tbuckley/cabot-search huggingface dataset:
PTU-012 A novel submucosal injection solution: data on safety and efficacy from a large prospective EMR series
Authors: G R Longcroft-Wheaton, R Mead, P Bhandari
Journal: Gut (2010)

<h3>Introduction</h3> Submucosal injection is an integral part of EMR. The ideal solution will produce a long lasting high elevation, and an avascular field with delineation of tissue planes. This requires a combination of various drugs and solutions. However, no such mix is commercially available. This has resulted in a wide range of mix being used in this country, with no data on the safety, efficacy and long-term results of these solutions. We have developed an ideal mix of gelofusine (colloid) to provide a long lasting lift with adrenaline to reduce the vascularity of the field and indigo carmine to adequately delineate tissue planes. We aim to illustrate the feasibility, safety and efficacy and long-term effects of our novel submucosal lifting solution. <h3>Methods</h3> The lifting solution was: 500 mls gelofusine, 2 mls 1:1000 adrenaline and 5 mls indigocarmine 0.4%. We reviewed all EMRs since 2005. Records were assessed to collect data on efficacy of the solution, immediate and late mucosal and systemic effects. Data were collected on type and size of lesions, procedure time and volume of solution used. <h3>Results</h3> A total of 546 lesions were removed. 411 polypectomies and 135 upper GI EMRs. Volume used was between 5-250 mls, dependent on lesion size and procedure time (range 20 min–180 min). Distribution of upper GI lesions: 99 oesophageal EMRs, 20 gastric EMRs and 16 duodenal EMRs. Endoscopic follow-up data were available on 107 cases, with a mean interval of 3 months (range: 2–6 months). There was no evidence of immediate or late complications, including tissue injury, necrosis or stenosis related to the solution. For the lower GI lesions: 411 polyps removed. There were 143 polyps &gt;2 cm in size. Left sided lesions=121 (median 45 mm range 20–150), right sided lesions=22 (median 31 mm, range 20–50). Procedure time 20 min–180 min. There were follow-up data on 117 colonic EMRs, with a mean interval of 4 months (range 0.5–60 months). There was no evidence of any late complications, including tissue injury necrosis or stenosis at the previous polypectomy sites. The endoscopist found the solution extremely effective and provided good lift after one injection in all of the cases examined. There was a short lived 5–20% rise in pulse rate. There were no immediate cardiac complications preventing completion of the procedures. No anaphylaxis or allergic reaction. There was no local or systemic sepsis related to the solution. No obvious renal or hepatic effects reported. <h3>Conclusion</h3> Largest reported series on submucosal injection solution in the world; Have clearly demonstrated the feasibility and efficacy of this novel injection mix; Shows immediate and long-term safety of this solution; Shows some systemic effects like tachycardia so caution is advised in cardiac patients.
The role of bevacizumab in combination with pegylated liposomal doxorubicin in patients with platinum-resistant recurrent or refractory ovarian cancers.
Authors: H. Kouta, K. Kudoh, M. Takano, R. Kikuchi, T. Kita, T. Goto, K. Furuya, Y. Kikuchi
Journal: Journal of Clinical Oncology (2011)

5018 Background: Currently, pegylated liposomal doxprubicin (D) is used as one of the standard treatment options in recurrent or refractory ovarian cancer. Vascular endothelial growth factor (VEGF) plays a central role in tumor angiogenesis and is regarded as a promising therapeutic target against ovarian cancers. Thus, we attempted to determine therapeutic effects of bevacizumab (B) on D in heavily pretreated patients with recurrent and progressed ovarian cancer. Methods: Thirty-eight patients with platinum-resistant recurrent or refractory ovarian cancers received at least more than 3 cycles of weekly B-D consisting of B: 2mg/kg and D: 10mg/m2 (3 weeks, one week rest). The primary end point was response according to response evaluation criteria in solid tumor (RECIST) or CA125 GCIG criteria. Results: In 24 RECIST-assessable cases, 2 (8%) had complete remission (CR) and 9 (38%) had partial remission (PR), resulting in response rate of 46%. Clinical benefit rate (CR+PR+SD) was 75%. Of 30 patients evaluable for CA125 response, 13 (43%) had a response (decrease of >50%), and 11 (37%) patients had not progressed (within doubling of CA125) following 6 months on treatment. Median progression-free survival (PFS) was 8 months. Any hematological adverse effect was not observed in the present study. Gastrointestinal perforation was observed in one case and was conservatively treatable. Although nasal bleeding was frequently observed, no treatment was required. An induced hypertension was also observed and manageable. Hand-foot syndrome was seen in 6 (16%) of 38 patients and treatment was required in three cases. Of note, Six (75%) of 8 cases with that did not respond to previous monthly D (50mg/m2) showed response to following weekly B-D. Conclusions: B seemed to enhance effect of D in platinum-resistant recurrent or refractory ovarian cancer patients. Weekly B-D warrants further clinical study in such clinical settings.
Data Visualization of Multiparameter Information in Acute Lymphoblastic Leukemia Expands the Ability To Explore Prognostic Factors.
Authors: Susanne Ragg, Marc B. Rosenman, Eve M. Doucette, Zhong Yan, Julie C. Haydon, Jada H. Paine, Nadine D. Lee, Terry Vik, Ketan Mane, Katy Borner
Journal: Blood (2005)
Abstract 3587: Developing targeted therapy for the treatment of drug-resistant ovarian cancer
Authors: Kelly M. Kreitzburg, Zacchary Dobbins, Ashwini Katre, Tooba Anwer, Ronald Alvarez, Charles N. Landen, Karina J. Yoon
Journal: Cancer Research (2015)

