tbuckley/cabot-search huggingface dataset:
18F-FDG PET/CT in a Rare Malignant Extraskeletal Osteosarcoma
Authors: Qi Cao, Minh Lu, Thomas Huebner, Vasken Dilsizian, Wengen Chen
Journal: Clinical Nuclear Medicine (2013)

Extraskeletal osteosarcoma (EO) is a rare malignancy and its FDG PET/CT imaging is seldom reported. We present staging and restaging images of a FDG PET/CT imaging in an EO originating from paraspinous musculature. Initial staging FDG PET/CT scan showed increased metabolism of a mass in the right paraspinous region without nodal or distant metastasis. The patient underwent tumor resection and radiation therapy with a pathological diagnosis of EO. Restaging FDG PET/CT imaging demonstrated postsurgical changes without nodal or distant metastasis. This case demonstrates the clinical relevance of FDG PET/CT imaging for staging and restaging EO.
Abstract P6-06-53: Ki67 labelling index (Ki67LI) can subdivide homogeneous HER2 negative luminal grading groups (HNL-GG) in distinct biological entities
Authors: A Ferro, LM Russo, C Eccher, R Triolo, M Barbareschi, A Caldara, M Dipasquale, E Galligioni
Journal: Cancer Research (2013)

Abstract Background: Several studies have emphasized Ki67LI biologic and prognostic value and its potential application of its assessment in routine practice, particularly to define prognostic subgroups of luminal/hormone receptor-positive (HR+) tumors. Methods: Ki67LI was identified by immunohistochemical staining in 3760 EBC pts treated from 1995 to 2008. Median age was 61 y. The relationship with clinic-pathological parameters and the prognostic significance of KI67LI were investigated in all EBCs and in HER2 negative luminal (2380 HNL) cases stratified on homogeneous grading (594 G1, 1282 G2, 504 G3). Results: Median Ki67LI values were 22% in all cases, 20% in HNL and 10, 20 and 35% in different HNL grading group (HNL-GG). Ki67LI &amp;gt; 22% (1873 pts) was significantly (p&amp;lt;0.001) associated with younger age, ductal type, greater size, positive N, poor G, absent or low ER /PR expression, positive HER-2, triple negative subtypes. Local and Distant Relapses were 138 (7.3%) and 355 (18.9%) in &amp;lt; or &amp;gt; 22% Ki67LI respectively. Median time to first event was 31.7 ms in &amp;gt; 22% vs 50.1 ms in &amp;lt; 22% Ki67. At median f-up of 77 months EFS and OS were 91.9 and 92.1% in &amp;lt; 22% vs 78.9% and 81% in &amp;gt; 22% Ki67 respectively (p &amp;lt;0.001). Prognosis in term of DFS and OS was consistently worse for &amp;gt; 22% compared to &amp;lt; 22% Ki 67 in all clinical-pathological subsets, except in negative ER group. In multivariate analysis, KI 67mantained an independent prognostic significance for DFS and OS. In HNL, EFS and OS were 93.7 and 92% in &amp;lt; 20% vs 81.7 and 83.3% in &amp;gt;20% Ki67(p &amp;lt;0.001). Using median ki67LI value for different homogenous HNL-GG as cutoffs, we stratified these populations in low and high risk. The results are shown in the following table. Stratification in high and low risk subgroups of homogeneous HNL-GGSubgroupsEFSpOSpG1 high91.7%0.04392.7%0.114G1 low96.0% 96.0% G2 high84.2%&amp;lt;0.00187.5%0.012G2 low93.7% 90.6% G3 high70.9%0.05376.4%0.036G3 low83.2% 80.7% Conclusions: Our study confirms prognostic value of Ki67LI in EBC, associated with other clinical-pathological characteristics. Cutoffs are different into HNL-GG. They can cathegorize at least two biological entities in every grading group providing additional prognostic information in planning therapies and outcome prediction. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-06-53.
Good fences make good neighbors
Authors: Hannah L. Turner, Jerrold R. Turner
Journal: Gut Microbes (2010)

