tbuckley/cabot-search huggingface dataset:
Abstract 440: Characterization and comprehensive proteomic analysis of exosomes derived from prostate cancer cell lines
Authors: Elham Hosseini-Beheshti, Steven Pham, Hans Adomat, Emma S. (Tomlinson) Guns
Journal: Cancer Research (2011)

Abstract Background: Exosomes are extracellular nano-vesicles which are secreted upon fusion of multivesicular bodies with the plasma membrane and present in most body fluids. They have been shown to be derived from a multitude of cell types and, while it is postulated that they are important for membrane trafficking as communication vesicles, their relevance in cancer and specifically prostate tumour growth and progression has yet to be determined. Factors such as stage of cancer, cell type and cell cycle could affect the amount and composition of exosomes formed and secreted. While the mechanisms underlying exosome formation and secretion are not fully understood, characterization of exosomes derived from different androgen dependent and independent prostate cancer cell lines (LNCaP, C4-2, VCaP, DU-145, PC-3) versus normal epithelial prostate cell line (RWPE-1) indicate novel information about their possible role in prostate cancer. In Addition proteomic analysis of exosomes derived from different prostate cancer cell lines reflects differential protein content within these entities and could be considered for prognostic potential. Other studies on tumour-related microvesicles suggest the role of these selectively enriched exosomes in cancer progression therefore the presence of differential protein markers in and on prostate cancer cell derived exosomes may yield potential biomarkers for cancer diagnosis and therapeutic response. In this study we characterized exosomes derived from different prostate cancer cells and explain the role of specific proteins present within exosomes which are involved in prostate cancer progression. Methods and Results: Exosomes were purified from the conditioned media(CM) from a panel of five prostate cancer cells and ‘normal’ RWPE-1 cells after 72 hours serum free media treatment. Using differential centrifugation cell debris and protein aggregates were removed from CM. Finally exosomes were isolated in a 30% sucrose cushion using ultracentrifugation. Further analysis using transmission electron microscopy detected the integrity of purified exosomes. Western blot analysis was also used to probe for different exosome markers including Actin, HSP70, HSP90, Rab5, CD9 and CD63. Our proteomic data shows that exosomes derived from specific prostate cancer cells present potential markers of prostate cancer progression. Conclusion: This study highlights a potential for differential protein composition of exosomes as a source of diagnostic biomarkers in addition to therapeutic targets for prostate cancer via non-invasive testing. 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 440. doi:10.1158/1538-7445.AM2011-440
Skin thickness as a measure of breast lymphedema.
Authors: AC Degnim, TL Hoskin, AL Cheville, JP Miller, GL Gamble, LM Baddour, JH Donohue, KM Thomsen, SD Maloney, JC Boughey
Journal: Cancer Research (2009)