Abstract Despite therapeutic approaches that combine surgical cytoreduction with chemotherapy, ovarian cancer remains the principal cause of death among women with gynecological malignancies. Virtually all patients relapse with drug-resistant disease. To elucidate the biological mechanisms that contribute to this resistance, we established a repository of patient-derived xenograft (PDX) models of ovarian cancer in mice. We used RNA-seq and Ingenuity Canonical Pathway software to analyze chemotherapy induced changes in expression patterns of six of these models. We found that the sphingosine-1-phosphate (S1P) signaling pathway is one of the pathways most affected by paclitaxel and cisplatin treatment, with altered expression in seven genes associated with the S1P pathway (p&amp;lt;0.05). The biologically active lipid S1P contributes to cell growth, survival/apoptosis, angiogenesis, migration and metastasis in normal and tumor tissue. The S1P pathway has also been reported to be involved in chemoresistance in several types of solid tumors. The S1P pathway depends predominately on three core lipids: ceramide, sphingosine, and S1P. These molecules are termed the ceramide-sphingosine-S1P rheostat, and their expression is tightly regulated both intra- and extra-cellularly. Recent studies suggest a correlation between aberrations in the S1P pathway and poor prognosis, advanced stage, and resistance to chemotherapy and radiation. Preliminary data using the sphingosine analog FTY-720 is consistent with the hypothesis that the S1P pathway regulates cell survival by effecting changes in the relative levels of ceramide, sphingosine, and S1P, as a cytoprotective autophagic mechanism to evade chemotherapy-induced cytotoxic effects. Cell proliferation assays, immunoblots, and fluorescence microscopy results of ovarian cancer cells exposed to FTY-720 in combination with carboplatin or paclitaxel treatment provide evidence that the S1P pathway may evade cell death through the induction of cytoprotective autophagy. Our data suggest that the S1P pathway contributes to the chemoresistance of ovarian cancer cells to conventional chemotherapeutic agents. Citation Format: Kelly M. Kreitzburg, Zacchary Dobbins, Ashwini Katre, Tooba Anwer, Ronald Alvarez, Charles N. Landen, Karina J. Yoon. Developing targeted therapy for the treatment of drug-resistant ovarian cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3587. doi:10.1158/1538-7445.AM2015-3587
PTU-003 Extracorporeal shock wave lithotripsy with a transportable mini-lithotripter and subsequent endoscopic duct clearance for treatment of obstructive pancreatic duct stones
Authors: V Milovic, T Wehrmann, C F Dietrich, A Bailey, B Braden
Journal: Gut (2010)

