tbuckley/cabot-search huggingface dataset:
Abstract 2023: Isolation of breast tumor initiating cells (TICs) by exogenous delivery of the OCT4 transcription factor
Authors: Adriana S. Beltran, Bryan Richarson, Ashley Rivenbark, Patricia Casbas-Hernandez, Xinni Yang, Pilar Blancafort
Journal: Cancer Research (2011)

Abstract Tumor Initiating cells (TICs) are being extensively studied for their role in tumor etiology, maintenance and resistance to treatment. Herein, we describe a novel approach to generate TICs by transduction of human primary breast cell preparations with exogenous expression of the OCT4 transcription factor. The OCT4 transduced breast colonies (OTBCs) underwent an immortalization process, as reflected by loss of p16 and enhanced telomerase expression. OTBCs exhibited cancer stem cell antigens, such as CD44high/CD24low/-. Consistently, these cells generated subcutaneous tumors in nude mice with colonization capabilities. As little as 1-50 cells were sufficient to induce tumor formation and thereby these cells had TIC properties. Histological analysis of these tumors revealed poorly differentiated breast carcinomas. RNAi-mediated knock-down of OCT4 and downstream embryonic targets of OCT4, resulted in suppression of the self-renewal ability, suggesting that this phenotype was dependent on OCT4. Genome-wide microarray analysis supported the finding that OCT4 over-expression in these clones was molecularly associated with Epithelial-to-Mesenchymal Transition (EMT) gene signatures and strongly correlated with the claudin-low intrinsic subtype of breast cancer. Our experimental approach provides a novel model system to dissect genes, small RNAs and small molecules that could be used to effectively target breast cancer self-renewal and tumor initiation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2023. doi:10.1158/1538-7445.AM2011-2023
Abstract 4282: The role of glycosphingolipids in the formation of cancer stem cells and drug resistance
Authors: Vineet Gupta, Gauri Anand Patwardhan, Xin Gu, Brian Rowan, Michal Jazwinski, Yong Yu Liu
Journal: Cancer Research (2010)

Abstract Tumorigenesis and malignant progression of cancers rely on a small subset of cells known as cancer stem cells (CSCs). In addition to forming primary tumors, metastasis and relapse, CSCs always display resistance to cytotoxins and this resistant feature protects CSCs during the course of chemotherapy. Glucosylceramide synthase (GCS) is a limited enzyme catalyzing the first glycosylation in glycosphingolipids synthesis. Glycosphingolipids are likely to play an essential role in maintaining the stemness of stem cells, since that deletion of GCS induces apoptosis of embryonic stem cell and stops embryo development in GCS knockout mice. The stage-specific embryonic antigens (SSEA-3, SSEA-4) are glycosphingolipids and serve as common pluripotent markers for human embryonic stem cells. In the present study, we have found that GCS modulates the formation and maintenance of breast cancer stem cells. GCS overexpression was interrelated to the increase of breast cancer stem cells (BCSCs) and drug resistance in human breast cancer MCF-7 cell lines after doxorubicin induction. In MCF-7/Dox (doxorubicin-resistant) cells, GCS protein was increased by 39-fold accompanied with enhanced enzyme activity, as compared to wild-type MCF-7 cell. Analyzed by using flow cytometry and immunostaining, the BCSCs with CD44+/CD24-/ESA+ phenotype were increased by 5-fold, and 3-fold in MCF-7/Dox and NCI-ADR/RES cell lines, as compared to MCF-7 cell lines, respectively. In BCSCs, GCS enzyme activity was 2-fold greater than other populations sorted from MCF-7/Dox. Silencing GCS by using mixed-backbone oligonucleotide (MBO-asGCS) significantly decreased the numbers of BCSCs in MCF-7/Dox cells. We observed tumorigenesis of NCI/ADR-RE/GCS (GCS overexpressed) and NCI/ADR-RE/asGCS (GCS silenced) in athymic nude mice. Aggressive tumors were found in all mice inoculated with NCI/ADR-RES and NCI/ADR-RE/GCS cells that were BCSC-enriched; however, no tumor or metastasis was observed in mice injected with NCI-ADR/asGCS cells. Furthermore, MBO-asGCS treatment (1 mg/kg) significantly decreased the numbers of BCSCs isolated from tumors of NCI-ADR/RES, as compared with control groups. Furthermore, BCSCs after MBO-asGCS treatment were more sensitive to doxorubicin. These results, for the first time, demonstrate that glycosphingolipid is involved in the regulation of cancer stem cell formation. Silencing GCS eliminates BCSCs, that can reverses drug resistance as well as prevent tumor relapse. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4282.
Estradiol downregulates miR-21 expression and miR-21 gene targets in MCF-7 breast cancer cells.
Authors: NS Wickramasinghe, TT Manavalan, KA Riggs, Y Li, CM Klinge
Journal: Cancer Research (2009)