Abstract Abstract #3103 Introduction: Lymphedema is well-known in the arm but can also occur in the breast. Diagnosis is currently non-standardized and based on clinical impression. We sought to determine if skin thickness could serve as a useful measure in the diagnosis of breast lymphedema (BLE).&amp;#x2028; Methods: Patients undergoing unilateral non-mastectomy procedures were enrolled on this prospective clinical study preoperatively and evaluated for signs and symptoms of lymphedema in the operated breast in the postoperative period. Patients with established BLE were also studied. BLE diagnosis was independent of ultrasound findings and was based on a graded physical exam targeting clinical signs of edema and erythema. Skin thickness was measured with ultrasound at the 6 o'clock position of both breasts. Differences in skin thickness were assessed by the ratio of skin thickness in the operated and contralateral breasts, with comparison of means by two-sample t-test. Receiver operating characteristic curves were constructed to estimate the area under the curve (AUC) and to determine optimal cutpoints.&amp;#x2028; Results: Ninety-seven women were studied; 85 were enrolled preoperatively and 12 postoperatively after a diagnosis of BLE. Median length of follow-up overall was 8 months. Of the 97 women, 46 had BLE at one or more follow-up visit with median time to first diagnosis of 3 months. Mean measured skin thickness was 2.3 ± 0.5mm in unaffected breasts and 3.2 ± 1.0 mm in operated breasts. Women with BLE had significantly greater skin thickness in the operated breast compared to the contralateral breast, with a mean skin thickness ratio of 1.83 ± 0.57 in patients with BLE compared to 1.18 ± 0.40 among those without BLE (p&amp;lt;0.0001). Skin thickness ratio provided excellent discrimination for BLE, with an area under the curve (AUC) of 0.86. At a ratio of 1.32 or greater (32% greater skin thickness in operated versus contralateral breast), sensitivity and specificity for diagnosing BLE were 81% and 82% respectively. A single measure of skin thickness in the operated breast also correlated well with diagnosis of BLE, with skin thickness of 3.2 mm or greater demonstrating sensitivity of 78% and specificity of 82%, AUC 0.82.&amp;#x2028; Conclusions: Breast lymphedema results in skin edema and increased skin thickness that can be quantified with ultrasound. Measuring breast skin thickness- either as a single reading or as a ratio to the unaffected breast- may be useful in the diagnosis of breast lymphedema. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3103.
Endoscopic management of retained patency capsules
Authors: Shashank Garg, Rohit Anand, Ethan Dubin, Sergey Kantsevoy, Sudhir Dutta
Journal: Endoscopy (2014)

A 58-year-old woman presented to the emergency room with pain at her ileostomy site for the previous 5 – 6 hours. She had had a colonic resection for "ulcerative colitis" 15 years earlier. A computed tomography (CT) scan of the abdomen demonstrated a foreign body in the ileostomy opening with proximal small-bowel obstruction ([Fig. 1]). She had ingested a patency capsule earlier that day before capsule enteroscopy for ongoing work-up of iron deficiency anemia. Ileoscopy showed a stricture in the terminal ileum ([Fig. 2]), which was dilated with 8 – 12-Fr through-the-scope balloons. An intact patency capsule proximal to the stricture was retrieved with a Roth Net retrieval device ( [Fig.3]). Ileitis was noted up to 15 – 20 cm cephalad from the ileostomy opening ([Fig. 4]). Active inflammation with granulation tissue was seen in ileal biopsies suggesting an inflammatory stricture.
Abstract 4125: Suppression of the mevalonate pathway and oncogenic signaling may underlie the tumor-suppressing effects of KLK5 in breast cancer
Authors: Georgios Pampalakis, Osahon Obasuyi, Olga Papadodima, Aristotelis Chatziioannou, Vassileios Zoumpourlis, Georgia Sotiropoulou
Journal: Cancer Research (2012)

Abstract Kallikrein-related peptidase 5 (KLK5) has been implicated in different types of cancer based on its aberrant expression in tumor cell lines and tissue specimens and in vitro data, however, functional association is missing. Here, we confirmed that KLK5 is very frequently down-regulated or inactivated in breast cancers of different subtypes. Reconstitution of KLK5 expression by stable transfection in KLK5-negative MDA-MB-231 cells remarkably reversed their malignant phenotype both in vitro (wound scratch and soft agar assay) and in vivo (orthotopic xenograft growth in SCID mice). We found that in KLK5 transfectants Snail1 and the mesenchymal marker vimentin were highly downregulated, pointing to a potential involvement of KLK5 in mesenchymal-to-epithelial transdifferentiation, however, re-expression of E-cadherin could not be demonstrated. Importantly, it appears that KLK5 may severely affect the overall output of the proteolytic web as it minimized the proteolytic activities of MMP9 and MMP3. Unexpectedly, transcriptomic profiling revealed that reconstitution of KLK5 expression suppresses the mevalonate pathway of cholesterol biosynthesis by highly up-regulating INSIG1 (insulin induced gene 1), a major negative regulator of HMGCR (3-hydroxy-3-methylgluratyl-CoA reductase), while KLK5 may also affect cholesterol uptake, as the LDLR (LDL receptor) and PCSK9 (proprotein convertase subtilisin-like/kexin type 9), the main regulator of LDLR, were both found significantly upregulated in KLK5 transfectants. A functional role of KLK5 in the regulation of the mevalonate pathway and protein-prenylation circuitries was demonstrated by reduced cellular cholesterol and prenylation levels, end products of this pathway. Reduced prenylation was shown by the remarkable reduction in the levels of activated RhoA, which must be subjected to isoprenylation (mainly geranyl-geranylation) for activation. To our knowledge, this is the first demonstration of a protease involved in the crosstalk between metabolic pathways and oncogenic signaling. Moreover, among the genes found up or down-regulated upon KLK5 re-expression (i.e. the “KLK5 signature”) were several genes known to be involved in atherosclerosis and other lipid-related metabolic disorders. Overall, KLK5 may represent a nodal interconnection of proteolytic and signaling pathways in cancer but may also participate in pathways associated with metabolic diseases, in support of the emerging concept of common genetic networks governing both cancer and lipid-associated disorders. 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 4125. doi:1538-7445.AM2012-4125
Spectrum and Classification of <i>ATP7B</i> Variants in a Large Cohort of Chinese Patients with Wilson's Disease Guides Genetic Diagnosis
Authors: Yi Dong, Wang Ni, Wan-Jin Chen, Bo Wan, Gui-Xian Zhao, Zhu-Qing Shi, Yue Zhang, Ning Wang, Long Yu, Jian-Feng Xu, Zhi-Ying Wu
Journal: Theranostics (2016)