The gastrointestinal lumen is home to over 400 species of microorganisms. The composition of this microbial community varies along the length of the gastrointestinal tract as a function of regional epithelial secretory activity as well as diet and other defined and undefined determinants. Improved understanding of the factors that impact luminal microbial populations and development of means to modulate gut microbes for therapeutic benefit hold great promise. The gastrointestinal epithelium, which regulates interactions between microbes and the mammalian host, is the topic of this review.
PROGNOSTIC VALUE OF CORONARY COMPUTED TOMOGRAPHY ANGIOGRAPHY DURING 5 YEARS OF FOLLOW UP IN PATIENTS WITH SUSPECTED CORONARY ARTERY DISEASE
Authors: Martin Hadamitzky, Sebastian T&auml;ubert, Simon Deseive, Stefan Martinoff, Albert Schoemig, J&ouml;rg Hausleiter
Journal: Journal of the American College of Cardiology (2012)
<i>SLC25A32</i> Mutations and Riboflavin-Responsive Exercise Intolerance
Authors: Manuel Schiff, Alice Veauville-Merllié, Chen Hsien Su, Alexander Tzagoloff, Malgorzata Rak, Hélène Ogier de Baulny, Audrey Boutron, Hélène Smedts-Walters, Norma B Romero, Odile Rigal, Pierre Rustin, Christine Vianey-Saban, Cécile Acquaviva-Bourdain
Journal: New England Journal of Medicine (2016)

A patient with late-onset exercise intolerance had haploinsufficiency of SLC25A32, which encodes the human mitochondrial flavin adenine dinucleotide transporter. The patient's symptoms were highly responsive to oral supplementation with riboflavin.
495 RISK FACTORS FOR FIBROSIS PROGRESSION IN ADDICTED PATIENTS WITH CHRONIC HEPATITIS C ON METHADONE MAINTENANCE THERAPY
Authors: M. Simonova, D. Takov, I. Vasilevski, N. Tomov, G. Vasilev, D. Aleksieva, E. Nakov, A. Fakirova, A. Mihova, K. Katzarov
Journal: Journal of Hepatology (2013)
538 A CLINICAL–BIOCHEMICAL–HISTOLOGICAL (CBH) MODEL IMPROVES LONG-TERM MORTALITY PREDICTION IN MALE AND FEMALE PATIENTS WITH ALCOHOLIC LIVER DISEASE
Authors: C. Lackner, W. Spindelboeck, J. Haybaeck, L. Terracciano, J. Matejka, P. Douschan, R. Stauber
Journal: Journal of Hepatology (2013)
RIGHT VENTRICULAR SIZE AND FUNCTION AT PRESENTATION IN PERIPARTUM CARDIOMYOPATHY ARE ASSOCIATED WITH SUBSEQUENT LEFT VENTRICULAR RECOVERY
Authors: Lori Blauwet, Dennis McNamara, Antonia Delgado-Montero, Keiko Ryo, Josef J. Marek, Rami Alharethi, Paul J. Mather, Kalgi Modi, Richard Sheppard, Vinay Thohan, Jessica Pisarcik, John Gorcsan
Journal: Journal of the American College of Cardiology (2015)
Clinical Importance of Myeloid Antigen Expression in Adult Acute Lymphoblastic Leukemia
Authors: Robert E. Sobol, Rosemarie Mick, Ivor Royston, Frederick R. Davey, Rose Ruth Ellison, Roland Newman, Janet Cuttner, James D. Griffin, Heli Collins, Douglas A. Nelson, Clara D. Bloomfield
Journal: New England Journal of Medicine (1987)

