tbuckley/cabot-search huggingface dataset:
Abstract 2589: Robust in vitro anti-tumor activity of Trastuzamab antibody drug conjugates in HER2 amplified cell lines
Authors: Sankar Mohan, Carol O'Brien, Heidi Savage, Gail Phillips, Mark Lackner, Ajay Pandita
Journal: Cancer Research (2010)

Abstract Breast cancer is a heterogeneous disease with molecular subtypes characterized by distinct gene expression signatures and histopathology. The defining characteristic of the HER2-amplified subtype is high-level amplification of the HER2 oncogene and overexpression of HER2 protein. Assays for protein overexpression and chromosomal amplification are currently used as diagnostic markers to select patients for HER2-targeting therapies. In the current study, we compared the sensitivity of several HER2-targeting therapies across a panel of 31 breast cancer cell lines and correlated the sensitivity of the cell lines with HER2 positivity detected by IHC, qPCR and FISH. The agents used in screening were trastuzamab, two antibody-drug conjugates (ADCs) consisting of trastuzamab conjugated to an anti-mitotic agent, and a small molecule inhibitor of HER2 kinase activity. HER2 testing revealed 32% of the cell lines to be positive for HER2 by qPCR and FISH, and 90% of these demonstrated a high-level amplification as demonstrated by HER2 amplifications in the form of clusters by FISH and more than 10 copies by qPCR. Several of the cell lines showed polysomy for chromosome 17 and extra copies of HER2 by FISH assay but did not meet the criteria for HER2 amplification. The HER2 IHC assay showed 10 cell lines to be positive (2+, 3+) by IHC, with 8 illustrating high-level expression (3+). The agents tested were more efficacious in the HER2-amplified cell lines, with the broadest activity observed in response to the ADCs. Cell lines exhibiting polysomy for HER2 and 1+ expression by IHC were less responsive to any of the agents tested. Consistent with previous reports, many of the cell lines resistant to trastuzamab or the small molecule HER2 inhibitor demonstrated deregulation of the PI3K pathway illustrated by mutations in the PIK3CA gene or loss of PTEN protein expression. Interestingly, the majority of these resistant cell lines were sensitive to ADCs. In summary, our study illustrates a high sensitivity of ADCs in breast cancer cell lines harboring a high-level amplification of the HER2 gene and suggests these agents may overcome in vitro resistance provided by activation of the PI3K pathway. 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 2589.
Intensive conventional-dose chemotherapy for stage IV low-grade lymphoma: High remission rates and reversion to negative of peripheral blood bcl-2 rearrangement
Authors: P. McLaughlin, F.B. Hagmeister, F. Swan, F. Cabanillas, J. Romaguera, M.A. Rodriguez, M.S. Lee, O. Pate, A. Sarris, A. Younes
Journal: Annals of Oncology (1994)
Tc99m-Sestamibi Thigh SPECT/CT Images for Noninvasive Assessment of Skeletal Muscle Injury in Carbon Monoxide Intoxication With Clinical and Pathological Correlation
Authors: Shu-Hua Huang, Wen-Neng Chang, Shu-Fang Chen, Pei-Wen Wang, Chun-Chung Lui, Min-Chien Tu, Chen-Chang Lee, Yung-Cheng Huang, Bor-Tau Hung, Ssu-Wei Chen, Chiung-Chih Chang
Journal: Clinical Nuclear Medicine (2011)

Muscle weakness has been repeatedly reported in patients with carbon monoxide (CO) intoxication. In animal models, CO intoxication has been linked with mitochondrial electron transport dysfunction. The objectives of the present study were to use Tc-99m sestamibi thigh single-photon emission computed tomography/computed tomography (SPECT/CT) to evaluate the mitochondrial status in patients with CO intoxication, correlate this with clinical parameters, and compare with age-matched controls.A total of 25 patients with delayed sequelae after CO intoxication (range: 1-60 months) and 17 sex- and age-matched healthy volunteers underwent Tc-99m sestamibi thigh SPECT/CT. Cognitive evaluation and muscle power according to medical research council (MRC) grading were collected. Both visual scoring from planar images and automatic volumetric analysis were used to rate the Tc-99m sestamibi uptake level.The visual scores showed that 14 patients (56.0%) were scored as moderate-to-severe decrement. Volumetric analysis showed that a significant Tc99m-sestamibi uptake decrement was found in the CO intoxication group as compared with the controls, and 16 patients (64.0%) had uptakes below 1 standard deviation of the control group. In the CO group, the muscle power but not the cognitive evaluation correlated with Tc-99m sestamibi uptake in muscles. The decrement of muscle Tc99m-sestamibi uptake was related to mitochondria swelling, increased mitochondrial numbers, and type II muscle atrophy in 1 patient.In this study, we demonstrated that patients with CO intoxication sustained defective mitochondrial metabolism in skeletal muscles as revealed by a decrement in Tc-99m sestamibi uptake either by visual or semiquantification of thigh SPECT/CT. Tc-99m sestamibi scanning provided noninvasive measurement of mitochondrial injury in muscles after CO intoxication and the correlation with clinical parameters was good.
Treatment of Severe Malaria in the United States with a Continuous Infusion of Quinidine Gluconate and Exchange Transfusion
Authors: K D Miller, A E Greenberg, C C Campbell
Journal: New England Journal of Medicine (1989)