Wilson's disease (WD) is an autosomal recessive disorder of copper metabolism caused by ATP7B pathogenic mutations. The symptoms of WD can be effectively prevented if the affected individuals are identified and intervened early. However, clinical utility of this molecular analysis is challenging due to hundreds of variants with various clinical effects in the gene. Here, we aim to describe the spectrum of ATP7B variants and assess their clinical effects in the Han Chinese population.The ATP7B gene was directly sequenced in 632 unrelated WD patients and 503 unrelated healthy individuals. The effects of identified variants were classified according to the American College of Medical Genetics and Genomics (ACMG) standards and guidelines. Different frequency of variants observed in both cases and controls were tested using Chi-square or Fisher's exact tests.We detected 161 non-synonymous variants in these 632 WD patients, 58 of which were novel. Among these variants, 78, 64, 8, 4, and 7 were classified as 'pathogenic variants', 'likely pathogenic variants', 'variants with uncertain significance', 'likely benign variants', and 'benign variants', respectively. Ninety percent (569/632) of these WD patients can be genetically diagnosed with two or more 'pathogenic' or 'likely pathogenic' variants. The 14 most common disease-causing variants were found at least once in 94% (537/569) of genetically diagnosed patients.These data expand the spectrum of ATP7B variants and facilitate effective screening for ATP7B variants for early diagnosis of WD and development of individualized treatment regimens.
An Intraoral Mass Associated With Myelodysplastic Syndrome
Authors: James K. Mangan, Milda Chmieliauskaite, Eric T. Stoopler
Journal: JAMA Oncology (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Abstract 4175: Characterization of hsa-miR-135b in human neuroblastoma cell line SK-N-BE(2).
Authors: Chelsea A. Castillo, Judy C. Chang, Jaclyn Y. Hung
Journal: Cancer Research (2013)

