specific antibodies or DNA aptamers for universal cancer immunotherapy
Authors: Jason J. Lohmueller, James D. Ham, Olivera J. Finn
Journal: Cancer Research (2017)

Abstract Chimeric antigen receptor T cells (CAR-Ts) are highly promising as cancer therapeutics, but the creation of CARs for new antigens remains a laborious process. As an alternative strategy researchers are designing universal “tag-CARs” that instead of directly recognizing tumor antigens, recognize tags on tumor-specific antibodies bound to tumor cells, thereby activating T cell effector functions. Here we report the creation of a novel tag-CAR that uses the high affinity monomeric streptavidin 2 (msa2) biotin binding domain to target cancer cells labeled with biotinylated tumor-specific antibodies or DNA aptamers. We constructed lentiviral vectors encoding msa2 CARs with three different signaling architectures - CD28-zeta, CD28-OX40-zeta, and 4-1BB-zeta. After confirming that each msa2 CAR was efficiently expressed on the surface of Jurkat and primary human T cells, we found that plate-immobilized biotin was capable of specifically inducing T cell activation markers and cytokine production. We then stained a variety of cancer cell lines with various tumor-specific biotinylated antibodies or DNA aptamers targeting tumor antigens such as MUC1, CD19, CD20, and EGFR and found that the stained cells specifically activated the msa2-CAR cells and led to cytokine production. We are currently investigating the ability of msa2-CAR cells to lyse antibody and aptamer-bound cancer cells and will be assessing their ability to shrink tumors in a human tumor xenograft mouse model. Citation Format: Jason J. Lohmueller, James D. Ham, Olivera J. Finn. msa2 biotin-binding CAR combined with biotinylated tumor-specific antibodies or DNA aptamers for universal cancer immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3747. doi:10.1158/1538-7445.AM2017-3747
Abstract LB-267: Metabolic alterations in tumors cause cachexia in pancreatic cancer
Authors: Aneesha Dasgupta, Surendra K. Shukla, Venugopal Gunda, Nina V. Chaika, Pankaj K. Singh
Journal: Cancer Research (2017)

Abstract Cancer-associated cachexia is a complex metabolic syndrome which leads to excessive loss of skeletal muscle and adipose deposits. Up to 80% of pancreatic cancer patients suffer from cachexia and nearly one third die due to complexities related to the syndrome. Treatment of cachexia will not only improve the standard of living of pancreatic cancer patients but would also improve the patient survival. In the clinic, the majority of cancer patients are diagnosed at the refractory phase of cachexia, which cannot be reversed by dietary interventions. Till late, cachexia has mainly been attributed to systemic inflammation caused by cytokines released from the host and the tumor. But anti-inflammatory therapies have not shown promising results in clinical trials. Hence, there is an urgent need to identify new targets to combat cancer cachexia. It has been previously shown that there are constant metabolic interactions between the host body and the tumor. Increase in tumor burden and its demand for nutrition forces the host body to reprogram its metabolism leading to the breakdown of host body proteins into amino acids, which gets taken up and converted into carbohydrates by the tumor. To study the role of metabolic pathways in tumor cells on cachectic factor secretion, we pre-treated pancreatic cancer cells with metabolic inhibitors 3-Bromopyruvic acid and bis-2-(5-phenylacetomido-1, 2, 4-thiadiazol-2-yl) ethyl sulfide (BPTES). The conditioned media from control and treated cells were then evaluated for myotube degeneration potential in C2C12-dfferentitaed myotubes by measuring myotube thickness, protein content and expression of muscle specific ubiquitin ligases. We observed that that pre-treated conditioned-media had reduced myotubes degenerating potential as compared to controls. Furthermore, we inhibition of glycolytic flux in tumor cells by treatment with ketone bodies also diminished myotubes degenerating potential. Tumor-bearing mice had decreased tumor growth and cachexia when fed on a ketogenic diet. In conclusion, metabolic reprograming of tumor cells plays an important role in inducing pancreatic cancer-induced cachexia and delineating the metabolic pathways is crucial to elucidate important therapeutic targets for cancer cachexia. Citation Format: Aneesha Dasgupta, Surendra K. Shukla, Venugopal Gunda, Nina V. Chaika, Pankaj K. Singh. Metabolic alterations in tumors cause cachexia in pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-267. doi:10.1158/1538-7445.AM2017-LB-267
The Benefit of Early Preventive Dental Care for Children
Authors: Joe K. Gerald
Journal: JAMA Pediatrics (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Abstract 16: Evaluation of the efficacy of clotrimazole treatment in human melanoma cell lines that overexpress the multidrug resistance-associated protein (MRP) and the lung resistance-related protein (LRP)
Authors: Steven D. Blake, Shelby G. McKamey, Christopher M. Tweed, David W. Koh
Journal: Cancer Research (2017)

