tbuckley/cabot-search huggingface dataset:
Abstract 4075: Aerosol azacytidine inhibits the orthotopic lung cancer in mice by its demethylation function but not cytotoxic effect
Authors: Xuan Qiu, Roman Perez-Soler, Yiyu Zou
Journal: Cancer Research (2012)

Abstract Introduction: Silencing of key tumor suppressor genes by promoter hypermethylation plays an important role in lung cancer carcinogenesis. Reversing the hypermethylation in the early lung cancer cells adjacent to the airway surface may have a potential to inhibit lung cancer development. This study was to explore the therapeutic potential of aerosol administered demethylating agent azacytidine (Aza) for the treatment of bronchial epithelial premalignancy or lung cancer. Methods: The demethylation and gene reactivation functions of Aza administered by aerosol were detected by qPCR methylation array and western blotting assay in the tumor tissues from the orthotopic human non-small cell lung cancer (NSCLC) xenograft models in nude mice. The therapeutic efficacy and toxicity of the aerosol Aza were also evaluate in the same lung cancer models. An intravenous administered Aza with clinical equivalent dose and schedule was used as a control. Results: The aerosol Aza is an appropriate pharmaceutical inhalation formulation with about 80% of droplets size distributing between 0.1 to 5 micron. This aerodynamic size range ensures the aerosol droplets depositing in the lower airway. In animal studies, aerosol administration of Aza significantly prolonged the survival of nude mice with intratracheally inoculated human NSCLC tumors. The %-increased life span was 5- to 10-fold higher than that of a systemic treatment of Aza at a clinical equivalent dose. The aerosol treatment did not cause any detectable lung toxicity or myelosuppression (systemic toxicity of Aza), since the treatment dose was &amp;gt;100-fold lower than the toxic dose. The lung tumors were resected after the aerosol Aza treatment and the methylation levels of the 24 promoters that drive the lung cancer related tumor suppressor genes (TSG) were detected. We found that aerosol Aza significantly reduced the methylation level in 9 of these 24 promoters. The dementhylating aerosol also resulted in the gene reactivation in the protein level of several tested genes. Conclusions: Aerosol administration of Aza has significant therapeutic advantages over the systemic Aza. It can be given at a non-cytotoxic dose, thus its main therapeutic efficacy is the demethylation function of Aza and the TSG reactivation. In our case, the therapeutic index of aerosol Aza is &amp;gt;800-fold higher than that of IV Aza. The clinical trial of aerosol Aza is worth to be conducted. Acknowledgement: Supported by a NIH (NCI) grant 5R01CA154755-02 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 4075. doi:1538-7445.AM2012-4075
PREFRONTAL LEUCOTOMY
Authors: C. D. CONSTANTINIDES, B. STROUSSOPOULOS
Journal: American Journal of Psychiatry (1954)

Based upon 103 cases of prefrontal leucotomy, our experience shows that the operation should be performed in those cases that have failed to respond to other therapy and have become chronic. In many such cases the results are most satisfactory from the medical as well as from the social point of view. An attempt is made to explain the effect of leucotomy upon various mental disorders based upon conjectures concerning the pathophysiology of the brain.
Immunocytochemical Identification of Azurophilic and Specific Granule Markers in the Giant Granules of Chediak-Higashi Neutrophils
Authors: P. Gregory Rausch, Katherine B. Pryzwansky, John K. Spitznagel
Journal: New England Journal of Medicine (1978)

We used immunofluorescent microscopy to characterize the abnormal granules in neutrophils from five patients with Chediak-Higashi disease. Monospecific antiserums to the azurophilic markers myeloperoxidase, elastase, cathepsin G and lysozyme, and to the specific granule markers lactoferrin and lysozyme, were labeled with fluorescein and rhodamine and were used to demonstrate two antigens in the same cell simultaneously. The abnormal granules in Chediak-Higashi neutrophils contained both azurophilic and specific granule markers. Normalappearing lactoferrin-positive granules were also present, but normal azurophilic granules were not seen. Analysis of bone-marrow samples from two of these patients suggested that the abnormal granules were formed during granulocyte maturation by the progressive aggregation and fusion of normally formed azurophilic and specific granules. These results are consistent with a membrane abnormality or a defect of microtubular function leading to inappropriate granule fusion, and suggest that the granular abnormality is more generalized than previously appreciated. (N Engl J Med 298:693–698, 1978)
Abstract 4304: Developing T-LGL leukemia model for targeted therapy
Authors: Tong Ren, Xin Liu, Thomas P. Loughran, Hua Cheng
Journal: Cancer Research (2011)