To determine the clinical importance of immunophenotypes in adult acute lymphoblastic leukemia (ALL), we prospectively studied 76 patients with this condition. Before treatment, lymphoblasts were tested for reactivity with monoclonal antibodies to B-cell, T-cell, and myeloid (My) antigens. Unexpectedly, myeloid antigens (MCS-2 or MY9) were identified in 25 patients (33 percent), usually in conjunction with B-cell or T-cell antigens. Among My+ patients, 15 (60 percent) expressed B-cell antigens (B+T-y+); all 6 tested had rearranged immunoglobulin genes. Five patients (20 percent) expressed T-cell antigens (B-T+My+), and one My+ patient expressed both B-cell and T-cell antigens. Only myeloid antigens (B-T-My+) were expressed in four patients (16 percent); three who were tested had germ-line immunoglobulin and T-cell–receptor gene configurations. Although no significant differences in presenting clinical features were found, My+ patients had fewer complete remissions than My- patients (35 vs. 76 percent, P<0.01). No differences in response or survival were observed between My+ and My- patients expressing T-cell antigens. However, among those expressing B-cell antigens, My+ patients had fewer complete remissions (29 vs. 71 percent, P = 0.02) and shorter survival (P = 0.03; median, 8.1 vs. >26 months). These findings indicate that expression of myeloid antigen identifies a high-risk group of patients with adult ALL for whom alternative forms of treatment should be investigated. (N Engl J Med 1987; 316:1111–7.)
Hemoperitoneum caused by hemorrhage of tubal vessels, a previously undescribed complication of colonoscopy
Authors: N. Alcaide, R. Atienza, J. Barrio, C. de la Cuesta, M. Pérez-Miranda
Journal: Endoscopy (2011)

A 46-year-old woman underwent colonoscopy due to iron-deficiency anemia. The patient had previously undergone an operation for ovarian endometriomas. During this procedure, when the operator was advancing with the endoscope to the sigmoid colon, the patient suddenly suffered a severe abdominal pain. The exploration was suspended before perforation was suspected.
Doctors and their faiths
Authors: Ka-Po Chan, Mark Pickering, Sanjay A Pai, Aziz Sheikh, Andrew Solomon
Journal: BMJ (2003)

Buddha Sakayamuni Buddha Sakayamuni is the Buddha of the current era. He was neither god nor prophet. He was born around 500 BC as the son of a small princely family on the southern borders of what is now called Nepal. He was born as a human being but achieved enlightenment aged 35 and then became Buddha. After that time, for the next 45 years, Buddha's life consisted of preaching around the area of the mid-Ganges. He had many followers. Since that time Buddhism has become established in the world. Buddha means the enlightened one, but also has another meaning: the great lord of healing. This means that Buddha's teaching centres on how to deal with human suffering and how to take care of human sorrow so, in effect, he worked in the same way as a doctor. This is the reason why I wanted to be a doctor. I can take care of my patients, not just their physical illness but also their mind and spirit.
Comparison of hemodynamic and inflammatory changes between transoral and transthoracic thoracoscopic surgery
Authors: YH Liu, Y Chu, CY Liu, YC Wu, MJ Hsieh, TP Chen, YK Chao, CY Wu, HC Yuan, PJ Ko, HP Liu
Journal: Endoscopy (2012)

Background: Natural orifice transluminal endoscopy has been developed for abdominal surgical procedures. The aim of this study was to compare the surgical outcome between a novel transoral approach and a standard transthoracic approach for the thoracic cavity in a canine model.
Natural orifice transluminal endoscopic surgery
Authors: T. Hucl, J. Spicak
Journal: Endoscopy (2011)

It is now more than a decade since the first description of the concept of natural orifice transluminal endoscopic surgery (NOTES). The first decade was characterized by a substantial number of experimental studies conducted to develop optimal techniques and overcome various challenges. Reports of clinical NOTES procedures in humans began to appear in 2007 and increased in subsequent years. The gastroenterologist performing early experimental studies in animals has now been largely replaced by a surgeon, operating mainly in a hybrid fashion (with laparoscopic assistance) and often using rigid instruments, sparing the flexible endoscope.
Ligation of the Inferior Vena Cava for the Prevention of Pulmonary Embolism
Authors: Eugene A. Gaston, Hugh Folsom
Journal: New England Journal of Medicine (1945)

