tbuckley/cabot-search huggingface dataset:
One Single-Time-Point Kidney Uptake From OctreoScan Correlates With Number of Desintegrations Measured Over 72 Hours and Calculated for the 6.7 Hours Half-Life Nuclide 177Lu
Authors: Matthias Miederer, Helmut Reber, Andreas Helisch, Christian Fottner, Matthias Weber, Mathias Schreckenberger
Journal: Clinical Nuclear Medicine (2012)

In somatostatin receptor-targeted therapy, renal toxicity is an expected side effect, and therefore pretherapeutic dosimetry based on a measured kinetics is preferable. In contrast, a convenient one single-time-point scan might also reveal relevant information on expected dose to organs. However, very early time points might not reflect the true retention by the renal cortex and therefore be of limited value to predict dose for the long-lived 177Lu.Dosimetry with 111In-octreotide was performed in 24 patients, and the number of disintegrations (ND) were calculated for 177Lu. Uptake values for each time point were correlated with ND.The fitting algorithm was best with biexponential equations in 18 patients. Mean biologic half-life of the alpha component was 6 hours (+/-12 hours) and for the beta component 82 hours (+/-38 hours). For the early time points, correlation with ND was generally poor. For later time points, correlation increased markedly after 4 hours (4 hours: r = 0.83, 72 hours: r = 0.93) and were also capable of predicting dosimetry to some extent.In conclusion, thorough quantification of the 4 hours single-time-point scans seems to be enough to predict the expected renal dose for radionuclide therapies to some degree.
Abstract PD05-03: What is the appropriate sample (s) on which to perform sequencing for mutational analysis to guide the selection of targeted therapy?
Authors: RK Alpaugh, C Bingham, P Fittipaldi, M Banzi, G Palmer, M Cristofanilli
Journal: Cancer Research (2012)

Abstract BACKGROUND: Success of targeted therapy requires expression of the protein. Tumor tissue source can include diagnostic biopsy, surgical samples from initial or follow-up surgeries, fluids e.g. pleural or ascites and circulating tumor cells (CTC). The goal of using CTCs was 1. To determine whether CTC can be used as a “liquid” tumor biopsy and enable gene sequence information at the single cell level and 2. To determine the heterogeneity represented in the circulation compared to that seen in solid tumor by examining single cells (or a small cluster of cells) for the presence of a specific mutation which was detected in tissue tumor source. METHODS: We performed sequencing for mutational analysis on tissue(s) from patients with inflammatory breast cancer (IBC). Tumor sources varied from mastectomy tissue, metastatic site(s) e.g. liver or skin from chest wall disease, pleural fluid and CTC isolated into pure single cell populations (or groups of cells) using Silicon Biosystems DEPArray. Ampli1™ WGA kit was used for CTC amplification. Of the 22 patients sequenced, mastectomy primary tumor was examined in 3, metastatic site skin chest wall disease in 15, other metastatic site in 4, pleural fluid in 2 and CTC collected to investigate p53 mutations in 8. RESULTS: To date 22 patients have had mutational data performed, 14/22 had mutations in p53, 4/22 in RB1, 2/22 in each PI3K and ERBB2, 1/22 in each of BRAC1, BRAC2, ATM, KRAS, Notch 1, MEN1 and ESR1. Numerous amplifications were noted including AKT1, RPTOR, MLC1, MYC, CCND1 and ERBB2. For one patient's chest wall biopsy compared to two single CTCs and a cluster of 10 CTCs the same TP53C229fs*10 mutation was detected revealing the same 2bp deletion. No 2bp deletion was found in single white blood cells. Whereas, another patient which showed a TP53 S215G mutation in her skin biopsy of chest wall disease, only amplifications of AURKA, CCND1, IGF1R, MDM2 and SRC in pleural tumor cells were detected and no mutations in three single CTC, two single pleural tumor cells and in single white blood cells were seen. Primary tumor tissue is being sort for both of these patients. Mutational data reviewed to date suggest that IBC is not one disease but a multiplicity of diseases, revealing a variety of target(s). Aberrations are not consistent across tissue source. CONCLUSIONS: Successful treatment outcomes using standard of care chemotherapy combined with target therapies will require not one, but a panel, of tissue sources for sequencing to guide the selection of appropriate targeted therapies. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr PD05-03.
Abstract LB-144: A p53-dependent G2/M checkpoint governed by the cell-fate factor dachshund in non-small cell lung cancer
Authors: Ke Chen, Kongming Wu, Wei Zhang, Jie Zhou, Timothy Stanek, Zhiping Li, Chenguang Wang, L. Andrew Shirley, Hallgeir Rui, Steven Mcmahon, Richard G. Pestell
Journal: Cancer Research (2012)