Abstract Abstract #3051 Select changes in microRNA (miRNA) expression correlate with diagnostic markers used in breast cancer therapies, e.g., estrogen receptor α (ERα) and tumor grade. However, no one has examined how estradiol (E2) regulates miRNA expression in breast cancer cells. Here miRNA microarrays were used to identify miRNA genes regulated by E2 in MCF-7 breast cancer cells. Twenty-five miRNAs were E2-regulated and select results were confirmed by quantitative-PCR. E2 reduced the expression of miR-21, an oncogene, and repression was inhibited by the antiestrogen ICI 182,780, ERα knockdown by siRNA, and by pre-treatment with Actinomycin D or cycloheximide. Thus, E2-ERα reduces miR-21 expression by primary transcriptional and secondary target activities. The effect of E2 on luciferase reporters containing the miRNA recognition elements (MREs) from the 3'-UTRs of 8 putative miR-21 regulated genes: CCM1, SKI, TGFB1, PDCD4, RAB6A, RAB6C, RASA1, and RASGRP1 was tested in MCF-7 cells. E2 increased luciferase with the MREs from TGFB1, PDCD4, RASA1, and RASGRP1, and from the full length 3' UTR of the PDCD4 gene, consistent with an E2-mediated decrease in miR-21 resulting in increased stability of Renilla mRNA and increased luciferase activity. Antisense to miR-21 increased luciferase from the TGFB1,PDCD4, RAB6A, and RASGRP1 reporters, consistent with these MREs being bona fide miR-21 targets. The E2-mediated decrease in miR-21 correlated with increased expression of miR-21-targets PDCD4, PTEN, and Bcl-2 at the protein level and these increases were blocked by AS to miR-21 and by siRNA knockdown of ERα. These results identify miR-21 as an ERα- regulated miRNA in MCF-7 cells. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3051.
SEGUIMIENTO DE PÓLIPOS DE COLON DE TAMAÑO SUPERIOR A 10 MM: ANÁLISIS RETROSPECTIVO DE UNA SERIE LOCAL
Authors: C González-Artacho, C Alegria-Motte, E Redondo Cerezo, JG Martínez Cara, M López De Hierro, J De Teresa Galván
Journal: Endoscopy (2013)

Introducción: Los pólipos > 10 mm aumentan el riesgo de recurrencia de adenoma avanzado. La colonoscopia es segura y eficaz para detectar adenomas colorrectales y la polipectomía endoscópica se ha demostrado eficaz en prevenir la progresión a adenocarcinoma. Objetivo: Analizar las características, tratamiento y seguimiento de pólipos > 10 mm. Material y Método: Revisión retrospectiva durante tres años, de colonoscopias con pólipos > 1 cm. Analizamos variables demográficas, características de las lesiones y seguimiento/actitud terapéutica. Resultados: Detectamos 38 lesiones; 65.8% en varones, y edad media de 62 ± 13 años. Indicación: Rectorragia (36.8%), antecedentes familiares de CCR (7.9%), CCR intervenido (5.3%), alteración del ritmo intestinal (5.3%) y estreñimiento (5.3%). Tamaño: 20 ± 8.6 mm. Histología: Adenoma velloso 40.54%, pólipo hiperplásico 18.94%, tubulovelloso 13.51%, tubular 13.51%, adenomatoso 10.81%, con displasia moderada 10.81%, grave 5.41% y adenocarcinomas moderadamente diferenciados 5.41%. Tratamiento: Polipectomía con asa (50%), resección mucosa tipo piece-meal (36.8%), resección mucosa en un tiempo (7.9%). Se intervinieron quirúrgicamente 10.5%: Dos displasias moderadas, una grave, y un adenoma velloso de 35 mm. El 63.2% se siguió endoscópicamente con intervalo de tiempo medio de un año. El 18.4%, pólipos hiperplásicos excepto un adenoma velloso en un paciente de edad avanzada, no se registró seguimiento. De los adenocarcinomas moderadamente diferenciados, uno continuó revisiones endoscópicas sin recidivas y en el otro se cesó por edad avanzada del paciente. Conclusiones: -Los pólipos serrados son los precursores de aproximadamente un tercio de los CCR, y en nuestra serie es llamativa la ausencia de éstos informados por el patólogo. -Probablemente los pólipos hiperplásicos descritos pertenecen a esta variedad, que sigue una vía de transformación carcinomatosa diferente, así que es imprescindible un adecuado estudio histológico, detección y revisiones endoscópicas. -En la mayoría de hiperplásicos > 10 mm no se realizó seguimiento. Teniendo en cuenta que representan el 70 – 95% de los pólipos serrados, sería conveniente realizar revisión endoscópica a los 3 años.
Middle-Lobe Syndrome
Authors: Gustaf E. Lindskog, Harold C. Spear
Journal: New England Journal of Medicine (1955)

