tbuckley/cabot-search huggingface dataset:
Abstract 577: The albumin to globulin ratio predicts chemotherapeutic outcomes in patients with unresectable metastatic CRC
Authors: Masatsune Shibutani, Kiyoshi Maeda, Hisashi Nagahara, Hiroshi Ohtani, Yasuhito Iseki, Tetsuro Ikeya, Kenji Sugano, Katsunobu Sakurai, Sadaaki Yamazoe, Kenjiro Kimura, Takahiro Toyokawa, Ryosuke Amano, Naoshi Kubo, Hiroaki Tanaka, Kazuya Muguruma, Masaichi Ohira, Kosei Hirakawa
Journal: Cancer Research (2015)

Abstract Background: Markers of the systemic inflammatory response have been recognized to correlate with prognosis in patients with various types of cancers. The pretreatment albumin to globulin ratio (AGR) has been reported to correlate with the long-term survival in patients with various cancers. However, there are no reports regarding the correlation between the pretreatment AGR and chemotherapeutic outcomes in patients with unresectable metastatic colorectal cancer. The aim of this study was to evaluate the prognostic significance of the pretreatment AGR in patients with unresectable metastatic colorectal cancer. Methods: A total of 66 patients with unresectable metastatic colorectal cancer who underwent palliative chemotherapy for metastatic tumors were enrolled. The AGR was calculated as follows: Albumin/(Total protein - Albumin). Results: The median pretreatment AGR was 1.254 (range: 0.849-1.840); we set 1.25 as the cut-off according to this value. Based on the cut-off value of 1.25, 34 patients were classified into the high-AGR group and 32 patients were classified into the low-AGR group. The high-AGR group had a significantly higher chemotherapeutic disease control rate (p = 0.040) and better progression-free survival (p = 0.0171) and overall survival (p = 0.0360) rates than the low-AGR group. Among the clinicopathological factors, the AGR was identified to be the only prognostic factor for progression-free survival (Hazard Ratio: 2.527, 95% Confidence Interval: 1.152-5.545, p = 0.021) and overall survival (Hazard Ratio: 1.946, 95% Confidence Interval: 1.033-3.668, p = 0.039). Conclusions: The pretreatment AGR is a useful prognostic marker in patients with unresectable metastatic colorectal cancer who receive palliative chemotherapy. Citation Format: Masatsune Shibutani, Kiyoshi Maeda, Hisashi Nagahara, Hiroshi Ohtani, Yasuhito Iseki, Tetsuro Ikeya, Kenji Sugano, Katsunobu Sakurai, Sadaaki Yamazoe, Kenjiro Kimura, Takahiro Toyokawa, Ryosuke Amano, Naoshi Kubo, Hiroaki Tanaka, Kazuya Muguruma, Masaichi Ohira, Kosei Hirakawa. The albumin to globulin ratio predicts chemotherapeutic outcomes in patients with unresectable metastatic CRC. [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 577. doi:10.1158/1538-7445.AM2015-577
Abstract 1832: Quantification of metabolic changes by magnetic resonance and mechanism of cell death in ovarian cancer
Authors: Louiza Belkacemi
Journal: Cancer Research (2015)

Abstract Quantification of metabolic changes by magnetic resonance and mechanism of cell death in ovarian cancer Louiza Belkacemia*, Leila Maurmannb and Rathindra N Bosea aDepartment of Biology and Biochemistry, University of Houston, Houston, TX 77204 bDepartment of Chemistry, Kansas State University, Manhattan, KS 6650 Ovarian cancer is the most frequent cause of death from gynecologic malignancy. Presently most ovarian cancers are diagnosed when the disease has progressed to stage III or IV. Therefore there is an urgent need for the identification of new biomarkers for early diagnosis and drug efficacy. Changes in metabolite concentrations have been associated with tumor regression or progression. Nuclear magnetic resonance (NMR) has been used to identify molecular markers during cell death (apoptosis), especially the onset of membrane disintegration. Cisplatin is the most commonly used drug in chemotherapy of ovarian cancer. To date, most research has been focused on the cisplatin-DNA reaction. Thus it is essential to evaluate the effect of cisplatin on binding to other biomolecules in the cell. Chinese hamster ovarian (CHO) cells, which, like resistant ovarian cancer cells, require high cisplatin concentrations to induce cell death, were treated with 50 μM cisplatin at different time intervals. Metabolite concentrations were determined by one and two dimensional 31P and 1H NMR. Moreover, the A2780 cisplatin-sensitive cell line and its resistant variant were evaluated for the mechanism of cell death. Analysis revealed that enhanced apoptosis was associated with significantly increased phosphocholine and glycerophosphocholine metabolites and marked elevation of cellular phosphocreatine and nucleoside triphosphate concentrations at 6 hrs and decreased thereafter. Plasma membrane alterations were paralleled by an upregulation of expression of Fas and related proapoptotic Bax and PUMA genes, and Fas and caspase-3 and -9 proteins. These findings suggest that NMR may be used as a tool to monitor tumors and drug efficacy in humans using for instance tissue biopsies. Further, NMR measurements of cell extracts may provide significant insight on pathways to apoptosis. Citation Format: Louiza Belkacemi. Quantification of metabolic changes by magnetic resonance and mechanism of cell death in 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 1832. doi:10.1158/1538-7445.AM2015-1832
Studies on the Acid Polysaccharides in Blood Vessel Walls (3) : INFLUENCE OF ACID POLYSACCHARIDES ON CAPILLARY FRAGILITY AND CAPILLARY PERMEABILITY IN EXPERIMENTAL HEMORRHAGIC DIATHESIS
Authors: Ichiteru Shishioka
Journal: Circulation (1960)