Abstract Lung cancer is the leading cause of cancer mortality worldwide with more than 170,000 cases diagnosed each year in the United States. Genetic studies have identified several oncogenes activated in lung cancer including K-Ras and EGFR. Tumor suppressor inactivation occurs including p53 in which LOH is observed in - 60% and mutations arise in 50%. Initially cloned as a dominant inhibitor of the hyperactive EGFR, Ellipse in Drosophila, the mammalian DACH1 gene regulates gene expression of target genes in part through interacting with DNA-binding transcription factors and in part through intrinsic DNA-sequence specific binding properties. Clinical studies have demonstrated a reduced expression of the DACH1 in breast, prostate and endometrial cancer. Given the importance of the EGFR in human lung cancer, we examined the role of DACH1 in lung cancer cellular growth, migration and DNA damage response. Herein, endogenous DACH1 was reduced in human non-small cell lung cancer (NSCLS). Expression levels of DACH1 correlated inversely with clinical stage and pathological grade. Re-expression of DACH1 reduced lung cancer cell colony formation and cellular migration. Cell cycle analyses demonstrated G2/M block by ectopic expression of DACH1 occurs synergistically with p53. DACH1 band p53, requiring p53 R248 and R273, residues commonly mutated in lung cancer. Fluorescent microscopy demonstrated co-localization of DACH1 with p53. Immunoprecipitation and western blot assay showed DACH1 association with p53 required the C-terminus of DACH1. DACH1 enhanced p53 transcriptional induction of p21 promoter, p53 and DACH1 repressed Rad51 expression. DACH1 enhanced the cytotoxcity of cisplatin and doxorubicin, two commonly used drugs for NSCLS. Together, our studies demonstrate that p53 is DACH1 binding partner that inhibits NSCLS cellular proliferation. 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-144. doi:1538-7445.AM2012-LB-144
Endoscopic Ultrasound-Guided Celiac Plexus Block (EUS-CPB) and Neurolysis (EUS-CPN): Evaluation of Complications: A Prospective Single Center
Authors: V Shami, A Hernandez, P Yeaton, M Kahaleh
Journal: Endoscopy (2006)

Introduction: EUS-CPB and CPN have been increasingly used for pain control in patients with chronic pancreatitis and unresectable pancreatic cancer. Significant reported complications include hemoperitoneum, perforation, abscess and sepsis. We have prospectively evaluated our complications using this technique.
What is the most reliable imaging modality for small colonic polyp characterization? Study of white-light, autofluorescence, and narrow-band imaging
Authors: A. Ignjatovic, J. East, T. Guenther, J. Hoare, J. Morris, K. Ragunath, A. Shonde, J. Simmons, N. Suzuki, S. Thomas-Gibson, B. Saunders
Journal: Endoscopy (2011)

In vivo optical diagnosis of small colorectal polyps has potential clinical and cost advantages, but requires accuracy and high interobserver agreement for clinically acceptability. We aimed to assess interobserver variability and diagnostic performance of endoscopic imaging modalities in characterizing small colonic polyps.High quality still images of 80 polyps < 1 cm were recorded using white-light endoscopy (WLE), autofluorescence imaging (AFI) and narrow-band imaging with and without magnification (NBI and NBImag). All images were assessed for quality, prediction of polyp histology, and vascular pattern intensity (with NBI) by nine experienced colonoscopists (four experts in advanced imaging) from five UK centers. Interobserver agreement (kappa statistic), sensitivity, specificity, and accuracy were calculated compared with histopathological findings.Interobserver agreement for predicting polyp histology using NBImag was significantly better for experts (κ = 0.63, substantial) compared with nonexperts (κ = 0.30, fair; P < 0.001), and was moderate for all colonoscopists with WLE, AFI and NBI. Interobserver agreement for vascular pattern intensity using NBI was 0.69 (substantial) for experts and 0.57 (good) for nonexperts. NBImag had higher sensitivity than WLE (experts, 0.93 vs. 0.68, P < 0.001; nonexperts, 0.90 vs. 0.52, P < 0.001) and higher overall accuracy (experts, 0.76 vs. 0.64, P = 0.003; nonexperts 0.61 vs. 0.40, P < 0.001). AFI had worse accuracy than WLE for both expert colonoscopists (0.53 vs. 0.64, P = 0.02) and nonexperts (0.32 vs. 0.40, P = 0.04).Of the imaging modalities tested, NBImag appeared to have the best overall accuracy and interobserver agreement, although not adequate for in vivo diagnosis. NBI and AFI did not have better sensitivity, specificity, or accuracy compared with WLE.
Abstract 1475: Role of FcγRIIB in metastatic melanoma and rhabdomyosarcoma
Authors: Andrew J. Lu, Yanlin Yu, Glenn Merlino
Journal: Cancer Research (2011)