During the past decade the incidence of Plasmodium falciparum malaria in the United States has increased 10-fold. Treatment may be delayed because the therapy recommended for severe or complicated disease, intravenous quinine dihydrochloride, is available only from the Centers for Disease Control. We studied 17 patients who were treated for severe or complicated P. falciparum malaria in the United States between 1985 and 1987. Five patients were treated with a continuous infusion of quinidine gluconate, 10 with an exchange transfusion in addition to the continuous infusion of quinidine gluconate, and 2 with intermittently administered intravenous quinine dihydrochloride and an exchange transfusion. All 16 patients with P. falciparum malaria (1 patient had P. vivax malaria) had hyperparasitemia at the time of diagnosis (6 to 54 percent of the erythrocytes infected; median, 13 percent). Three patients with marked hyperparasitemia (54, 38, and 30 percent) and multiple other indicators of a poor prognosis, including advanced age, died. The 13 patients who completed their courses of quinidine with or without exchange transfusion had a parasitemia level of 1.1 percent or less 28 to 72 hours (mean, 44.4 hours) after the start of therapy. Side effects of quinidine treatment were observed in only two patients, one of whom had a serum quinidine concentration above the toxic level. We conclude that the continuous infusion of quinidine gluconate is well tolerated alone and with exchange transfusion and is effective in the treatment of severe and complicated malaria.
Abstract 642: Body fat distribution and prostate cancer risk: A UK case-control study
Authors: Fredie Robinson, Artitaya Lophatananon, Aneela A. Rahman, Sarah S. Brown, Terence L. Parker, Douglas Easton, Zsofia K. Jarai, Richard Pocock, David Dearnaley, Michelle Guy, Rosemary A. Wilkinson, Emma S awyer, Elizabeth Page, Jo-Fen Liu, Anna Grabowska, David Walker, Amanda L. Hall, Rosalind A. Eeles, Kenneth R. Muir
Journal: Cancer Research (2012)

Abstract Background: Prostate cancer is the most common cancer among males in the UK and in 2007 accounted for almost a quarter of all male cancers diagnosed. Previous studies have shown some associations between body size/obesity and prostate cancer risk. However body fat distribution in terms of perceived “body shape” and its association with prostate cancer risk has never been described. Methods: In the UK data from 1343 cases and 817 controls with age ranged between 38 and 85, with mean age 62.4 (SD 6.2) were collected between 2007 -2009 as part of the UKGPCS Prostate Cancer Study. The data on subjects’ body fat distribution type including “apple” (body fat mostly around the waist and upper trunk), “pear” (body fat around hips), “oval” (body fat generalised on whole body) and “symmetrical” were obtained through self report diagrams in questionnaires after consent from the subjects. Unconditional logistic regression analysis, with adjustment for age, education, ethnic, family history and lifetime body shape size as potential confounders, were carried out to obtain odds ratios and confidence intervals for different types of body fat distribution to assess their possible association with risk of prostate cancer. Results: A “symmetrical” body shape was used as the reference category. Subjects with an “apple” shape were at a significantly 30% reduced risk (adjusted OR 0.70 with 95% CI: 0.55-0.89). Subjects with an “oval” or “pear” shapes did not show any statistically significant association. Conclusion: An “apple” body fat distribution was associated with reduced prostate cancer risk when compared to symmetrical shape. 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 642. doi:1538-7445.AM2012-642
Tc-99m MIBI Parathyroid Scintigraphy and Intact Parathyroid Hormone Levels in Hyperparathyroidism
Authors: GUANG-UEI HUNG, SHYH-JEN WANG, WAN-YU LIN
Journal: Clinical Nuclear Medicine (2003)