Abstract T cell type of large granular lymphocyte (T-LGL) leukemia is a hematological malignancy and the disease course is frequently associated with autoimmune diseases. Many patients with T-LGL leukemia have no response to the currently available immunosuppressive therapies. T-LGL leukemia cells display the CD3+/CD8+/CD57+ surface markers, representing activated cytotoxic T lymphocytes with the TCR rearrangement pattern that implicates their clonal expansion nature. The primary leukemic cells exhibit constitutive activities of STAT3 and NF-κB, and both factors are critical mediators of oncogenic signaling and survival pathways. Activated STAT3 contributes to chemotherapy resistance as the repression of STAT3 in LGL leukemic cells down-regulates a survival protein Mcl-1, resulting in an increased sensitivity to apoptosis. Thus, STAT3 activation plays an essential role in promoting aberrant proliferation of the leukemic cells. In addition, NF-κB is activated in LGL leukemia, which also plays a crucial role in survival and proliferation of the leukemia cells. It is of paramount significance to further verify therapeutic agents that target STAT3 and NF-κB for treatment of T-LGL leukemia in a well-defined leukemia model. Extensive efforts, however, failed to establish in vitro culture of primary T-LGL leukemia cells for extended time, because T-LGL leukemia cells are terminally differentiated cytotoxic T lymphocytes and undergo rapid replicative senescence. Lack of T-LGL leukemia model apparently prevents further understanding of the disease pathogenesis and development of targeted therapy. We have developed a strategy that can prolong in vitro culture of T-LGL leukemia cells. Primary CD8+ populations from T-LGL leukemia patients are stably transduced with the retroviral tax gene derived from human T cell leukemia virus type 2. Expression of Tax overrides replication senescence and promotes unlimited expansion of the CD8+ T cells. These cells exhibit features characteristic to T-LGL leukemia, such as resistance to FasL-mediated apoptosis, sensitivity to inhibitors for sphingolipid kinase, IκB kinases and Stat3 as well as expression of cytotoxic gene products including granzyme B, perforin and IFNγ. Collectively, these results indicate that the immortalized CD8+ species from T-LGL leukemia patients constitutes a significant portion of T-LGL leukemic cells, and this leukemia model can duplicate main phenotypes of clinical isolates of T-LGL leukemia. The establishment of the T-LGL leukemia model is tremendously useful for investigating molecular pathogenesis of the disease and for testing novel therapeutics. 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 4304. doi:10.1158/1538-7445.AM2011-4304
Gastric outlet obstruction secondary to percutaneous endoscopic gastrostomy tube placement
Authors: M. Than, J. Witherspoon, G. Tudor, A. Saklani
Journal: Endoscopy (2012)

We report a complication of percutaneous endoscopic gastrostomy (PEG) insertion in a 60-year-old woman with an end-stage neurodegenerative disorder. The first attempt at PEG tube insertion was abandoned due to failure to transilluminate the stomach because of a large hiatus hernia, but a second attempt using a combined fluoroscopic and endoscopic approach was successful. Gastrostomy feeding was commenced 24 hours later following satisfactory postprocedural monitoring. At 48 hours, our patient developed generalized abdominal pain associated with vomiting and fever. Clinical diagnoses of gastrostomy site leakage, gastroparesis, and aspiration pneumonia were made. Subsequent computed tomography (CT) of the abdomen demonstrated the gastrostomy tube traversing the left anterior abdominal wall, "through and through" the gastric antrum, to enter the stomach wall again high on the lesser curvature of the stomach ([Fig. 1], [Fig. 2] , [Fig. 3]). This transfixed the distal stomach, causing obstruction of the gastric outlet. Attempts to further assess the gastrostomy tube position by esophagogastroscopy failed. The patient's hemoglobin dropped to 5 g/dL, presumably due to the large volume of blood-stained fluid found in the stomach.
Fatal retroperitoneal gas gangrene complicating colonoscopic polypectomy without bowel perforation in a healthy adult
Authors: Evelyn Shaw, Raquel Reyes, Antonia Bonet, Lucia Garcia-Huete, Alberto Pasqualetto, Fe Tubau, Jordi Carratalà
Journal: Endoscopy (2014)