Abstract FcγRIIB, known as immunoglobulin gamma Fc region receptor II-b, is a low affinity surface receptor protein for IgG in hematopoietic cells. As an inhibitory receptor, FcγRIIB contains an immunoreceptor tyrosine-based inhibition motif (ITIM) in their cytoplasmic tails that transduces an inhibitory signal on coligation with the activating receptors. FcγRIIIb is anchored to the plasma membrane via a C-terminus-linked GPI moiety. Present exclusively on human neutrophils, it plays a predominant role in binding of immune complexes. Its co-aggregation with FcγRIIa activates phagocytosis, degranulation, and the respiratory burst leading to destruction of opsonized pathogens. Activation of neutrophils leads to secretion of a proteolytically cleaved soluble form of the receptor corresponding to its two extracellular domains. Soluble Fc RIIIb exerts regulatory functions by competitive inhibition of Fcγ R-dependent effector functions and via binding to the complement receptor CR3. Dysregulation of FcγRIIB can promote the susceptibility and severity of several organ-specific and systemic autoimmune diseases invivo. Studies have recently shown that FcγRIIb increased constitutively in malignant lymphocytes and upregulated ectopically melanoma. Using cDNA microarray analysis, we have found that FcγRIIb is upregulated in metastatic melanoma and rhabdomyosarcoma (RMS). These results suggest that FcγRIIb maybe involved in regulation of progression to metastatic state in tumor.To study the role of FcγRIIb in metastatic diseases; we established model systems which stably express wild-type and mutants FcγRIIb in melanoma B16 and RMS772 cells. Cell colonies stably expressing FcγRIIb were selected and tested in vitro and in vivo. Our data showed that expression of FcγRIIb inhibited cell proliferation and caused a noticeable change in cell morphology, but did not affect cell motility and invasiveness. However, overexpression of FcγRIIb significantly stimulated lung metastasis of both melanoma and RMS cell lines. Our data suggest that over-expression of FcγRIIb promotes metastasis in melanoma. 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 1475. doi:10.1158/1538-7445.AM2011-1475
Chronology and Pattern of Human Chromosome Replication. II. Autoradiographic Behavior of Various Y and X Chromosomes&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Y. Kikuchi, Avery A. Sandberg
Journal: JNCI Journal of the National Cancer Institute (1965)

Autoradiographic techniques were used for the study of the deoxyribonucleic acid (DNA) replication pattern of sex chromosomes in normal and abnormal human cells. In normal male cells the Y was the last chromosome to replicate its DNA, the grain content being 4 to 5 times that of the G-group chromosomes, with which the Y chromosome may be confused. In subjects with 2 Y chromosomes, 1 replicated early and the other very Iqte. The autoradiographic behavior of a long Y in a subject with acute leukemia was similar to that of the normal Y. Analysis of the length and arm ratio of the X chromosome revealed it to be similar in length to autosome C8 and not C6, as has been generally held. These studies may serve as a possible model for a more rigorous morphologic definition of the various chromosomes and may explain the asynchronous DNA replication of chromosomes when more than one of a type is present in a cell.
A man with a short history of lower back pain
Authors: Alison Edwards, Preethi Nalla, L D Premawardhana
Journal: BMJ (2016)

A previously fit and well 69 year old man presented to his general practitioner with a four week history of lower back pain. He had no history of trauma, took no regular drugs, was an ex-smoker, and did not drink alcohol. Physiotherapy, sought privately, had provided no benefit. His GP prescribed painkillers and reviewed him two weeks later, at which point, with no improvement in symptoms, spinal radiography was organised. Radiography showed multiple compression fractures of vertebrae T11-L2 (fig 1⇓; arrows).



