tbuckley/cabot-search huggingface dataset:
The influence of bisphosphonates on bone turnover markers in patients (pts) with breast cancer (BC)
Authors: A. Keller, K. Heim, G. Welzel, P. Findeisen, M. Neumaier, F. Wenz
Journal: Journal of Clinical Oncology (2009)

1058 Background: The relevance of the bone metabolism for the prognosis of BC pts is becoming widely accepted. Bisphosphonates are increasingly used in BC pts as prophylactic (antitumor benefits) or as therapeutic agents for the prevention of skeletal related events (SREs). The bone resorption marker peptide-bound collagen type I cross-links C-telopeptides (ICTP) and the bone formation marker N-terminal propeptide of type I collagen (PINP) may become important tools to monitor the bone metabolism and may be influenced by co-medication. Methods: ICTP and PINP were measured in serum samples (n = 252) under standardized conditions. We included BC pts without (n=118, 58±11 yrs) and with bone metastases (BM, n=23, 64 + 12 yrs). For comparison 111 prostate cancer (PC) pts without (n = 84, 70 ± 6 yrs) and with BM (n = 27, 67 ± 10 yrs) were investigated. Results: The median ICTP (5.41 vs 4.34 ug/l, p = 0.04 [Mann-Whitney test]) and PINP (44.9 vs 36.3 ug/l, p = 0.08) values were higher in BC pts with BM as compared to no BM. The presence of BM (&lt; 3 vs 1–3 mets) increased ICTP and PINP values further, whereas bisphosphonates lead to a significant reduction in PINP to normal values in these pts (58.3 vs 32.8 ug/l, p = 0.01). Tamoxifen increased ICTP (4.85 ± 1.8 ug/l) and decreased PINP (36.7 ± 14.3 ug/l), whereas aromatase inhibitors (AIs) increased ICTP (4.93 ± 1.7 ug/l) and PINP (49.4 ± 24.7 ug/l). The same effects were seen in PC pts with and without BM, LHRH had a similar effect like AIs, whereas the impact of antiandrogens was like tamoxifen. Age and gender had no significant influence on ICTP or PINP in BC and PC pts. Conclusions: Markers of bone metabolism may be useful for the diagnosis and follow-up of pts with BC and PC with and without BM. Bone metastases and aromatase inhibitors increased serum ICTP and PINP, whereas bisphosphonates induced a significant decrease in serum PINP. [Table: see text]
Isolated Left Hepatic Lobe Cholestasis Demonstrated on Cholescintigraphy
Authors: A Bhatnagar, R Chand, P Mishra, M K Chopra, K Sawroop
Journal: Clinical Nuclear Medicine (2000)

Cholescintigraphy was performed on a man of normal physique with a history of recurrent fever and moderately increased serum enzyme levels after biliary surgery. It revealed cholestasis in the entire left lobe of the liver that persisted 24 hours after injection, along with a small subhepatic biliary leak. The study was repeated 1 year later, when the patient had remained asymptomatic with normal results of biochemical tests for more than 6 months. Although the biliary leak had disappeared, nearly total left lobar cholestasis was again apparent for 24 hours. Ultrasound, computed tomography, and magnetic resonance imaging revealed no parenchymal abnormality, suggesting the absence of inflammatory liver disease. A developmental vascular anomaly allowing more of the tracer to flow to the left lobe or an anomaly of the intrahepatic biliary system limited to the left liver lobe are possible causes of these findings.
Disappointing Results With Tc-99m Tetrofosmin for Detecting Medullary Thyroid Carcinoma Metastases Comparison With Tc-99m VDMSA and Tl-201
Authors: IŜIK ADALET, PELIN DEMIRKALE, SEHER ÜNAL, HARIKA OŮZ, FARUK ALAGÖL, SEMA CANTEZ
Journal: Clinical Nuclear Medicine (1999)