A TELECTASIS with chronic pneumonitis involving the right middle lobe has received considerable attention since this phenomenon was classified as a clinicopathological entity called "middle-lobe syndrome" by Graham, Burford and Mayer1 in 1948. These investigators presented a group of 12 cases of presumably nontuberculous atelectasis and chronic pneumonitis involving the right middle lobe, each secondary to compression of the middle-lobe bronchus by enlarged lymph nodes. The authors pointed out that any inflammatory process leading to lobar hilar lymphadenopathy may result in bronchostenosis, with consequent atelectasis and pneumonitis. More than a decade before, Brock et al.2 (1937) had stressed the possibility . . .
Abstract 4449: Deep penetration of PDT drugs into tumors via non-covalent drug-gold nanoparticle conjugates
Authors: Joseph D. Meyers, Yu Cheng, Ann-Marie Broome, Malcolm E. Kenney, Clemens Burda, James P. Basilion
Journal: Cancer Research (2011)

Abstract In 2010, more than a million new cancer cases are expected to be diagnosed with half resulting in death, at an NIH estimated total yearly cost of $263.8 billion. Therefore, there is a critical need to improve both cancer diagnostics and therapeutics; future theranostics aim to combine both in a single visit. Consequently, efficient delivery of hydrophobic, theranostic drugs is necessary. This study presents a novel non-covalent PDT cancer drug-gold nanoparticle (Au NP) conjugate system that is able to perform rapid drug release deep into tumors within hours rather than days. The drug delivery mechanism of the PDT drug Pc 4 using Au NPs into tumors by passive accumulation was investigated via fluorescence imaging of Pc 4, elemental gold analysis, and histological staining. The pharmacokinetics of the conjugates over a 7 day period showed rapid drug excretion, as monitored via the fluorescence of Pc 4 which decreased significantly to near baseline levels. Moreover, the biodistribution of Au NPs indicated clearance of the conjugates from the mice. The spleen, liver, kidneys, and urinary tract showed accumulation of Au NPs and accounted for 33.6% of the injected dose at only 4 hrs, suggesting possible excretion pathways, since the total injected dose of Au NPs recovered from dissected organs decreased by 33.4%. Histological analysis corroborated these findings; Au NPs in the liver were found in liver sinusoids and hepatocytes, Au NPs in the spleen were found near macrophages, Au NPs in the kidney were located in the glomerulus, and Au NPs in the urinary tract were found in the stroma. At 4 hrs post-injection, ∼76% of the injected dose of Au NPs was recovered in harvested organs, and AuNPs accumulated passively in tumors with an average accumulation of 8 ± 6 % ID (or ∼62.46 μg/g of tumor tissue). The tumor (4 hrs post-injection) showed very high fluorescence intensities further suggesting the passive accumulation of Pc 4 via the Au NPs within the tumor. In vitro studies showed the conjugates delivered 389.4 moles of Pc 4 per mole of Au NP into cells in 4 hrs; in vivo studies showed approximately 10 RFUs (of Pc 4)/ μg of gold delivered into tumor tissues. Ultimately, this study suggests that Pc 4 non-covalently loaded Au NPs that penetrate deep into the tumor interior provide a very attractive approach to delivery cancer drugs to visualize carcinomas and track therapeutic responses. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4449. doi:10.1158/1538-7445.AM2011-4449
Reply to Ustundag et al.
Authors: M. Ikeda, I. Maetani
Journal: Endoscopy (2011)