Fig 1  Plain radiograph showing multiple compression fractures of vertebrae T11-L2 (arrows)



The GP arranged blood tests and referred the patient to hospital for assessment. On further questioning, he had recently lost weight and had loss of appetite. Pallor was noted on examination. There were no neurological findings (in particular, no signs of spinal cord compression) and other systems examinations were normal. Rectal examination showed a smooth, enlarged prostate, with normal anal tone and sensation.

Blood tests showed normocytic anaemia (haemoglobin 99 g/L (reference range 130-180), mean cell volume 95 fL (80-100)), and normal white cell and platelet counts. A renal profile was normal, bone profile showed protein 86 g/L (60-80), albumin 35 g/L (35-50), globulin 51 g/L (22-43), alkaline phosphatase 163 U/L (30-130), adjusted calcium 2.74 mmol/L (2.20-2.60), and phosphate 1.64 mmol/L (0.80-1.50). Imaging studies comprised whole spine magnetic resonance imaging (MRI); computed tomography of the thorax, abdomen, and pelvis; and a skeletal survey (fig 2⇓).



Fig 2  Skull radiograph (with contrast) done as part of skeletal survey



1.  What is the diagnosis?

2.  What additional investigations would aid diagnosis?

3.  What complications may arise?

4.  How should this patient be managed?

### 1. What is the diagnosis?

#### Short answer

Multiple myeloma.

#### Discussion

The spinal radiograph shows pathological fractures of T11-L2 (fig 1⇑), suggestive of metastatic disease (for example, from primary kidney, thyroid, or gastrointestinal cancer) …
Abstract PL02-03: Genomic mapping of cancer origins
Authors: Richard J. Gilbertson
Journal: Cancer Research (2012)

Abstract Cancer comprises a bewildering assortment of diseases that kill 7.5 million people each year. Poor understanding of cancer's diversity currently thwarts our goal of a cure for every patient, but recent integration of genomic and stem cell technologies promises a route through this impasse. In particular these studies have provided new insight into the origin of cancer subgroups currently regarded and treated as single diseases. The improved understanding of tumor biology and accurate preclinical models derived from these studies hold promise to advance cures for all patients with cancer. 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 PL02-03. doi:1538-7445.AM2012-PL02-03
Abstract 2097: Targeting aneuploidy with NMS-P153, a tight binder inhibitor of the spindle assembly checkpoint MPS1 (TTK) kinase.
Authors: Riccardo Colombo, Marina Caldarelli, Maria Laura Giorgini, Anna Degrassi, Marina Ciomei, Daniele Pezzetta, Dario Ballinari, Alessia Montagnoli, Enrico Pesenti, Daniele Donati, Arturo Galvani
Journal: Cancer Research (2013)

Abstract Aneuploidy is one of the major hallmarks of cancer and is a unique property of tumoral cells. Targeting of the molecular mechanisms required for growth of aneuploid cells is a potential strategy for developing new therapies with preferential activity against cancer. The Spindle Assembly Checkpoint (SAC) is a mitotic mechanism required for proper chromosomal segregation, ensuring that cells do not divide until all sister chromatids correctly align to the metaphase plate. The SAC is a complex machinery regulated by a number of members which are rarely mutated in tumors. Rather, checkpoint components have been found to be upregulated in aneuploid tumor cells, suggesting a potential tumor “addiction” to SAC functions. MPS1 kinase, (also known as TTK) is an essential enzyme of the SAC complex which is aberrantly overexpressed in a wide range of tumors and necessary for tumor cell proliferation. We previously reported the identification of NMS-P715, a selective and orally bioavailable MPS1 inhibitor, capable of promoting mitotic acceleration, thereby causing massive aneuploidy and cancer cell death both in vitro and in vivo and which promotes tumor growth inhibition in preclinical cancer models. Supported by these results, a lead optimization program was then undertaken which led to the identification of NMS-P153, an optimized product candidate for clinical development. NMS-P153 is selective, shows high in vitro enzymatic potency on MPS1 (IC50 of 3 nM) and a prolonged residence binding time. More than 100 cell lines have been analyzed against NMS-P153 in proliferation studies and several distinct xenograft models have been tested in vivo, allowing the identification of potential genetic contexts of sensitivity. Potent anti-proliferative activity, good tumor growth inhibition associated with tumor regression and biomarker modulation was observed in sensitive xenograft models. A favorable ADME profile, associated with permissive therapeutic safety margins observed in different species at efficacious exposures, indicate that NMS-P153 is suitable for further development, with the potential for being a first-in-class drug targeting MPS1 kinase. Citation Format: Riccardo Colombo, Marina Caldarelli, Maria Laura Giorgini, Anna Degrassi, Marina Ciomei, Daniele Pezzetta, Dario Ballinari, Alessia Montagnoli, Enrico Pesenti, Daniele Donati, Arturo Galvani. Targeting aneuploidy with NMS-P153, a tight binder inhibitor of the spindle assembly checkpoint MPS1 (TTK) kinase. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2097. doi:10.1158/1538-7445.AM2013-2097
Abstract 1397: The effects of mevalonate pathway inhibitors on the motility and invasion of aggressive breast cancers
Authors: Elizabeth J. Kennedy, Eric A. Bracken, Lauren D. Van Wassenhove, LiWei Bao, ZhiFen Wu, Sofia D. Merajver
Journal: Cancer Research (2011)