<h3>Abstract</h3> The neural substrates for processing classical rewards such as food or drugs of abuse are well-understood. In contrast, the mechanisms by which organisms perceive social contact as rewarding and subsequently modify their interactions are unclear. Here we tracked the gradual emergence of a repetitive and highly-stereotyped parental behavior and show that trial-by-trial performance correlates with the history of midbrain dopamine (DA) neuron activity. We used a novel behavior paradigm to manipulate the subject’s expectation of imminent pup contact and show that DA signals conform to reward prediction error, a fundamental component of reinforcement learning (RL). Finally, closed-loop optogenetic inactivation of DA neurons at the onset of pup contact dramatically slowed emergence of parental care. We conclude that this prosocial behavior is shaped by an RL mechanism in which social contact itself is the primary reward. <h3>One-Sentence Summary</h3> Maternal interactions with offspring are shaped by a dopaminergic reinforcement learning mechanism.
The Overexpression of Spliced Oncogenic Ikaros Isoforms in Philadelphia-Positive (Ph+) Acute Lymphoblastic Leukemia (ALL) Patients Is a New Mechanism of Resistance to Tyrosine Kinase Inhibitors.
Authors: I. Iacobucci, A. Lonelti, E. Ottaviani, D. Cilloni, F. Messa, S. Paolini, C. Papayannidis, G. Panagiota, S. Soverini, M. Amabile, A. Poerio, M. Rondoni, G. Saglio, F. Pane, G. Berton, A. Baruzzi, A. Vitale, R. Foà, M. Baccarani, Giovanni Martinelli
Journal: Blood (2007)
Abstract 1717: Selective induction of breast adenocarcinoma cell death via inhibition of the transient receptor potential melastatin-2 (TRPM2) cation channel
Authors: David W. Koh, Daniel P. Powell, Steven D. Blake, Joy L. Hoffman, Xiaoxing Feng
Journal: Cancer Research (2015)

Abstract Transient receptor potential melastatin-2 (TRPM2) is a plasma membrane cation channel with important physiologic roles in noncancerous cells. However, in MCF-7 and MDA-MB-231 human breast adenocarcinoma cells, we previously demonstrated that TRPM2 was present in the nucleus, and pharmacologic inhibition or RNAi silencing of TRPM2 led to decreased proliferation. In this study, we evaluated the ability of TRPM2 inhibition to produce cell death in normal breast epithelial cells and breast adenocarcinoma cells. Further, we analyzed the cell death pathways induced. Treatment with the DNA alkylating agent, N-methyl-N’-nitro-N-nitrosoguanidine (MNNG), or doxorubicin (Dox) led to increased levels of cell death in MDA-MB-231 breast adenocarcinoma cells pretreated with TRPM2 inhibitors, but not in noncancerous mammary epithelial cells after pretreatment. Similar increases in cell death were observed after RNAi silencing of TRPM2 in both MDA-MB-231 and MCF-7 breast adenocarcinoma cells after Dox or tamoxifen treatment, respectively. Investigation of apoptosis after TRPM2 inhibition demonstrated decreased levels of caspase activity and no significant effect of Q-VD-OPh, a pan-caspase inhibitor, on cell death induced by TRPM2 inhibition. Further, pretreatment with 3-methyl adenine, an inhibitor of autophagy, also produced no significant effect on cell death induced by TRPM2 inhibition. These studies indicate that apoptosis or autophagy are not the primary cell death pathways induced by TRPM2 inhibition in breast cancer cells. Also, RNAi silencing of poly(ADP-ribose) glycohydrolase (PARG) and apoptosis-inducing factor (AIF), two proteins involved in initiating or facilitating alternative pathways of cell death, produced minimal changes in cell death induced by TRPM2 inhibition. Taken together, this study demonstrated that TRPM2 inhibition selectively increases cell death in breast adenocarcinoma cells. Further, the data suggests that apoptosis, autophagy, and PARG/AIF-mediated cell death are not the primarily cell death pathways involved in the cytotoxicity caused by TRPM2 inhibition. The results therefore suggest that TRPM2 is a potential target in breast cancer, where its inhibition may cause the selective eradication of breast adenocarcinoma cells. Citation Format: David W. Koh, Daniel P. Powell, Steven D. Blake, Joy L. Hoffman, Xiaoxing Feng. Selective induction of breast adenocarcinoma cell death via inhibition of the transient receptor potential melastatin-2 (TRPM2) cation channel. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1717. doi:10.1158/1538-7445.AM2015-1717
Abstract 5322: Englerin-A prevents invasive phenotypes of renal cell carcinoma by reprogramming mesenchymal to epithelial transition: A key mechanism of its anticancer properties
Authors: Inamul Haque, Snigdha Banerjee, John A. Beutler, Sushanta K. Banerjee
Journal: Cancer Research (2015)