THROMBOSIS in the deep veins of the lower extremities has been shown to be a frequent source of postoperative pulmonary emboli. The demonstration by Homans,1 2 3 Frykholm4 and others that such thromboses usually begin in the veins of the foot or lower leg, with later extension into the femoral and iliac veins, has led to enthusiastic attempts to prevent embolic sequelae by venous ligation proximal to the thrombotic process. Because of their easy accessibility and the fact that in early cases they lie above the site of thrombosis, the superficial and common femoral veins have generally been chosen as the sites . . .
CS-20 * TRANSCRIPTIONAL CONTROL OF THE OSMOTIC ENGINE BY TEAD4 POTENTIATES INVASION AND CONFERS POOR PROGNOSIS IN GLIOBLASTOMA
Authors: J. C. Martinez-Gutierrez, S. R. Shah, A. Ruiz-Valls, N. D. Tippens, A. Quinones-Hinojosa
Journal: Neuro-Oncology (2014)

Glioblastomas are characterized by their ability to disseminate into the local brain parenchyma; thus, confounding surgical excision and radiotherapy. Hence, it is imperative to identify and decipher the signaling networks that drive invasion. Glioblastoma cells utilize molecular transporters at both their leading (inward facing) and lagging (outward facing) edge to modulate cell volume and invade the confined microenvironment of the brain. These transporters include solute transporters as well as the aquaporins, and collectively behave as an osmotic engine for cellular invasion. However, the transcriptional regulators of these transporters have not been fully identified. Here, we report that TEAD4, a transcription factor implicated in neural development, is a potent regulator of the osmotic engine through transcriptional control of solute and water transporters. In particular, our data demonstrates that loss of TEAD4 decreases glioblastoma cells ability to migrate and invade through small pores (Boyden chamber and Matrigel transwell, respectively) mimicking the confined microenvironment of the brain (p < 0.05). Additionally, we uncover the role of TEAD4 in regulating members of the Na + /H+ exchanger, chloride co-transporter and aquaporin families, as well as the volume regulated anion channel to enable water permeation (p < 0.05). Apart from regulating cell dispersal, our data also shows that TEAD4 regulates glioblastoma proliferation (p < 0.05). Using the TCGA and REMBRANDT datasets, we observed TEAD4 is selectively overexpressed and hyperactive in glioblastomas compared to non-cancer cortex and lower grade gliomas (p < 0.05). Furthermore, we found that patients with elevated TEAD4 expression have a significantly shorter progression free survival and overall survival (p < 0.05). Taken together, our results show that TEAD4 is a potent regulator of cell dispersal through transcriptional control of the osmotic engine and has relevance to clinical outcomes of glioblastoma patients. Hence, TEAD4 may be a selective and potent therapeutic target that warrants further exploration.
Abstract 5210: Over-expression of cancer stem cell markers predicted poor prognosis in colorectal cancer
Authors: Mayumi Ozawa, Yasushi Ichikawa, Takashi Oshima, Akihisa Kondo, Kenichi Nakazawa, Hidetoshi Miyata, Yunwen Zheng, Manabu Shimozawa, Makoto Akaike, Hirokazu Suwa, Kenji Tatsumi, Kazuteru Watanabe, Mitsuyoshi Ota, Shoichi Fujii, Itaru Endo, Hideki Taniguchi
Journal: Cancer Research (2011)