The author studied the influence of hi acid and cho sulfate on capillary fragility and permeability of guinea pigs with experimental hemorrhagic diathesis (scurvy, thrombopenic purpura, vascular purpura). Capillary permeability is determined by the concentration of T-1824 in the plasma, and capillary fragility by the Borbely negative pressure method. Capillary permeability and fragility of normal male rats did not increase or decrease by administration of hi acid or cho sulfate. The increase of capillary permeability and fragility in experimental scorbutic guinea pigs was ameliorated by administration of Vitamin C or hi acid. hi acid seemed to inhibit the increase of capillary fragility and permeability in experimental thrombopenic purpuric guinea pigs. Increased capillary fragility of experimental vascular purpura was decreased by administration of hi acid. It seemed that cho sulfate did not ameliorate the increase of capillary permeability and fragility in the experimental hemorragic diathesis. Capillary fragility and permeability were not always parallel each others. In experimental vascular purpura, when the capillory fragility began to increase, the capillary permeability decreased. The contents of acid polysaccharides in blood vessel walls in animals with experimental hemorrhagic diathesis were approximately the same as in normal animals.
Preliminary evidence of relationship between genetic markers and oncology patient quality of life (QOL)
Authors: J. A. Sloan, H. McLeod, D. Sargent, X. Zhao, C. Fuchs, R. Ramanathan, S. Williamson, B. Findlay, R. Morton, R. M. Goldberg
Journal: Journal of Clinical Oncology (2004)

5 Background: Is there a relationship between the state of cancer patients' genetic structure and their quality of life? Genetic variants have been associated with patient toxicity or clinical outcome. There has been little work done exploring the relationship between genetic variants and patient QOL. We pose the following research question: is there any association between genetic markers in folate genes with oncology quality of life outcomes? Methods: 494 patients on a GI Intergroup phase III trial of metastatic colorectal cancer to investigate the efficacy for combinations of 5-fluorouracil, irinotecan, and oxaliplatin provided their genomic DNA samples and completed QOL forms (Symptom Distress Scale (SDS) and visual analog scales). Three folate candidate genes were evaluated (DPYD, MTHFR, and TYMS). Two sample procedures examined differences in QOL between patients with genetic variants and wild-type patients. Differences of at least 10-points on a 0–100 point range were considered clinically significant and p-values < 0.05 were considered statistically significant. Results: Genetic variants in DPYD*5 and TYMS TSER produced patient groups with differences in QOL. Statistically and clinically significant differences (10.3 points; p-value 0.008) on fatigue scores were found for DPYD*5 genotype. The A/A allele of DPYD*5 had lower fatigue scores (p=0.008). The TYMS TSER marker differed on overall SDS, fatigue and on outlook score (p=0.007, 0.02, 0.007 respectively). No difference was found on MTHFR genes (p>0.05). Conclusions: Folate homeostasis is important for cellular functions. The associations between DPYD or TYMS and QOL are encouraging. There is sufficient evidence to suggest that there may indeed be a link between genetic structure and QOL. This hypothesis-generating study involved only patients with colorectal cancer, and looked at only a small number of genetic markers and specifically-targeted QOL endpoints, and yet uncovered evidence of potentially strong and specific relationships. In particular, the relationship between fatigue and genetic structure is worthy of further study. No significant financial relationships to disclose.
Efficacy and Safety of Deferasirox Across Underlying Non-Transfusion-Dependent Thalassemia Syndromes: 1-Year Results from the Thetis Study
Authors: M Domenica Cappellini, Vip Viprakasit, Yesim Aydinok, John B Porter, Yong-Rong Lai, Noppadol Siritanaratkul, Zeynep Karakas, Antonis Kattamis, Candace Wang, Zewen Zhu, Felicity Schaefer, Ali T Taher
Journal: Blood (2015)
A phase I study of temsirolimus and valproic acid for refractory solid tumors in children.
Authors: D. W. Coulter, S. H. Gold, B. Weston, I. Davis, J. Blatt
Journal: Journal of Clinical Oncology (2011)