Purpose: This prospective study assessed the detectability of metastatic lesions by Tc-99m tetrofosmin in medullary thyroid carcinoma and to compare the results with Tc-99m penta dimercapto succinic acid (VDMSA) and Tl-201. Methods: A prospective study was performed on 24 patients (10 men, 14 women; ages 23 to 76 years) with medullary thyroid carcinoma after total thyroidectomy. Five cases were sporadic and 19 were familial. After the injection of 740 MBq (20 mCi) tetrofosmin, 740 MBq (20 mCi) VDMSA and 74 MBq (20 mCi) Tl-201, whole-body scans and 5-minute static images of the head, neck, chest, abdomen and pelvis were obtained. All scintigraphic studies were compared with calcitonin levels, radiologic findings, histopathologic results, and clinical follow-up. Results: Thirty-four metastatic sites were detected in 12 patients on the basis clinical, radiologic, and histopathologic findings. Patients were divided into three groups according to the calcitonin levels and scintigraphic findings. Group 1 consisted of patients with elevated calcitonin levels and positive scintigraphic findings. Among 34 metastatic sites, 30 could be detected with VDMSA. Only 21 and 20 metastatic sites could be visualized with Tl-201 and tetrofosmin, respectively. All 30 lesions showed intense VDMSA uptake but only faint or no uptake with Tl-201 and tetrofosmin. Patients in group 2 were accepted to have micrometastases. In this group, calcitonin was minimally elevated, and the results of all three scintigraphs were negative. Group 3 included patients with true-negative results. All patients had normal calcitonin levels and negative results of scintigraphic studies. Conclusions: Tetrofosmin has no role in the detection of medullary thyroid carcinoma metastases. These results show that VDMSA is clearly superior to Tl-201 and tetrofosmin in the follow-up of patients with medullary thyroid carcinoma.
OP0117 Cyclophosphamide Pulse Therapy Leads to T Regulatory Cells Alterations in Active Systemic Lupus Erythematosus
Authors: K. Tselios, A. Sarantopoulos, I. Gkougkourelas, A. Papagianni, P. Boura
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Cyclophosphamide has been proved to be efficacious in remission induction in lupus nephritis (LN) and neuropsychiatric systemic lupus erythematosus (NPSLE), probably by a non-specific ablation of reactive lymphocytes. However, little is known in regard to its effect on T regulatory cells (Tregs). <h3>Objectives</h3> <b>Objective</b> of this study was to investigate the influence of cyclophosphamide pulse therapy on the CD4+CD25<sup>high</sup>FOXP3+ Tregs in patients with active LN and NPSLE. <h3>Methods</h3> Ten Caucasian lupus patients (selected from a cohort of 200 lupus patients followed up regularly in our Unit) were included. Six patients had active LN class IV-V (mean age 33.8±8.8 years, mean disease duration 87.2±63.4 months, mean proteinuria level 2576±3985mg/24h) and 4 active NPSLE (mean age 35.5±8.8 years, mean disease duration 103.8±55.1 months; clinical manifestations: 1/4 acute confusional state, 1/4 psychosis, 2/4 refractory seizures). Cyclophosphamide was administered at monthly pulses (500mg/m<sup>2</sup>/month for six months), while doses of all other administered drugs, including steroids, remained stable or lower throughout the study. CD4+CD25<sup>high</sup>FOXP3+ Tregs were assessed by flow cytometry at baseline and before every subsequent cyclophosphamide pulse and 3-6 months after the final pulse. Disease activity was assessed by SLE Disease Activity Index (SLEDAI). <h3>Results</h3> In LN patients, Tregs were gradually increased from pulse to pulse. This increment reached statistical significance after the 4<sup>th</sup> pulse (0.54±0.20% vs. 1.27±0.32%, <i>p</i>&lt;0.001), while SLEDAI was significantly decreased (15.2±6.8 vs. 2±1.6, p&lt;0.001), along with proteinuria (2576±3985mg/24h to 234±86mg/24h, p&lt;0.001). Likewise, in NPSLE, Tregs were significantly increased after the 4th pulse (0.57±0.23% vs. 1.41±0.28%, p&lt;0.001) with a parallel SLEDAI reduction (17.8±7.7 vs. 2.1±1.6, p&lt;0.001). <h3>Conclusions</h3> Cyclophosphamide pulse therapy leads, over time, to a significant increase of the CD4+CD25<sup>high</sup>FOXP3+ Tregs in patients with active LN and NPSLE. Although this effect is probably indirect, it may partially reflect the restoration of lost tolerogenicity through the suppressive effect of cyclophosphamide on autoreactive lymphocytes. <h3>Disclosure of Interest</h3> None Declared
Abstract 2149: Cooperation of Notch and RAS/MAPK pathway leads to poor outcome in breast cancer patients
Authors: Suruchi Mittal, Rekha V. Kumar, Annapoorni Rangarajan
Journal: Cancer Research (2012)