Abstract Introduction: Previous reports have demonstrated that CD133+CD44+ cells might be putative colorectal cancer stem cells (CSCs). Intestinal stem cell marker is already identified as LGR5 in mice, and it is also reportedly in human. However the correlation of CSCs and normal stem cell are unclear. The stem-cell-specific loss of APC (adenomatous polyposis coli) results in progressively growing neoplasia. Therefore, LGR5 may play a crucial role in the carcinogenesis and tumorigenesis. In this study, we investigated the possibility of LGR5 as shared common markers by CSCs and normal stem cells, furthermore to address the correlation among LGR5, CD44 and CD133. Material and Methods: We used surgical specimens of cancer tissue to digest it into single cell suspension. The cells were immuno-stained for flow cytometory, the antigenic profiles of CD133 and CD44 were analyzed. Furthermore, the fractionated cells were sorted and transplanted into NOD/SCID mice. The xenograft tumors were analyzed by flow cytometory again or quantitative real-time PCR (qRT-PCR). And more, total RNA isolated from colorectal cancer and adjacent normal mucosa in 202 patients with untreated colorectal cancer was prepared and complementary DNA (cDNA) was synthesized from total RNA. qRT-PCR was performed to observe the expressions of LGR5, CD44 and CD133. Results: In vivo subcutaneous transplantation showed that as few as 100 CD133+CD44+ cells from primary tumor tissue had tumorigenicity in NOD/SCID mice, where in this cell fraction LGR5 was higher positive compared with other fractions. In xenograft, proportion of LGR5, CD133 and CD44 were expanded as compared with primary cancer and adjacent normal mucosa. In 202 clinical specimens, LGR5, CD44 or CD133 was expressed strongly compared with normal mucosa (p&amp;lt;0.0001). However, with any single marker was not enough to predict the prognosis. Instead, combined with CD44 or CD133, the group of LGR5 over-expression showed significantly low survival rate (p&amp;lt;0.022). Conclusion: LGR5+, CD133+ or CD44+ cells expressed the characters of cancer stem cells in xenograft tumors as well as in primary colorectal cancers. Importantly, LGR5 is a potentially critical factor determining prognosis in clinics. 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 5210. doi:10.1158/1538-7445.AM2011-5210
Association of Anergy with an Immunosuppressive Peptide Fraction in the Serum of Patients with Cancer
Authors: Arthur H. Glasgow, Richard B. Nimberg, James O. Menzoian, Inna Saporoschetz, Sidney R. Cooperband, Karl Schmid, John A. Mannick
Journal: New England Journal of Medicine (1974)

To study the relation between circulating immunosuppressive factors and anergy in patients with cancer, we tested 53 patients with cancer for hypersensitivity to skin-test antigens and 2,4-dinitrochlorobenzene. Of 41 patients with negative skin tests, 27 (66 per cent) had immunosuppressive serum (≥70 per cent inhibition of lymphocyte stimulation by phytohemagglutinin). None of 12 with positive skin tests had immunosuppressive serum. Thus, anergy and serum immunosuppressive activity were correlated (p<0.05). After ion-exchange chromatography, most of the immunosuppressive activity in cancer serum was in the first peak, fraction I. The same fraction from subjects without cancer contained no detectable immunosuppressive activity. Mean total immunosuppressive activity of cancer serum was 166.0 ± 97.5 (S.D.) units, and that of non-cancer serum was 30.4 ± 9.2 units (p<0.05). Diafiltration of fraction I. from cancer serum yielded a fraction (< 10,000 daltons) that was highly immunosuppressive. Thus, anergy in cancer appears correlated with the presence of a circulating immunosuppressive serum component. (N Engl J Med 291: 1263–1267, 1974)
Abstract LB-295: Combination of PI3K (SAR245408 and SAR245409) and MEK (MSC1936369B) inhibitors induce tumor apoptosis in vivo: fluorescence molecular tomography study in a human colon carcinoma xenograft model
Authors: Stephane GUERIF, Sebastien D'heilly, Celine Lefranc, Coumaran Egile, Laurent Debusshe, Loïc Vincent, Chantal Carrez, Marielle Chiron, Jiango Ma, Janet A. Ogden, Joanne Lager, Carlos Garcia-Echeverria, Christoph Lengauer
Journal: Cancer Research (2011)