9563 Background: Temsirolimus (Tem), an inhibitor of the mammaliantarget of rapamycin (mTOR), and valproic acid (VPA), an inhibitor of histone deacetylase (HDAC), are both inducers of autophagy. Each has shown in vitro and in vivo antitumor activity against a range of cancers. Prior pediatric studies have established a maximumtolerated dose (MTD) for Tem of 75mg/m2IV every week. We propose that the combination of Tem and VPA may have additive or synergistic activity in the treatment of pediatric solid tumors. Methods: This is a phaseI, open label dose-escalation trial to establish the MTD for Tem in combination with VPA in children and adolescents withrefractory solid tumors.Secondary aims include measurement of expression of IGF-IR, mTOR, and autophagy markers on archival tumor tissue; HDAC activity in peripheral blood mononuclear cell samples at serial times on therapy; pharmacokinetics (PK) of Tem; and tumor response. Patients 2-18 years old with refractory solid tumors and measurable disease by RECIST criteria are started on oral VPA (5mg/kg PO TID) with a target serum level of 75-100 ng/ml. Tem was started at an initial dose of 60mg/m2/week. PK sampling is performed in weeks 1 and 5. Results: To date 4 patients have been enrolled (Table). Of the first 3 patients, two experienced dose-limiting toxicity (grade 3 mucositis). Pt 4 tolerated a Tem dose of 35mg/m2/week. Accrual is ongoing at this dose level. Conclusions: Definition of the MTD for Tem in combination with VPA is pending but appears to be significantly lower than that of Tem alone in the pediatric age group. Preliminary data suggest that the combination may have activity in melanoma and ASPS. This study is supported by Pfizer and The University of North Carolina at Chapel Hill Clinical and Translational Research Center. Characteristics of study subjects to date. Patient Diagnosis Dose/m2 DLT Response 1 ASPS 60 No OR 2 C-spine ependymoma 60 Mucositis OR 3 Melanoma 60 Mucositis PR 4 Soft tissue sarcoma NOS 35 No PD Abbreviations: ASPS, alveolar soft parts sarcoma; NOS, not otherwise specified; OR, objective response; PR, partial response; DLT, dose-limiting toxicity.
Elevated MIBG Activity at the Site of Erythema of Unknown Etiology
Authors: Peng Xie, Robert Monaghan, Kevin Edwards, Fuqiang Shao, Hongming Zhuang
Journal: Clinical Nuclear Medicine (2016)

A 6-year-old boy underwent 131I-MIBG therapy for recurrent neuroblastoma. On posttherapy scan, there were new foci of increased MIBG activity in the anterior abdomen, which were not seen on pretherapy 123I-MIBG scan. Physical examination demonstrated that these new foci of activity corresponded to the sites of asymptomatic erythema, which had of unknown etiology and was spontaneously resolved without treatment.
PTH-060 Clinical benefit of dietary advice in ulcerative colitis: results of a pilot study
Authors: T A Moshkovska, J F Mayberry
Journal: Gut (2010)