Tc-99m MIBI has been widely used to evaluate hyperparathyroidism based on increased tracer uptake in hyperfunctioning parathyroid tissue. The functional status measurement of parathyroid glands with intact parathyroid hormone (iPTH) levels is also one of the most important diagnostic studies in this disorder. The aim of the current study was to assess the relation between MIBI imaging and iPTH levels. The authors retrospectively reviewed the records of patients with hyperparathyroidism who were referred to their department for Tc-99m MIBI scintigraphy. Sixty-five patients (24 primary and 41 secondary hyperparathyroidism) were included. The iPTH levels ranged from 66.06 to 2,836 pg/ml (normal, 10 to 55 pg/ml). Forty-two patients were MIBI positive and 23 were negative. The iPTH level in the MIBI-positive group was significantly greater than in the negative group in the primary (548 ± 478 versus 124 ± 45;P = 0.002), secondary (1,155 ± 692 versus 501 ± 352;P < 0.001), and overall (909 ± 678 versus 386 ± 341;P < 0.001) groups. For the primary hyperparathyroidism group, 17 of the 24 patients were MIBI positive (71%). When iPTH levels exceeded 200 pg/ml (100%), the diagnostic sensitivity reached 100%. For the secondary hyperparathyroidism group, 25 of 41 patients (61%) were MIBI positive; 24 of 38 patients (63%) had an iPTH level greater than 200 pg/ml, 21 of 27 patients (78%) had an iPTH level greater than 500 pg/ml, and 11 of 12 patients (92%) had an iPTH value greater than 1,000 pg/ml. Tc-99m MIBI parathyroid scintigraphy showed a good correlation with iPTH level for both primary and secondary hyperparathyroidism. Visualization of hyperfunctioning parathyroid glands on Tc-99m MIBI parathyroid scintigraphy was more likely with a higher serum iPTH level in a dose-dependent manner.
Psychoanalysis of Heart Attack
Authors: Frank J. Ayd
Journal: JAMA (1968)

For many years, Dr. Daniel Schneider, a psychoanalyst of the freudian school, has been studying patients with various heart conditions, including coronary artery disease. He also has striven to keep abreast of research developments with respect to the mind-heart and heart-mind relationships. As a result he has evolved new theories about the manner in which a part of the mind functions as a monitor of the heart. These are set forth in this book, which is intended for the professional and lay reader. To understand and fully appreciate Dr. Schneider's concepts, this book must be studied carefully. The basic premises are complex, but because of redundancy, of a wordiness that results in obscurity, and of the need for the reader to be acquainted with at least elemental psychoanalytic terminology and concepts, this is a book which the average reader—professional or lay —will not find easy to peruse and digest. This
Treatment of Acute Leukemia in Adults with Massive Doses of Prednisone and Prednisolone
Authors: Norma B. Granville, Fernando Rubio, Asuman Unugur, Edward Schulman, William Dameshek
Journal: New England Journal of Medicine (1958)

THE treatment of acute leukemia of adults has been attended with considerable disappointment. The folic acid antagonists, although occasionally productive of well defined remissions, ordinarily have no value. 6-mercaptopurine gives somewhat more frequent remissions, and with less toxicity than aminopterin, but a remission rate of 10 to 15 per cent in our hands is not particularly encouraging. Relatively small doses of the adrenocortical steroids have been useful in producing minor remissions with marked symptomatic improvement, as well as in controlling fever, hemorrhage, malaise and bone pain. However, because of the marked sodium-retaining property of the first products produced, the use . . .
Case 34-2003
Authors: Daniel C. Chung, Mari Mino, Kristen M. Shannon
Journal: New England Journal of Medicine (2003)

Presentation of CaseA 45-year-old woman came to the outpatient clinic for counseling because of concern about a family history of colonic polyps and cancer.The patient felt well and had had no abdominal pain, change in bowel habits, rectal bleeding, or weight loss. She had had no operations and took no medications. A colonoscopic examination had been performed for screening purposes four years earlier, and no polyps had been identified. She did not smoke and rarely consumed alcohol.The patient's mother was 80 years old and had been given a diagnosis of colon cancer at 75 years of age. . . .
Abstract P2-04-07: Modeling orthotopic and metastatic progression of mammary tumors to evaluate the efficacy of TGF-β inhibitors in a pre-clinical setting
Authors: T Biswas, J Yang, L Zhao, L Sun
Journal: Cancer Research (2012)