Abstract Renal cell carcinoma (RCC) is associated with a high frequency of metastasis and only few therapies substantially prolong survival. Recently, Englerin A (Eng A), a molecule of herb (Phyllanthus engleri) extracts, shows selective toxic effect on RCCs through the National Cancer Institute Drug Discovery panel using human cell lines as well as in vitro angiogenesis. Eng A has been reported to possess certain anticancer properties. However, whether Eng A could suppress RCC metastasis has not been fully elucidated. The epithelial-mesenchymal transition (EMT) is followed by invasion is a hallmark of metastasis malignancies including renal cancer. The aim of the present study was to examine the effects of Eng A in preventing the migration and invasion of RCCs (Caki-1 and 786-0), as well as to investigate whether Eng A may inhibit the molecular changes associated with EMT induced by transforming growth factor-beta1 (TGF-β1). We also aimed to see whether Eng A suppresses the cancer stem cell markers and spheroid formation. The investigation demonstrated that Eng A suppressed the migration and invasion of these cells under non-cytotoxic concentrations. Eng A inhibited molecular changes associated with TGF-β1-induced EMT by upregulating the epithelial markers and downregulating the mesenchymal markers. Eng A significantly reduced the levels of Twist protein, a master regulator of EMT. Eng A also inhibits the stem cell markers, i.e., CD44, ABCG2 and ALDH1 and spheroid formation. We also found that Eng A inhibits TGF-β1-induced angiogenesis. This study indicated that Eng A may serve as a potential candidate for the treatment of renal cancer metastasis. Citation Format: Inamul Haque, Snigdha Banerjee, John A. Beutler, Sushanta K. Banerjee. Englerin-A prevents invasive phenotypes of renal cell carcinoma by reprogramming mesenchymal to epithelial transition: A key mechanism of its anticancer properties. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5322. doi:10.1158/1538-7445.AM2015-5322
Abstract LB-071: Kub5-Hera/RPRD1B controls CDK1 regulation and synthetic lethality to PARP1 inhibition
Authors: Edward A. Motea, Farjana Fattah, Ling Xiao, Luc Girard, Amy Rommel, Julio Morales, Praveen Patidar, Andrew Porter, John Minna, David Boothman
Journal: Cancer Research (2015)

Abstract Aberrant CDK1 regulation induces impulsive proliferation as well as genomic and chromosomal instability in cancer cells. However, the mechanism of how CDK1 is regulated at the transcriptional level, especially under pathological conditions (e.g. cancer), remains elusive. Here, we show that Kub5-Hera (K-H), a known transcription termination factor, plays a novel role in promoting CDK1 transcription to mediate DNA repair and cellular response to PARP1 inhibition in various cancer cell lines. At the molecular level, we demonstrate via luciferase reporter assays and mutagenesis studies that K-H binds the phospho-Serine 2-containing C-terminal domain (CTD) of RNA Pol II, which is then recruited to the cell-cycle homology region (CHR) of the CDK1 promoter to efficiently stimulate CDK1 transcription. Mechanistically, the loss of K-H concomitantly reduces CDK1 mRNA/protein expression levels, which consequently compromises homologous recombination (HR)-mediated DNA repair due to the lack of BRCA1 phosphorylation for efficient function. Intriguingly, loss of K-H stimulates PARP1 activity needed for cancer cell survival. Genetic and pharmacological ablation of PARP1 activity in BRCA-proficient cells with aberrant K-H reduction leads to synthetic lethality, which is reversed by re-expression of wild-type K-H but not the mutant with attenuated RNAPII binding. The mechanistic insights gained from this study should lay foundation toward promising new tumor biology-based targets (i.e., K-H as a novel therapeutic target) and innovative strategies to reduce normal tissue toxicity, increase tumor control, and expand the use of PARP1 inhibitors (e.g., Rucaparib) against BRCA-proficient cancers with aberrant K-H loss. Citation Format: Edward A. Motea, Farjana Fattah, Ling Xiao, Luc Girard, Amy Rommel, Julio Morales, Praveen Patidar, Andrew Porter, John Minna, David Boothman. Kub5-Hera/RPRD1B controls CDK1 regulation and synthetic lethality to PARP1 inhibition. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-071. doi:10.1158/1538-7445.AM2015-LB-071
Symptom burden in gastrointestinal stromal tumors (GIST).
Authors: K. R. Gilmore, J. C. Trent, A. Garcia-Gonzalez, J. L. Williams, C. S. Cleeland, P. W. T. Pisters, L. A. Williams
Journal: Journal of Clinical Oncology (2011)