Abstract Background: MicroRNAs (miRs) are an abundant class of small (∼22 nucleotides), non-coding, single-strand RNAs (ncRNA) that negatively regulate gene expression at a post-transcriptional level. miRs are thought to act by inhibiting the translation of messenger RNAs (mRNAs) into protein in addition to promoting mRNA degradation. These regulatory ncRNAs play an important role in the control of many biological processes and their deregulation has been implicated in a variety of pathological conditions, including many cancers. Emerging evidence supports the concept that in many cancer types a pool of cancer cells responsible for cancer maintenance and long-term remission failure exhibit stem-like properties. Using a high throughput miR microfluidic card assay qRT-PCR approach, we identified 26 miRs (23 up-regulated and 3 down regulated) as stem-like associated miRs in six pediatric cancer cell lines, including neuroblastoma cell line SK-N-BE(2). hsa-miR-135b was one of the miRs that was up-regulated. The purpose of this study was to characterize the functional consequences of hsa-miR-135b silencing in the SK-N-BE(2) cell line. Methods: hsa-miR-135b expression was knocked down (KD) using Lipofectamine® transfection reagent and a stable cell line was generated in the presence of puromycin. Cell cycle distribution as well as the effect of inhibition on the ability to form neurospheres (read-out for self-renewal) was determined. To investigate the effect on anchorage-independent growth, the ability of the KD cells to form colonies in soft agar was measured. Cell capacity for invasion was tested using basement membrane matrix invasion culture system. Western blot analysis was performed on the components of the Wnt/****B-catenin signaling pathways. Results: Our results indicated that inhibition of hsa-miR-135b impaired sphere formation (read-out for self renewal) as well as growth of colonies on a semi-solid culture media. No significant difference in cell cycle distribution was observed between control and hsa-miR-135b KD cells. Conclusion: Our findings suggest that in our model system, hsa-miR-135b likely plays a role in the maintenance of cancer stem cells and tumor progression. Therefore, it is a promising therapeutic target in neuroblastoma patients. Citation Format: Chelsea A. Castillo, Judy C. Chang, Jaclyn Y. Hung. Characterization of hsa-miR-135b in human neuroblastoma cell line SK-N-BE(2). [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 4175. doi:10.1158/1538-7445.AM2013-4175
Doctors urge more regulation for herbal treatments
Authors: S. Gottlieb
Journal: BMJ (1998)

People trying to treat their own ailments with poorly tested herbal medicines have become severely ill, according to six separate reports published in the New England Journal of Medicine , prompting calls for greater regulatory scrutiny of these alternative treatments.

Lead poisoning, impotence, and abnormal heart rhythms were among the disorders described as resulting from toxic contaminants or from the presence of potent drugs unwittingly mixed into products that were labelled “all natural,” according to …
Case 24-2009
Authors: John H. Stone, Paul A. Caruso, Vikram Deshpande
Journal: New England Journal of Medicine (2009)

A 26-year-old woman was referred to the rheumatology clinic because of painful neck swelling associated with thirst and weight loss. Physical examination revealed submandibular-gland enlargement on both sides of the neck. Testing for antinuclear antibodies was positive, and the levels of serum complement were low; assays for antibodies to the Ro and La antigens were negative. A diagnostic procedure was performed.
OP0121 The Frequency of Bone Erosion and Oedema in Inflammatory and Degenerative Arthropathies Proximal to the Peri-Entheseal Cruciate Ligament Vascular Channels
Authors: D. Binks, M. Matzelle, D. Bergin, R. Hodgson, E. Gravallese, D. McGonagle, A. Radjenovic
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> We noted in mouse models of inflammatory arthritis (IA) that an early point of entry of inflammation into the marrow space occurs at sites where penetrating vessels entered the bone. The role of penetrating vessels in erosion formation in man has not been explored in IA, nor has the role of vascular channels in bone oedema in osteoarthritis (OA) been explored. <h3>Objectives</h3> The purpose of this work was to investigate the frequency of bone erosion and oedema in inflammatory and degenerative arthropathies in close proximity to the peri-entheseal ACL and PCL vascular channels. <h3>Methods</h3> Normal microanatomy was defined in 21 cadaveric knees using 3T MRI and histology. MRI of 89 patients from the Osteoarthritis Initiative study and 27 patients with inflammatory arthritis were evaluated for erosion and bone oedema at the same locations. Two animal models of inflammatory arthritis were evaluated to ascertain whether the putative peri-entheseal vascular regions influenced the propensity of osteitis and bone erosion. <h3>Results</h3> Data from the two animal models of IA showed inflammation entering the marrow space along the adventitia of blood vessels that penetrate the cortical bone in close proximity to the cruciate ligament insertions. On 3T MRI, a vascular channel adjacent to the ACL tibial insertion was observed in 64% of cadaveric specimens examined. Similarly, a vascular channel adjacent to the PCL was seen in 71% of cases. Bone marrow oedema was observed in the regions corresponding to the location of the vascular channel in 51% of knees for both the anterior and posterior channel. Histological evaluation of 10 cadaveric specimens confirmed the location of the vascular channels along with the presence of associated subclinical microdamage including subchondral bone erosion (80% of cases) and micro-cyst formation (50%). Evaluation of patient MRIs showed the prevalence of oedematous features in the same topographic locations in patients with early OA (41% ACL, 59% PCL) and inflammatory arthritis (44% ACL, 33% PCL), (figure 1 ). <h3>Image/graph</h3> <h3>Conclusions</h3> Our findings show that the vascular channels adjacent to the anterior and posterior cruciate ligament entheses are common locations for erosion formation and damage in both inflammatory and degenerative arthritis. Furthermore, we have found a significant clustering of subclinical microdamage in these regions in normal cadaveric samples. Therefore, we conclude that peri-entheseal vascular channels are likely to present a common pathogenesis focus for both OA and IA. <h3>Disclosure of Interest</h3> None Declared
One step EUS-ERCP may optimize the overall costs in the management of patients with common bile duct stones
Authors: C Fabbri, V Cennamo, F Ferrara, AM Polifemo, S Ghersi, S Macchia, ND 'Imperio
Journal: Endoscopy (2006)