Abstract Preclinical models are elemental in understanding drug efficacy and safety in vivo. Many existing models of breast cancer metastasis use immune compromised animals and do not effectively characterize the differential stages of metastasis. Transforming growth factor-β (TGF-β) has been shown to be a major contributor in epithelial-mesenchymal transition and enhances various steps during metastasis. The aim of this study is to develop mouse models of tumor metastasis using murine mammary cells in a syngeneic background. This will help illustrate the effect of TGF-β inhibitors on metastasis in an immune competent environment, and also allow determining the optimal time of drug administration. We demonstrate that TGF-β signaling has differential effects on a pair of murine mammary cell lines derived from PyMT tumors in C57Bl/6 mice. These cell lines represent luminal (Py 230) and basal (Py 8119) epithelial cell populations in the tumor. In vitro characterization revealed differences in viability, motility, and transcriptional and translational activation of Smad. Py 230 (clonal luminal) cells are growth inhibited and exhibit epithelial-mesenchymal transition on treatment with TGF-β, whereas Py 8119 (basal cells) are non-responsive to both effects. Furthermore, intra cardiac injections were performed using luciferase-GFP labeled PyMT cells in syngeneic background and animals were treated with either placebo or TβRI-KI (kinase inhibitor for TGF-β receptor I). Results from Py 8119 cell injections showed that TβRI-KI treatment enhanced bone and brain metastases. Further results will shed light on the effect of TβRI-KI during specific stages of metastasis progression. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-04-07.
Abstract P2-05-08: Determination of HER2 amplification by dual-color in situ hybridization before and after neoadjuvant chemotherapy
Authors: N Niikura, N Kumaki, T Iwamoto, B Tsuda, T Okamura, S Yuki, Y Suzuki, Y Tokuda
Journal: Cancer Research (2012)

Abstract Background: HER2-targeted therapies such as trastuzumab neoadjuvant chemotherapy for patients with HER2-positive breast cancer can increase pathological complete response (pCR) better than non-HER2-targeted therapies. Previous studies have suggested that trastuzumab may convert HER2-positive (HER+) primary breast tumors to HER2 negative (HER−) after neoadjuvant chemotherapy. We compared the HER2 status in breast cancer patients before and after neoadjuvant treatment by using dual-color in situ hybridization (DISH). Methods: We retrospectively identified 46 patients from the Breast Cancer database at Tokai University Hospital, in whom HER2-positive primary breast cancer was diagnosed between 2000 and 2010, and who were treated with neoadjuvant chemotherapy or endocrine therapy with or without trastuzumab. Surgical specimens from patients achieving less than pCR were assessed to determine if there was enough residual tissue to evaluate the post-treatment HER2 status by DISH. HER2 status was defined as positive if DISH demonstrated a gene copy ratio of HER2:CEP17 &amp;gt;2.0. Paraffin tissue sections (4-μm thick) were mounted on glass slides (New Sliane III, Catalog No. 5126–25; MUTO PURE CHEMICALS, CO. LTD., Tokyo, Japan) and stained using the newly developed, fully automated HER2 Dual ISH assay on a BenchMark® XT slide stainer according to the recommended procedure (Ventana Medical Systems Inc., Tucson, AZ). Thereafter, the stained slides were rinsed with tap water containing neutral detergent and then rinsed again with distilled water. The slides were dried at room temperature for at least 60 min and cover-slipped with cover grass for SGC (MUTO PURE CHEMICALS). HER2 Dual ISH and H&amp;E images were obtained using an Olympus BX51 microscope. Results: A pCR was achieved in 9 of the 46 patients (19.6%). Specimens from core needle biopsy were not sufficient to assess the pretreatment HER2 status in 3 patients. In 9 patients, the post-treatment HER2 status could not be assessed because residual tumors were DCIS only in 4 patients and there were less than 20 invasive cells in 5 patients. Residual tumor was sufficient to assess the post-treatment HER2 status in 25 patients. In pretreatment specimens, of the 25 patients identified as HER2 + by immunohistochemical analysis, 3 patients were identified as HER2− by DISH. No post-treatment specimens were found to be HER2− by DISH among the tumors identified as HER2+ by DISH at pretreatment. Among the 3 pretreatment tumors identified as HER2− by DISH, 1 tumor was found to be HER2+ by DISH at post-treatment, and 2 showed a stable HER2 status. Conclusion: DISH revealed a stable HER2 status in pretreatment breast tumors and in residual tumors. However, we found a discrepancy in the HER2 status between the immunohistochemical analysis and DISH. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-05-08.
Reduction to Normal of Plasma Glucose in Juvenile Diabetes by Subcutaneous Administration of Insulin with a Portable Infusion Pump
Authors: William V. Tamborlane, Robert S. Sherwin, Myron Genel, Philip Felig
Journal: New England Journal of Medicine (1979)