e16594 Background: The aim of this study is to define the content domain for a patient-reported outcome (PRO) measure of gastrointestinal stromal tumor (GIST) symptom burden. Symptom burden, defined as the combined impact of symptoms and treatment on daily functioning, can be an effective endpoint in clinical trials to establish treatment benefits. Methods: This is Part 1 of a study to develop a PRO GIST symptom-burden measure. Twenty patients with GIST, recruited from a clinic at MD Anderson Cancer Center, described symptoms over their disease courses in single qualitative interviews. After the interviews, patients reported symptoms experienced in the last 24 hours on the core MD Anderson Symptom Inventory (MDASI) to provide context for the analysis. Content analysis was used to identify symptoms and define content domain. Results: Mean patient age was 57.9 (standard deviation [SD] = 13.1) years, 55% were male, 40% were employed, 85% were receiving tyrosine kinase inhibitor therapy, 25% had surgery within the last 3 months, 30% had no evidence of disease, 50% had partial response or stable disease, and all had a performance status of <2 (0-5 scale). Content analysis identified 40 symptoms over the disease course, with 18 symptoms reported by > 20% of patients. Pain (75%), fatigue (65%), and peripheral edema (60%) were the 3 most commonly reported symptoms throughout the disease course. On the core MDASI, fatigue followed by drowsiness, disturbed sleep, dry mouth, and distress were the symptoms reported as occurring most often in the last 24 hours. Fatigue had the highest mean severity rating (2.35, SD = 2.43, 0-10 scale) on the core MDASI. The 40 symptoms will be reviewed by an expert panel of care providers and patients for relevance to patients with GIST. The symptoms rated most relevant will be tested for inclusion in the MDASI for GIST. Conclusions: Patients with GIST experience numerous symptoms throughout the disease course. These symptoms can cause significant interference with daily activities. The content domain for a PRO symptom-burden measure of GIST should encompass the severity and activity interference of common symptoms of GIST and its treatments and should be brief enough to allow for frequent administration to detect changes related to treatment benefits.
Prognostic Factors of Survival in Dermatofibrosarcoma Protuberans
Authors: Swathikan Chidambaram, En Lin Goh
Journal: JAMA Dermatology (2016)

To the Editor We would like to thank Criscito et al1 for their study evaluating the prognostic factors of survival in patients with dermatofibrosarcoma protuberans (DFSP). The authors conclude that age at diagnosis, male sex, and tumor size are the most valuable predictors of survival.
Abstract 5567: Anti-angiogenic activity of Thio-Cl-IB-MECA, a novel A3 adenosine receptor agonist, by regulating of PI3K/AKT/mTOR and ERK signaling pathways in endothelial cells
Authors: Jedo Oh, Gi Dae Kim, Lak Shin Jeong, Sang Kook Lee
Journal: Cancer Research (2015)

Abstract Angiogenesis is a complex process that involves sprouting of new capillaries from pre-existing blood vessels. Angiogenesis is also involved in many pathological conditions including tumor growth, diabetic retinopathy, psoriasis, rheumatoid arthritis, and atherosclerosis. In cancer, newly formed vessels not only promote tumor growth but also cause the tumor cells to become more malignant and metastatic. Therefore, angiogenesis is an attractive target for the development of a wide variety of therapies, including antitumor agents. A3 adenosine receptor (A3AR) agonists have exhibited anti-proliferative activity against cancer cells. However, anti-angiogenic effects of A3AR agonists in endothelial cells have not been investigated yet. In the present study, the potential anti-angiogenic activity and precise mechanism of action of the A3AR agonist thio-Cl-IB-MECA (TCIM) were investigated in cultured HUVECs and mouse embryonic stem cells/embryonic body (mES/EB) derived endothelial cells. TCIM inhibited migration and tube formation of endothelial cells and markedly decreased ex vivo microvessel sprouting in cultured mouse aortic rings. TCIM also suppressed the expression of the endothelial biomarker platelet endothelial cell adhesion molecule (PECAM) via regulation of PI3K/AKT/mTOR and ERK signaling in mES/EB-derived endothelial cells. Citation Format: Jedo Oh, Gi Dae Kim, Lak Shin Jeong, Sang Kook Lee. Anti-angiogenic activity of Thio-Cl-IB-MECA, a novel A3 adenosine receptor agonist, by regulating of PI3K/AKT/mTOR and ERK signaling pathways in endothelial cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5567. doi:10.1158/1538-7445.AM2015-5567