There may be cases in which it is difficult to open the forceps due to the form of the tumor, such as those in which the entire bile duct is strictured. In this study, we did not encounter such a case and thus found no difficulty using the method. However, we took care to open the forceps cup in the duct sufficiently before the stricture. Two cases were diagnosed based on clinical course without histology in this study. One of the cases investigated was a recurrence of lymphadenopathy in a 43-year-old male after gastric cancer resection. A definitive diagnosis of the gastric cancer was established by surgery. We could not obtain the tissue but diagnosed it as a recurrent lymphadenopathy based on image observations and the clinical course. Another case was a 69-year-old female patient with pancreatic cancer diagnosed by computed tomography to have locally advanced pancreatic head cancer invading the common bile duct, the portal vein, and the superior mesenteric artery. Placement of a biliary stent and chemotherapy were performed, and the patient died 8 months later due to progression of the pancreatic cancer, which was diagnosed based on the image observations and the clinical course.
Association between prior history of cholecystectomy and hepatocellular carcinoma (HCC) development: A case-control study in the United States.
Authors: H. M. Hassabo, A. O. Kaseb, M. A. Shama, J. Vauthey, R. D. Lozano, S. A. Curley, D. Li, M. Hassan
Journal: Journal of Clinical Oncology (2010)

e14643 Background: The incidence of HCC has increased in the USA over the past 2 decades. Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) are the most established risk factors. However, in the United States, approximately 60% of HCC patients are not attributed to viral infection. Despite the sufficient evidence that cirrhotics patients experienced high frequency of cholelithiasis, the relationship between cholelithiasis and HCC has never been examined. Methods: We conducted a hospital-based, case-control study involving 460 patients with HCC and 1104 healthy controls. Subjects were interviewed for several risk factors of HCC. Cases and controls were interviewed for prior history of cholecystectomy, age and duration of cholecystectomy. Unconditional logistic regression was used to determine adjusted odds ratios (AORs) by the maximum-likelihood method. Results: The prevalence of cholecystectomy was 36% (n = 166) among HCC patients and 11.8% (n = 130) among control subjects yielding a statistical significant crude odds ratio of 4.2 (3.3-5.5). Adjustment for the confounding effect of HCV, HBV, alcohol drinking, cigarette smoking, family history of liver cancer, diabetes mellitus and hypothyroidism indicated a significant association between prior history of cholecystectomy and HCC (AOR = 5.2 [3.7-7.3]). According to the duration of cholecystectomy; the estimated multivariate AORs and 95% CI were 7.3 (4.4-12.2), 2.7 (1.3-5.3), and 2.5 (1.4-4.3) for ≤ 3 years, 4-10 years, and > 10 years prior to HCC diagnosis or control recruitment. Among HCC patients with prior history of cholecystectomy, total of 76 patients performed cholecystectomy concurrently with tumor resection. By excluding these patients from analysis, results indicated that patients with long term prior history of cholecystectomy had 2.6 fold increase in HCC risk as compared to those without prior cholecystectomy; AOR = 2.6 (1.8-3.8). Conclusions: While we can not determine whether cholelithiasis is a risk factor of HCC development or a consequence of the underlying chronic liver diseases, we believe that underlying inflammation in patients with long-term gallstones may play a role in HCC development. No significant financial relationships to disclose.
<i>Strongyloides stercoralis</i>ileitis detected by double-balloon endoscopy
Authors: W. Hsu, S. Yang, Y. Su
Journal: Endoscopy (2009)

A 52-year-old man was admitted for chronic diarrhea since more than a year, and progressive low-leg edema over the past three months. His history revealed that he made several short-term trips to southern China for business. He was passing loose stool seven to eight times every day. Laboratory tests revealed a total leukocyte count of 10.5 × 109/L with 59.7 % neutrophils, 1.5 % eosinophils, and 30 % lymphocytes. His serum albumin level was 11.5 g/L and serum IgE level was 739 IU/mL (normal range < 78 IU/mL). The serum human immunodeficiency virus (HIV) antibody status was negative. Small-intestine follow-through study showed long-segment narrowing of the lumen of the terminal ileum ([Fig. 1 a]), whereas abdominal computed tomography demonstrated diffuse wall thickening of the terminal ileum ([Fig. 1 b]). Double-balloon enteroscopy was carried out via the anal route to further explore the long-segment narrowing in the ileum. There was loss of the normal villous structure of the terminal ileum on washing with water ([Fig. 2 a]), and widespread swelling and erosions with petechiae were noted in the mucosa after air inflation ([Fig. 2 b]; [Video 1]). Histopathological examination of biopsy specimens of this area revealed marked leukocytic infiltration, with eosinophils in the lamina propria ([Fig. 3 a]). Parasitic ova and larvae, morphologically resembling the filariform larvae of Strongyloides stercoralis, were found within the intestinal crypts ([Fig. 3 b]). The patient subsequently received treatment with ivermectin (12 mg/day) for 3 days. The diarrhea gradually resolved and the serum albumin level rose to 31.2 g/L 4 months after drug treatment.
Abstract LB-51: Breast cancer survivorship in women younger than 45 years
Authors: Courtney Preusse
Journal: Cancer Research (2012)