Colonoscopy is a commonly performed procedure that is rarely associated with severe complications, especially not life-threatening infections [1] [2] [3]. We report a fatal outcome caused by Clostridium perfringens after colonoscopic polypectomy in a 58-year-old healthy adult. The colonoscopy was performed as part of a public health screening program for colorectal cancer studying fecal occult blood, and during the procedure four polyps were removed.
Covered self-expandable metal stents (sems) as a new treatment option for perforated duodenal ulcer
Authors: JA Arroyo-Vazquez, PO Park, M Bergström
Journal: Endoscopy (2012)

Introduction: Surgical closure is the gold standard for treating perforated duodenal ulcers. Covered self-expandable metal stents are currently used for treating anastomotic leakages. In analogy with this treatment we started to use covered SEMS to treat perforated duodenal ulcers.
Parathyroid Hormone Hyporesponsiveness in Patients with Basal-Cell Nevi and Bone Defects
Authors: Jerome B. Block, William E. Clendenning
Journal: New England Journal of Medicine (1963)

A RARE syndrome consisting of basal-cell nevi§ and bone defects — namely, mandibular cysts and rib abnormalities1 2 3 4 — has been described. Hypertelorism, mental changes, agenesis of the corpus callosum, scoliosis, gonadal dysplasia, epithelial cysts, milia and dyskeratoses of the palms and soles have been reported as associated findings in one or more cases.No studies of calcium and phosphorus metabolism have been made in these patients. Such studies seemed in order when 1 such patient exhibited certain clinical similarities to patients with pseudohypoparathyroidism. This report concerns our findings in 2 of these patients.Case ReportCase 1. A 49-year-old woman had . . .
Abstract 4780: c-FLIP knockdown increases apoptosis in cervical cancer cell lines
Authors: Carmen Ili, Priscilla Brebi, Patricia Garcia, Cynthia LeBron, Pamela Leal, Sonia Montenegro, Alejandro Corvalan, Rafael Guerrero-Preston, Juan Carlos Roa
Journal: Cancer Research (2011)

Abstract Cervical Uterine cancer is a leading cause of cancer deaths in women worldwide. Its natural history begins gradually from low-grade and high-grades squamous intraepithelial lesions to an invasive disease. Decades of studies have confirmed a directly association between persistent high-risk Human Papillomavirus (HPV) infections and cervical cancer. However, high-risk HPV infections are not sufficient to induce cellular transformation and tumor occurrence. The cellular FLICE-like inhibitory protein (c-FLIP) has been founded overexpressed in several cancers and could be associated with cervical carcinogenesis. c-FLIP is a catalytically inactive caspase-8/-10 homologue, and when is overexpressed has the ability to inhibit the extrinsic pathway of apoptosis. Aim: To characterize c-FLIP participation in cervical carcinogenesis.Materials and Methods: Four cell lines were used in this study: ECT1 E6/E7 (squamous normal cervical epithelial), SiHa (cervical carcinoma containing an integrated HPV 16 genome), C-4I (cervical carcinoma containing an integrated HPV 18 genome) and C-33A (cervical carcinoma without HPV). c-FLIP expression in cell lines was determined by real time PCR and western blot. c-FLIP expression was transiently downregulated by siRNA directed against c-FLIP mRNA and the silencing effects on cell viability and apoptosis were analysed, by comparing with a control negative siRNA-transfected cells.Results: c-FLIP was found to be overexpressed in SiHa and C-4I cell lines and repressed in C-33A cell line. Only the long variant of c-FLIP was found in cervical cancer cell lines. Transient knockdown of c-FLIP resulted in significant reduction in cell viability (p&amp;lt; 0.001), compared with negative control siRNA-transfected cells. Knockdown cells lines exhibited an increased apoptotic rate in comparison with controls (p&amp;lt;0,001). Conclusions: The long variant of c-FLIP is overexpressed in cervical cancer cell lines with integrated genome of a high-risk HPV. Furthermore, the siRNA-mediated downregulation of c-FLIP expression induces apoptosis and decreases cell viability in cervical cancer cell lines. Therefore, this protein could be a potential therapeutic target in cervical cancer. 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 4780. doi:10.1158/1538-7445.AM2011-4780
Breast Cancer Events Associated with Germline Mutations of the CDH1 Gene (Hereditary Diffuse Gastric Cancer).
Authors: P. Hebbard, A. MacMillan, J. McCarthy, K. Laing, N. Wadden, J. Green, B. Fernandez, A. Kwan, D. Wirtzfeld
Journal: Cancer Research (2009)