Abstract The Merck-Serono MEK1/2 allosteric inhibitor MSC1936369B (formerly known as AS703026) was combined with the sanofi-aventis pan-PI3K inhibitor SAR245408 (also known as XL147) or the pan-PI3K/mTOR inhibitor SAR24540 (also know as XL765) in mice bearing colon carcinoma HCT116 xenograft tumors. These tumors harbor both KRAS (G13D) and PIK3CA (H1047R) mutations. Apoptosis induction was monitored non-invasively in vivo using fluorescence molecular tomography (FMT) after injection of fluorescent Annexin-V. Ex vivo apoptosis was assessed on tumor lysates using assays for cleaved caspase-3 and cleaved PARP detection. Suboptimal doses of SAR245408, SAR245409, and MSC1936369B were administered orally on a daily schedule as single agents or in combination. Single agent treatments showed marginal or no activity on HCT116 tumor growth inhibition. In contrast, robust enhanced anti-tumor activity was observed with the combination treatments, resulting in sustained tumor stasis and regression for both SAR245408/MSC1936369B (p&amp;lt;0.0001) and SAR245409/MSC1936369B (p=0.0009) combination regimens. This therapeutic synergy was associated with clear induction of tumor apoptosis after four days of treatment, as evidenced by markedly increased levels of cleaved caspase-3 and cleaved PARP proteins in the tumor lysates. Apoptosis monitored in vivo by FMT was induced for the SAR245408/MSC1936369B combination, with p=0.005 and p&amp;lt;0.0001 after three and seven days of therapy respectively. In conclusion, the combination between the MEK1/2 inhibitor MSC1936369B with the pan-PI3K inhibitor SAR245408 or the pan-PI3K/mTOR SAR245409 resulted in significantly enhanced anti-tumor activity in a KRAS/PIK3CA mutated tumor xenograft model, with synergistic induction of tumor apoptosis as demonstrated ex vivo for both combinations and in vivo using longitudinal FMT imaging for the SAR245408/MSC1936369B combination. 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 LB-295. doi:10.1158/1538-7445.AM2011-LB-295
Abstract 137: MicroRNA-200c restores anoikis sensitivity in breast and gynecological cancers
Authors: Jennifer K. Richer, Erin N. Howe, Dawn R. Cochrane
Journal: Cancer Research (2011)

Abstract Background: MicroRNA-200c directly targets ZEB1, an epithelial to mesenchymal (EMT)-inducing transcriptional repressor of E-cadherin and other key determinates of epithelial identity and polarity. Therefore, restoration of miR-200c results in repression of ZEB1, dramatic reduction in migration and invasion, and increased sensitivity to microtubule targeting chemotherapeutics. We hypothesized that in addition to ZEB1, miR-200c targets additional genes that contribute to its myriad effects on maintaining the epithelial phenotype by repressing mesenchymal genes. Results: We performed microarray analysis following restoration of miR-200c to aggressive endometrial cancer cells and identified 18 genes that were both significantly repressed and predicted to be direct targets of miR-200c. These genes, including fibronectin 1 (FN1), class III beta-tubulin (TUBB3), neurotrophic tyrosine receptor kinase type 2 (NTRK2 or TrkB), leptin receptor (LEPR), moesin (MSN1) and Rho GTPase activating protein 19 (ARHGAP19), are all typically expressed only in non-epithelial cells, such as fibroblasts or neurons. Utilizing luciferase reporter assays and mutational analysis, we validate each of these genes as direct targets of miR-200c. We also demonstrate that restoration of miR-200c leads to a dramatic decrease in mRNA and protein levels of these targets. Further we find that restoration of miR-200c restores anoikis sensitivity to suspended cells, leading to over a 1.5 fold increase in cell death. TrkB is a potent suppressor of anoikis in breast and ovarian cancer models. Addition of TrkB lacking the miR-200c binding site reversed the ability of miR-200c to suppress anoikis. Interestingly, neurotrophin 3 (NTF3), a ligand for TrkB, contains 2 putative miR-200c binding sites and is down regulated upon restoration of miR-200c. Thus, loss of miR-200c in carcinoma cells allows inappropriate translation of both TrkB and NTF3, setting up an autocrine loop that results in anoikis resistance. Conclusions: Our data demonstrate that miR-200c serves as a “guardian of the epithelial phenotype” and suppressor of EMT by directly targeting and repressing a program of genes that should not be on in differentiated epithelial cells. We identify a novel function of miR-200c, the ability to suppress anoikis resistance, an important yet understudied step in the metastatic cascade. Funding source: DOD Breast Cancer Program Idea Award BC084162 to JKR 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 137. doi:10.1158/1538-7445.AM2011-137