<h3>Introduction</h3> The subject of diet and ulcerative colitis is controversial. Patients believe dietary factors are important. Some research suggests dietary modification can bring real benefit to patients with UC. However, recognised dietary guidelines for use in UC do not exist. An educational booklet <i>Diet and Ulcerative Colitis</i> developed from preliminary focus group data (supported by an educational grant from P&amp;G pharmaceuticals), provided dietary principles and advice for UC flare-ups and was based on a high protein, low fat, low carbohydrate and low fibre diet. <h3>Methods</h3> The purpose of the pilot study was to test the efficacy of dietary modification in UC. The standardised dietary advice booklet <i>Diet and Ulcerative Colitis</i> was given to 64 UC patients. Disease activity was assessed using Simple Clinical Colitis Activity Index (SCCAI), gastrointestinal symptom-specific anxiety was determined using Visceral Sensitivity Index (VSI) and a study designed food frequency questionnaire was used to measure compliance with dietary advice. Symptoms were reassessed by repeated completion of SCCAI, VSI and food frequency questionnaire after 6 months. <h3>Results</h3> The mean age of participants was 48 (range 22–81 years). 47% of participants were male. 73% of the sample was Caucasian, 27% South Asian. On entry to the study, 55% participants had a high VSI—the level of gastrointestinal symptom-specific anxiety, 33% had a moderately high VSI and 13% (eight people) did not show any symptom-specific anxiety. Paired t test showed that compliance with dietary advice was associated with a significant decrease in SCCAI (t=2.5364, p=0.007) and highly significant in the reduction of VSI (t=−4.5351, p&lt;0.0001). Correlation between SCCAI and VSI was significant (p&lt;0.01). It appeared that patients9 symptom-anxiety level is directly dependent on the severity of symptoms in UC. Thirteen participants (20%) with the highest clinical activity (SCCAI range 5–12) noted significant reduction of the symptoms severity, following dietary advice (SCCAI range 2–8). 74% of study participants found dietary advice helpful and 54% of UC patients reported feeling more confident about controlling diarrhoea, bloating and pain. 98% of patients reported that information given in the booklet was easy to read and understand. <h3>Conclusion</h3> This dietary advice was viewed by patients as beneficial in overcoming symptom-specific anxiety and effective in self-management of UC symptoms, especially during flare-ups. We conclude that dietary modification should be considered as an additional therapeutic factor in UC treatment.
Abstract 4880: Characterization of genetic concordance between primary tumor cells, circulating tumor cells, and metastatic tumor cells from patients with prostate cancer
Authors: Lixin Yang, Linling Chen, Yafan Wang, Jeremy Jones, Yun Yen, Sofia Loera, Raju Pillai, Peiguo Chu, Dennis Weisenburger
Journal: Cancer Research (2015)

Abstract Circulating tumor cells (CTCs) which disseminate from the primary tumor site have been found to be a major source of metastatic tumor. However, CTCs are heterogeneous and most CTC DNA is fragmented due to apoptosis. To better understand the molecular pathogenesis of metastasis, it is imperative to obtain single, non-apoptotic CTCs and investigate the genetic concordance between primary tumor cells, CTCs and metastatic tumor cells. Due to the abundance of normal cells present in the blood and in tumor tissue, isolation of single tumor cells or pure cell populations of these cells is extremely difficult. The DEPArray platform is designated to collect single CTCs after Cell-Search enrichment, and to sort pure intact tumor cells from formalin-fixed, paraffin-embedded (FFPE) tissues. Taking advantage of this technology, we have isolated single CTCs from prostate cancer patients. Whole genome amplification was performed and genomes with high integrity were used to evaluate the hotspot mutations in PIK3CA. For comparison, we also made single cell suspensions from FFPE tissue blocks of primary tumors and metastatic tumor in lymph nodes from the same patients. Immunofluorescence staining for cytokeratin (CK) and vimentin (Vim) was performed, followed by isolation of pure tumor cells (CK+), stromal cells (Vim+) and double-positive cells (CK+/Vim+) from both primary tumor and lymph node samples. We plan to do genetic analysis on these cells and compare the results to determine the genetic concordance between primary tumor cells, CTCs and metastatic tumor cells. By using the DEPArray, we have successfully isolated single CTCs, and populations of tumor cells, stromal cells and double-positive cells from primary and metastatic tumors. We will present new data on the genetic concordance between these cells, which will provide new insight into our understanding of metastasis in prostate cancer. Citation Format: Lixin Yang, Linling Chen, Yafan Wang, Jeremy Jones, Yun Yen, Sofia Loera, Raju Pillai, Peiguo Chu, Dennis Weisenburger. Characterization of genetic concordance between primary tumor cells, circulating tumor cells, and metastatic tumor cells from patients with prostate 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 4880. doi:10.1158/1538-7445.AM2015-4880
Abstract 3312: Growth inhibition of cancer cells by 5-aminolevulinic acid
Authors: Toshikatsu Horiuchi, Yusuke Serizawa, Syoichiro Tateishi, Keiichi Iwaya, Junichi Watanabe, Shinichi Kobayashi, Ken Sato, Fumihiko Kimura, Nariyoshi Shinomiya, Yuji Morimoto
Journal: Cancer Research (2015)