Abstract Drug resistance to chemotherapy, mediated in part by overexpression of P-glycoprotein (MDR-1), multidrug resistance-associated protein (MRP), or lung resistance-realted protein (LRP), continues to be a major problem in the treatment of melanoma. Because we previously demonstrated the ability of clotrimazole to enhance cytotoxicity in human metastatic melanoma cells, here we evaluated the ability of clotrimazole to treat drug-resistant human melanoma cells that overexpress MRP and/or LRP. We utilized human melanoma cell lines that overexpress either MDR or LRP, and human melanoma cell lines that overexpress both. Cell growth and cell death were analyzed by flow cytometry, proliferation assays, and immunoblotting after drug treatments and RNA interference. Clotrimazole caused significant decreases in proliferation and increases in cell death in both drug-sensitive melanoma lines and those overexpressing MRP and LRP. No extensive cell death was induced by clotrimazole treatment in noncancerous human skin cell lines. These results indicate that clotrimazole selectively induces cytotoxicity in both drug-sensitive and drug-resistant melanoma lines. As clotrimazole is known to inhibit various transient receptor potential (TRP) ion channels, we pretreated these melanoma lines with TRP inhibitors or RNAi. Inhibitors of the TRP melastatin-8 channel (TRPM8) or TRP vanilloid-1 (TRPV1) failed to produce comparable levels of cell death caused by clotrimazole. However, RNAi silencing of the TRPM2 cation channel caused significant levels of cell death in both drug-sensitive and drug-resistant melanoma lines. These results indicated that inhibition of TRPM2 channels may have a primary role in the ability of clotrimazole to treat drug-sensitive and drug-resistant melanoma lines. In conclusion, this study demonstrated that clotrimazole selectively increases cell death in drug-resistant melanoma lines, with minimal deleterious effects in normal skin cells. Taken together, we conclude that clotrimazole has in vitro efficacy toward the treatment of drug-resistant human melanoma cells. Thus, these preliminary studies indicate that clotrimazole has the potential to successfully treat drug resistant melanoma in the future. Citation Format: Steven D. Blake, Shelby G. McKamey, Christopher M. Tweed, David W. Koh. Evaluation of the efficacy of clotrimazole treatment in human melanoma cell lines that overexpress the multidrug resistance-associated protein (MRP) and the lung resistance-related protein (LRP) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 16. doi:10.1158/1538-7445.AM2017-16
Alcohol versus dry umbilical cord care among newborn infants in occupied Palestinian territory: a controlled trial
Authors: Maher Shahrour, Nour AlHuda Sawalha, Murad Masri, Hanan Rajabi, Mohammad Salah Eddin, Taha Jo'beh, Sundus Shalabi, Ala' Lafi, Ebtihal Jawabra, Waseem Khreim, Sa'eed Natsheh, Motee Abu Awwad, Hatem Khammash
Journal: The Lancet (2017)
Abstract 56: Antibody-drug conjugates containing glucuronide-tubulysin payloads display activity in MDR+ and heterogeneous tumor models
Authors: Patrick J. Burke, Joseph Z. Hamilton, Joshua H. Hunter, Julia H. Cochran, Thomas A. Pires, Christopher I. Leiske, Kim K. Emmerton, Peter D. Senter, Robert P. Lyon, Scott C. Jeffrey
Journal: Cancer Research (2017)

Abstract While antibody-drug conjugates (ADCs) find increasing application in cancer treatment regimens, de novo or treatment-emergent resistance mechanisms could impair clinical benefit. Two resistance mechanisms that emerge under continuous ADC exposure in vitro include upregulation of transporters that confer multidrug resistance (MDR+) and loss of cognate antigen expression. New technologies that circumvent these resistance mechanisms may serve to extend the utility of next generation ADCs. Recently, we developed the quaternary ammonium linker system to expand the scope of conjugatable payloads to include tertiary amine-containing compounds and applied the linker to tubulysins, a highly potent class of microtubule disrupting agents that maintain activity in MDR+ cell lines. Quaternary ammonium-linked glucuronide-tubulysin drug-linkers were synthesized and evaluated as ADCs. The resulting conjugates were potent and immunologically specific across a panel of cancer cell lines, including those displaying the MDR phenotype. The ADCs also demonstrate potent bystander activity in a co-culture model containing a mixture of antigen-positive and -negative cell lines. Incorporation of a PEG12 side chain in the linker enabled loading at 8-drugs/Ab for increased in vivo potency while maintaining suitable ADC pharmacokinetic properties. In vivo, the glucuronide-tubulysin conjugates displayed activity in MDR+ xenograft models and bystander activity in an admixed Ag+/Ag- heterogeneous tumor model. Thus, the glucuronide-tubulysin drug-linkers represent a promising new payload for ADCs, combining conjugate potency in the presence of the MDR phenotype with robust activity in models of tumor antigen heterogeneity. Citation Format: Patrick J. Burke, Joseph Z. Hamilton, Joshua H. Hunter, Julia H. Cochran, Thomas A. Pires, Christopher I. Leiske, Kim K. Emmerton, Peter D. Senter, Robert P. Lyon, Scott C. Jeffrey. Antibody-drug conjugates containing glucuronide-tubulysin payloads display activity in MDR+ and heterogeneous tumor models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 56. doi:10.1158/1538-7445.AM2017-56