Abstract Since opening its doors in 1975, the Fred Hutchinson Cancer Research Center has served as a world leader in advancing the prevention, diagnosis and treatment of cancer and related diseases as causes of human suffering and death. Breast cancer has long been a strong focus of the center. Our Consortium Breast Cancer Research Program initiated over 15 years ago, fosters novel and interdisciplinary work amongst world-renowned scientists and the clinical community that examines the physical, psychological, social and economic effects of cancer treatment. Moreover, our survivorship program, as part of the LIVESTRONG Survivorship Center of Excellence Network, promotes health-protective behaviours and helps survivors and doctors understand, prevent and manage these effects. Despite this wealth of knowledge, I submit that there is a sheer lack of credible breast health resources and there are countless missed opportunties to improve upon surveillance of a sizeable yet largely underrepresented population due to perceived rarity of cancer in young women. Breast cancer knows no boundaries; it does not discriminate on the basis of age. Specific, unique and neglected concerns facing young women with breast cancer must be addressed through new directions in research; first, so as to represent the entire population of survivors rather than a subset and, second, to close critical gaps in knowledge. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-51. doi:1538-7445.AM2012-LB-51
Elevated HIF-1α Levels in CLL B Cells May Explain Their Autocrine VEGF Secretion.
Authors: Yean K. Lee, Tait Shanafelt, Denise Chan, Amato Giaccia, Debabrata Mukhopadhyay, Cristian Taccioli, George Calin, Carlo Croce, Neil E. Kay
Journal: Blood (2006)
Abstract 141: Epigenetic silencing of miR-122 in hepatocellular carcinoma
Authors: Kyoungsub Song, Chang Han, Tong Wu
Journal: Cancer Research (2012)

Abstract It has been reported that miRNAs potently influence cellular function through the regulation of extensive gene expression networks and most tumors are characterized by globally diminished miRNA expression. However, the potential mechanism of microRNA expression change in tumorigenesis remains to be further investigated. In this study, we focus on the epigenetic regulation of miRNA expression in hepatocellular carcinoma. We first performed miRNA microarray analysis in HepG2 cells, which reveals significant changes in miRNA expression profiling with 23 upregulated miRNAs and 15 downregulated miRNAs induced by the treatment with 5′aza-2′deoxycytidine (5′-aza, DNA methylation inhibitor) and 4-phenylbutyric acid (PBA, histone deaceltylation inhibitor). Interestingly, miR-122, the most abundant miRNA in the liver, is upregulated by 5′-aza and PBA, which is validated by qRT-PCR analysis in both HepG2 and Huh7 cells. In addition, miR-122 expression is increased by the overexpression of PPARγ or the treatment of PPARγ agonist (15-keto PGE2 or 15d-PGJ2).We then demonstrate that peroxisome proliferator-activated receptor gamma (PPARγ) and retinoid X receptor alpha (RXRα) bind to conserved DR-1 and DR-2 (peroxisome proliferator-activated response element) in the miR-122 promoter region and these bindings are significantly increased by 5′-aza and PBA with the biotinylated oligonicleotides precipitation assay. However, 5′-aza and PBA inhibit the binding of N-CoR (nuclear receptor corepressor) or SMRT (silencing mediator for retinoid and thyroid hormone receptor) to DR-1 or DR-2. And we found that 5′-aza and PBA inhibit PPARγ/N-CoR/SMRT protein complex formation in HepG2 cells with the immunoprecipitation assay. Furthermore, we observe that SUV39H1(H3K9 methyl transferase) protein is decreased by the co-treatment of 5′aza and PBA; and the suppression of endogenous SUV39H1 expression with SUV39H1siRNA increases miR-122 expression. Taken together, our results suggest that histone acethylation and demethylation lead to the release of PPAR-gamma from PPAR-gamma/N-CoR/SMRT protein complex to activate miR-122 transcription and to the inhibition SUV39H1 protein expression for the elimination of histone methylation to further facilitate miR-122 transcription. In conclusion, Epigenetic silencing is one of the most important mechanisms for diminished miR122 expression in hepatic carcinogenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 141. doi:1538-7445.AM2012-141