Abstract Introduction: 5-aminolevulinic acid (ALA) is intracellularly metabolized to protoporphyrin IX (PpIX) in heme synthetic pathway. As PpIX is a fluorescent photosensitizer and has been shown to accumulate preferentially in cancer cells, exogenously administered ALA is used for photodynamic diagnosis (PDD) and photodynamic therapy (PDT). However, the influence of exogenously administered ALA on cellular proliferation is not elucidated. Overproduction of heme owing to exogenously administered ALA may induce an upregulation of heme oxygenase (HO-1), which is a potential inhibitor of cellular proliferation via a generation of carbon monoxide (CO) and an induction of P21. We therefore examined cytotoxicity when I was administered. Methods and Materials: Human cancer cell lines (10 types) and human normal cell lines (2 types) were incubated with ALA (1.0 mM) for 24 hrs. A fluorometric measurement for PpIX (ex. 405 nm. em. 630 nm) and a proliferation assay using WST-8 were carried out. The expression of HO-1 was evaluated using Western blotting. Results: In 8 out of 10 cancer cell lines, an amount of intracellularly synthesized PpIX after the administration of ALA was highly correlated with a decrease in number of cells (cell death) (R = 0.73), and two out of the eight cell lines (HepG2 and Caki-1) showed a significant reduction in number of cells (&amp;gt; 15%) accompanied with a significant increase in PpIX generation (&amp;gt; 90 a.u.). On the other hand, normal cell lines (HUVEC, SMC) showed less changes in cell count (within 1.5%) accompanied with less PpIX generation (within 35 a.u.). The HO-1 production rate, defined by HO-1 expression level in ALA-treated cells / HO-1 expression level in non-treated cells was highly correlated with the cell death (R = 0.67). Conclusion: In some types of cancer cell lines, an exogenously administered ALA leads to cell death, probably due to the upregulation of HO-1 that is produced by the accumulation of PpIX. Meanwhile, in normal cell lines, the exogenously administered ALA is less likely to induce cell death. Citation Format: Toshikatsu Horiuchi, Yusuke Serizawa, Syoichiro Tateishi, Keiichi Iwaya, Junichi Watanabe, Shinichi Kobayashi, Ken Sato, Fumihiko Kimura, Nariyoshi Shinomiya, Yuji Morimoto. Growth inhibition of cancer cells by 5-aminolevulinic acid. [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 3312. doi:10.1158/1538-7445.AM2015-3312
Abstract 1711: SLC6A15, a novel potential metabolic target for non-small cell lung cancer
Authors: PALLEVI SRIVASTVA, Hyuntae Yoo
Journal: Cancer Research (2015)

Abstract Current therapeutic targets for non-small cell lung cancer consist only of signaling pathways targeting VEGF, EGFR or ALK. Recent researches have put focus on understanding cancer metabolism (such as 2-hydroxyglutarate accumulation in gliomas with mutant IDH1) and have opened a new avenue in cancer therapeutics which can complement the current practices. Here we introduce a new potential metabolic target for non-small cell lung cancer, SLC6A15. It is a trans-membrane protein known to facilitate uptake of branched chain amino acids (BCAA) (leucine, isoleucine and valine) and proline into the cells. BCAA was recently reported to increase cellular proliferation by regulating m-TOR in normal cells like beta-pancreatic cells. Here we show that these BCAA are highly enriched in lung tumor cell lines (H1299 &amp; H460) as well as in human lung tumor tissues as a result of overexpression of SLC6A15. We performed a transient knockdown of this transporter using siRNA for SLC6A15 and observed its effect on reduced clonogenicity of the two cancer cell lines by 3.3 and 1.6 fold, respectively. Further, gas chromatography mass spectrometry (GC-MS) analysis of the cells treated with si(SLC6A15) revealed selective reduction of BCAA levels by 1.3 to 1.5 fold but not in Proline, which can be synthesized in the cells unlike BCAA. These results support the role of these amino acids in tumor cell proliferation. Overexpression of SLC6A15 protein was confirmed by western blot analysis in 8 NSCLC cell lines and is indicative of its tumor specific nature. This finding is also supported by SLC6A15 gene expression data available on TCGA (The Cancer Genome Atlas), where 6 out of 10 patients show high expression of this gene. Therefore, we conclude that SLC6A15 is a new candidate of therapeutic target for NSCLC. Targeted inhibition may open new possibilities to specific reduction of tumor cell proliferation and possibly, increase life expectancy of patients suffering from NSCLC. Citation Format: PALLEVI SRIVASTVA, Hyuntae Yoo. SLC6A15, a novel potential metabolic target for non-small cell lung 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 1711. doi:10.1158/1538-7445.AM2015-1711