Background and aims: Since 2001 in our endoscopic unit we perform, in patients with suspected common bile duct (CBD) stones, echoendoscopy (EUS) preliminary to endoscopic retrograde cholangio pancreatography (ERCP). From May to October 2005 we can perform in the same session EUS and ERCP.
NT-37 * A PHASE II RANDOMIZED STUDY OF NovoTTF THERAPY VERSUS SUPPORTIVE CARE IN NON-SMALL CELL LUNG CANCER PATIENTS WITH 1-5 BRAIN METASTASES FOLLOWING OPTIMAL STANDARD LOCAL TREATMENT
Authors: U. Weinberg, E. Kirson, O. Farber, Y. Palti
Journal: Neuro-Oncology (2014)

BACKGROUND: NovoTTF Therapy is a non-invasive, anti-mitotic treatment modality, based on low intensity alternating electric fields. During mitosis Tumor Treating Fields (TTFields) interfere with the formation of the mitotic spindle and physically translocate charged organelles. TTFields inhibit proliferation of non-small cell lung cancer (NSCLC) in vitro and in vivo. THE EF-21 CLINICAL TRIAL DESIGN: Patients with 1-5 NSCLC brain metastases (BM) who initially received optimal local treatment to all metastases are randomized in a ratio of 1:1 to either NovoTTF Therapy or supportive care alone arms. Patients are followed-up monthly (brain MRI every 3 months). Patient in the control arm may cross over at time of recurrence in the brain. OBJECTIVES: The current trial is designed to study the safety, tolerability and efficacy of NovoTTF therapy in this patient population. ENDPOINTS: Median time to local and distant progression in the brain (primary), neurocognitive function, quality of life, toxicity, overall survival and overall progression free survival (secondary). MAJOR ELIGIBILITY CRITERIA: Diagnosis of BM from NSCLC with stable systemic cancer, 1-5 BM following optimal local therapy, optimal systemic therapy for NSCLC. TREATMENT: Continuous NovoTTF Therapy at 150 kHz, applied to the brain using the NovoTTF-100A(M) System. The System is a portable medical device delivering alternating electric fields to the brain using 4 Transducer Arrays, which may be covered by a wig or a hat for cosmetic reasons. STATISTICAL CONSIDERATIONS: This is a prospective, randomized (1:1), multicenter study for 60 patients, comparing the hazard of progression in the brain over time between both arms using the Kaplan-Meier method. This trial has 80% power at a two sided alpha of 0.05 to detect a hazard ratio of 0.35 in time to progression in the brain. Randomization is stratified by number of BM (single vs. 2-5) and WHO performance score (0-1 vs. 2).