Abstract Breast cancer events associated with germline mutations of the CDH1 gene (Hereditary Diffuse Gastric Cancer).Background: Mutations of the CDH1 (e-cadherin) gene are known to cause an autosomal dominant familial cancer syndrome, commonly referred to as hereditary diffuse gastric cancer. The lifetime risk of gastric cancer may be up to 80 percent. An associated risk of lobular breast cancer has been identified, but less well studied. Lifetime risk of breast cancer in affected women may be up to 50 percent.Method: We identified 17 women in our centre with known CDH1 mutations that have been offered genetic counseling for breast cancer risk. Counseling included discussion of prophylactic surgery, and breast screening via MRI/mammogram. We performed a chart review to identify breast cancer screening, prophylaxis, and treatment events in these patients.Results: 16 patients had adequate chart data to study. Of these, one patient had a breast cancer (T3N0M0) prior to mutation identification. 13 of 15 remaining patients entered into a high-risk breast-screening program with annual MRI and mammogram. Two breast cancers were identified in the first two years of patient screening; both were T1N0M0. Both women opted for bilateral mastectomy. No patient opted for prophylactic breast surgery prior to cancer detection, although several were in the process of prophylactic gastrectomy.Conclusion: To our knowledge, this is the first in-depth description of breast cancer events in patients with inherited CDH1 mutations. A majority of patients have opted for a breast-screening program, with successful early detection in two patients. Patients to date have not chosen primary prophylactic breast surgery, but two have chosen bilateral mastectomy upon detection of a malignancy. Further epidemiological studies are required to fully understand the breast cancer pattern and natural history that occurs in this genetic syndrome. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 904.
Abstract 1617: Potential therapeutic effect of glycogen synthase kinase 3β inhibition against human glioblastoma
Authors: Katsuyoshi Miyashita, Kazuyki Kawakami, Mitsutoshi Nakada, Abbas Shakoori, Hironori Fujisawa, Yutaka Hayashi, Jun-ichiro Hamada, Toshinari Minamoto
Journal: Cancer Research (2010)

Abstract Purpose: Glioblastoma represents the malignant brain tumor that is most refractory to treatment and in which the identification of molecular target(s) is urgently required. We investigated the expression, activity, and putative pathologic role of glycogen synthase kinase 3β (GSK3β), an emerging therapeutic target for neurodegenerative diseases, in human glioblastoma. Experimental Design: The active fractionof GSK3β that is phosphorylated at the tyrosine 216 residue (pGSK3βY216) was identified in glioblastoma cell lines. GSK3β activity for phosphorylating its substrate was detected in these cells by nonradioisotopic in vitro kinase assay. Results: Higher expression levels of GSK3β and pGSK3βY216 were frequently detected in glioblastomas compared with nonneoplastic brain tissues. Inhibition of GSK3β activity by escalating doses of a small-molecule inhibitor (AR-A014418) or inhibition of its expression by RNA interference induced the apoptosis and attenuated the survival and proliferation of glioblastoma cells in vitro. Inhibition of GSK3β was associated with increased expression of p53 and p21 in glioblastoma cells with wild-type p53 and with decreased Rb phosphorylation and expression of cyclin-dependent kinase 6 in all glioblastoma cell lines. Administration of AR-A014418 at a low dose significantly sensitized glioblastoma cells to temozolomide and 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea, chemotherapeutic agents used in the clinical setting, as well as to ionizing radiation. Conclusion: These results indicate thatGSK3β exerts a pathologic role by promoting the survival and proliferation of glioblastoma cells and by protecting them from apoptosis via the inactivation of p53- and/or Rb-mediated pathways (Clin Cancer Res 2009;15:887-97). Consequently, we propose that GSK3β provides a potential therapeutic target in glioblastoma (Minamoto T, inventor; National University Corporation Kanazawa University; assignee. Suppression of cancer and method for evaluating anticancer agent based on the effect of inhibiting GSK3β. International patent WO2006/073202. 2006 Jul 13. United States patent US 11/794,716. 2006 Jan 4. European patent EP1845094 2007 Oct 17. Japan patent 2006-550915 2007 Jun 21). 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 1617.
Bleeding Gastrointestinal Stromal Tumor of the Jejunum Detected by a Tc-99m Red Blood Cell Gastrointestinal Bleeding Scan
Authors: SHUNG-SHUNG SUN, SHIH-CHUAN TSAI, HSUAN-HUA HUANG, CHIA-HUNG KAO
Journal: Clinical Nuclear Medicine (2001)