To improve plasma glucose control, we administered insulin via the subcutaneous route in seven ambulatory patients with juvenile diabetes (12 to 17 years of age), using a portable infusion pump at a basal rate with pulse-dose increments before meals. After two to four days, the mean plasma glucose (±1 S.E.) of 94±5 mg per deciliter was markedly lower than when insulin was given by conventional methods in the patients' usual dose (243±28, P<0.01) or in a total dose equivalent to that administered with the pump (150±15, P<0.01). Maximal fluctuations in plasma glucose were also 50 to 150 mg per deciliter below those observed with conventional treatment (P<0.001). Glycosuria was eliminated in six of seven patients during pump treatment. None of the subjects had hypoglycemia. These results demonstrate that plasma glucose can be lowered to normal in ambulatory patients with brittle juvenile diabetes using a portable, subcutaneous insulin infusion system for two to four days. The feasibility and value of the long-term application of this technic need exploration. (N Engl J Med 300:573–578, 1979)
Abstract 2362: Antimetastatic potential of the antiprogestin mifepristone in cancer cells
Authors: BreeAnn N. Brandhagen, Chelsea R. Tieszen, Carlos M. Telleria, Alicia A. Goyeneche
Journal: Cancer Research (2011)

Abstract For most cancers, it is metastasis and burden of the secondary tumors that account for nearly 90% of cancer-related mortality. The process of metastatic dissemination of tumor cells is extremely complex. Among the critical parameters involved in metastatic spread are cellular detachment from the initial tumor, migration, invasion and adhesion to secondary sites, all processes associated with changes in cell morphology caused by cytoskeletal rearrangements. Our laboratory previously demonstrated that the synthetic antiprogestin mifepristone (MF) inhibits the growth of cancer cells of reproductive and non-reproductive origin. We also observed that in response to MF, the cells displayed drastic changes in morphology. Due the impact of cell structure on the metastatic process, this study questioned whether MF has anti-metastatic potential deregulating key processes required for metastatic dissemination. Cancer cell lines of the ovary (SK-OV-3), breast (MDA-MB-231), prostate (LNCaP), and brain (U87MG) were chosen from a panel of cell lines in which we previously observed cytostatic activity of MF associated with changes in cellular morphology. Cell cultures were exposed to vehicle or MF for 72 h at which point we examined the morphology of the cells, the distribution of cytoskeletal proteins actin and tubulin, the adhesion capacity to components of the extracellular matrix, and the cell migratory and invasive properties. MF induced distinct morphology changes after 48 h exposure, independent of the density of the cell culture population. Interestingly, MF induced similar morphology changes in all cell lines, which included shrinkage of the cell body, long, thin cellular extensions, and a loss of cell-to-cell connections. Morphology changes were associated with rearrangement of actin and tubulin filaments. Upon removal of MF, cell morphology and proliferation returned to that of untreated cultures in all cell lines expect for LNCaP. For all cell lines, MF caused accelerated trypsin-induced detachment and decrease in cell adhesion to various extracellular matrix substrates suggesting that MF may impair re-adhesion of cells en route to colonize a secondary location. Moreover, MF significantly inhibited the ability of cells to migrate in wound healing and Boyden chamber assays, as well as their capacity to invade through extracellular matrix-coated polycarbonate membranes. Overall this study suggests that antiprogestin MF could be of potential therapeutic use, not only as a cytostatic agent impairing tumor growth, but also to halt metastatic spread of tumor cells. (Supported by NCI grants K22CA121991 and K22CA121991S1). 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 2362. doi:10.1158/1538-7445.AM2011-2362