Abstract The mevalonate pathway is a metabolic pathway responsible for synthesizing prenyl (both farnesyl and geranylgeranyl) groups and activating small GTPase proteins through transfer of these groups by covalent modification. These GTPase proteins include RhoA, RhoC, Rac and Cdc42, which regulate the actin cytoskeleton during cellular migration and are over-expressed in many cancers. This project explores the effects of three mevalonate pathway inhibitors–zoledronic acid, atorvastatin and geranylgeranyl transferase inhibitor (GGTI)–on the single-cell motility, collective cell migration and invasion of an aggressive breast cancer line (MDA-MB-231) and an inflammatory breast cancer derived (IBC) line (SUM149). We are using MCF10A immortalized breast cells as our “normal-like” control. We hypothesize that these cancers rely on this pathway for cellular motility, invasion and the structure of the actin cytoskeleton more than normal epithelial cells. We observed significant decreases in total quantities of Rac, RhoC and Cdc42 and a striking increase in RhoA upon treatment with each separate inhibitor, observed by western blot. The effect is much more potent with atorvastatin and GGTI, resulting in an almost complete loss of lamellipodia and filopodia. We assayed for invasion through 3D culture transwell chambers, individual cell motility using a bead motility assay and live-cell imaging, and collective cell migration using a wound healing assay. In general, all three drugs were highly effective at inhibiting both types of cell migration and invasion in MDA-MB-231 cells. While all drugs inhibited the collective cell migration of SUM149 cells, only GGTI additionally inhibited invasion and single cell migration. This result suggests that an approach targeting geranylgeranylation may be more effective for inhibition of IBC cells. Typically IBC tumors use collective cell migration mechanisms to metastasize, whereas MDA-MB-231 tumors metastasize through single-cell migration. Our results show that aggressive breast cancers heavily rely on the mevalonate pathway for cellular motility in comparison to normal epithelial cells, and that inhibitors of this pathway have significant potential to inhibit the metastatic properties of these two tumor types, given their mechanism of tissue invasion. We are continuing to study collective cell movement by assaying for cell-cell adhesion molecules upon treatment with our three inhibitors. In addition, we are studying the effects of these inhibitors on metastasis in vivo using xenograft mouse models and Her2Neu transgenic mouse models. 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 1397. doi:10.1158/1538-7445.AM2011-1397
REAL-WORLD PRACTICE PATTERNS OF DOFETILIDE AND SOTALOL UTILIZATION FOR ATRIAL FIBRILLATION: A MULTI-NATIONAL SURVEY
Authors: Madhu Reddy, Jayasree Pillarisetti, Sandia Iskandar, Moustapha Atoui, Madhav Lavu, Donita Atkins, Sudharani Bommana, Rhea Pimentel, Loren Berenbom, Raghuveer Dendi, Martin Emert, Dhanunjaya Lakkireddy
Journal: Journal of the American College of Cardiology (2016)
Multiple FDG-Avid Injection Site Granulomas Due to Lovenox Injection
Authors: Bin Liu, Sherwin Chan, Sabah Servaes, Hongming Zhuang
Journal: Clinical Nuclear Medicine (2014)

An initial staging FDG PET/CT scan in a 15-year-old female patient with lymphoma revealed FDG-avid tumor in the mediastinum and the neck. After chemotherapy, a restaging PET/CT scan was performed. Although mediastinal and cervical lesions were not visualized, multiple new foci of activity were noted in the bilateral anterior thighs, which corresponded to soft tissue nodules in the subcutaneous tissue on the low-dose CT. On the third PET/CT study, multiple new foci appeared in the subcutaneous tissue in the anterior abdomen. Additional clinical history was obtained, indicating multiple recent subcutaneous injections of anticoagulants.