SUN, SHUNG-SHUNG M.D.; TSAI, SHIH-CHUAN M.D.; HUANG, HSUAN-HUA M.D.; KAO, CHIA-HUNG M.D. Author Information
Baby Steps on the Road to HIV Eradication
Authors: Scott M. Hammer
Journal: New England Journal of Medicine (2013)

The durable suppression of plasma human immunodeficiency virus type 1 (HIV-1) RNA that is conferred by potent antiretroviral therapy (ART) has been associated with dramatic improvements in immunologic and clinical well-being and reductions in morbidity and mortality from opportunistic complications. It has also brought the restoration of normal life expectancies within our grasp, has effectively eliminated the vertical transmission of HIV in resource-unconstrained settings in women who receive antenatal care, and can substantially reduce horizontal transmission.1 Concomitantly, the ability to drive plasma HIV-1 RNA to levels below the limits of quantification of sensitive clinical assays has unveiled the limitations of . . .
P461New targets of therapy at rheumatoid vasculitis: focus on microcirculation
Authors: D Bublikov, A Andrienko
Journal: Cardiovascular Research (2014)

The rheumatoid vaskulitis (RV) strikes about a quarter of patients with rheumatoid arthritis, causing defeat of visceral bodies and systems, a cachexy and progressing of articulate destruction. Therefore RV treatment - an actual problem of modern rheumatology. Aim: To study microcirculation at sick RV and possibility of its improvement the pentoxifyllini. Materials and methods: Research included women, patients rheumatoid artritis (n=69). Middle age - 55,54±3,22 years. Having positive antibodies to cyclic citrullined peptide (ACCP) and a positive rheumatoid factor in blood. All patients received DMARD-therapy. Microcirculation was investigated by a method of a laser Doppler flowmetri on forearm skin. Two groups of patients - intact (n=39), not receiving a preparation and research (n=30), receiving a preparation are allocated. Pentoxifyllin was entered in an average dose of 800 milligrams per day.Research was conducted within two weeks. Statistical processing carried out by means of Mann-Whitney methods. Results: Microcirculation in the first group made 14,28±5,21 perfusion units. In the second group - 19,24±2,65 perfusion units that made statistically significant difference (p=0,00032). Clinically patients of intact group had no dynamics. The patients receiving in addition to DMARD therapy pentoxifyllin (the second group) had positive clinical dynamics of articulate and visceral syndromes. Moreover, statistically significantly lower CRP levels (p=0,0043). Conclusion: Pentoxifyllin inclusion in a dose of 800 mg per day leads to positive clinical and laboratory dynamics at patients rheumatoid vaskulitis and can be a new target for therapy.
False-Positive Antimyosin Imaging Caused by Cardioversion-induced Skeletal Muscle Uptake
Authors: J L Alberini, D Pavin, J C Daubert, P Bourguet
Journal: Clinical Nuclear Medicine (1999)

In-111 antimyosin imaging was performed to identify a recent myocardial infarction in a 46-year-old man who was resuscitated after cardiac massage and cardioversion. Six days after admission, planar anterior and left anterior oblique views (at 45- and 70-degree angles) and SPECT were performed 48 hours after injection of In-111 antimyosin. Uptake was observed in the anterior thoracic wall and the left flank. This uptake could be explained by muscle necrosis induced by the electroshock. Similar cases have been reported with Tc-99m pyrophosphate.