Abstract Breast cancer is a leading cause of cancer-related deaths in women the world over, particularly in the Western population. However, emerging trends indicate an alarming rise in breast cancer incidences in other parts of the world including India. A major impediment in breast cancer treatment is occurrence of metastasis leading to poor prognosis and survival in certain patients. Therefore understanding the molecular pathways responsible for such phenomenon is critical. Recent studies have implicated aberrant Notch signaling in breast cancers. We undertook an extensive study analysing the expression of the Notch pathway members in breast biopsies of Indian origin. We observed increased expression of several Notch receptors including Notch 1, 2 3, and 4, Notch-ligands including Jagged1, Jagged2, and Delta-like 4, and downstream targets of the Notch pathway Hes1/Hes5 in breast cancer tissues compared to the normal counterpart. Additionally, we detected cleaved (active) Notch1 and Hes1/5 in early precursors of breast cancers - hyperplasia and ductal carcinoma in situ - suggesting that aberrant Notch activation may be an early event in breast cancer progression. In in vitro transformation experiments, we observed that while constitutively active Notch1 alone failed to transform HMLE immortalized breast cells, it synergized with the Ras/MAPK pathway to mediate transformation in vitro. Interestingly, compared to only cleaved Notch positive cases, those positive for both pERK1/2 and Notch showed poor survival, and majority of such cases were triple negative breast cancers. This suggests that in highly aggressive triple negative breast cancers that exhibit poor survival, the Notch and Ras/MAPK pathway cooperation might play a crucial role and thus targeting these two pathways together might offer a novel therapeutic strategy for this aggressive form of 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 2149. doi:1538-7445.AM2012-2149
Release of enzymes from adult rat heart myocytes.
Authors: M P Murphy, C Hohl, G P Brierley, R A Altschuld
Journal: Circulation Research (1982)

The release of lactic dehydrogenase, creatine phosphokinase, and aspartate aminotransferase from initially viable, metabolically competent adult rat heart myocytes has been examined. Freshly isolated cells contain levels of total lactic dehydrogenase, creatine phosphokinase, and aspartate aminotransferase, as well as lactic dehydrogenase and creatine phosphokinase isoenzyme profiles that are quite comparable to those of intact heart tissue. When the cells are lysed with digitonin, 89% of total lactic dehydrogenase, but only 58% of creatine phosphokinase and 27% of aspartate aminotransferase are released. The retention of creatine phosphokinase by the digitonin-lysed cells is accounted for by complete retention of mitochondrial creatine phosphokinase and 20% of MM-creatine phosphokinase. When intact myocytes are incubated under anoxic, substrate-deprived conditions, there is a gradual loss of the three enzymes to the suspending medium and a parallel increase in the fraction of the cells permeable to trypan blue. The fraction of freely soluble cytoplasmic enzymes lost was equivalent to the fraction of the cells permeable to the dye over a wide range of viability (17-95% viable by dye exclusion criteria), but permeable cells retained mitochondrial creatine phosphokinase and particulate aspartate aminotransferase. These results suggest that simultaneous and complete release of soluble cytoplasmic enzymes occurs as each individual cell sustains sarcolemmal damage.
International Study of Wheezing in Infants (EISL) - phase 3, São Paulo - SP, Brazil
Authors: C.S. Aranda, E.O. Dantas, J.A. Soares, L. Fonzar, A.C. Dela Bianca, G.F. Wandalsen, J. Mallol, D. Sole
Journal: Journal of Allergy and Clinical Immunology (2012)
FREQUENCY AND PREDICTORS OF WOUND FORMATION IN RUTHERFORD CATEGORY 4 PATIENTS AFTER ENDOVASCULAR THERAPY
Authors: Shirai Shigemitsu, Yoshiaki Ito, Tsuyoshi Sakai, Keisuke Hirano, Masahiro Yamawaki, Motoharu Araki, Norihiro Kobayashi, Hideyuki Takimura, Yasunari Sakamoto, Shinsuke Mori, Masakazu Tsutsumi, Takuro Takama, Hiroya Takafuji, Takashi Maruyama, Yohsuke Honda, Kenji Makino, Takahiro Tokuda
Journal: Journal of the American College of Cardiology (2016)
Prognostic Value of mib-1 in Patients with Early Invasive Breast Cancer and Its Correlation with Other Biologic Parameters in a Monoinstitutional Series.
Authors: A. Ferro, M. Barbareschi, C. Eccher, A. Caldara, M. Frisinghelli, R. Triolo, D. Aldovini, M. Pellegrini, D. Bernardi, E. Galligioni
Journal: Cancer Research (2009)

Abstract INTRODUCTION: Mib-1 is a proliferation biomarker and a prognostic factor for breast cancer as reported in several studies.PURPOSE: The aim of the present study was to examine interactions between mib-1 and other clinical-pathological markers and their impact on outcomes in early invasive breast cancer.PATIENTS AND METHODS: Mib-1 was identified by immunohistochemical staining in 2660 EIBC patients treated in our institution from 2000 to 2008. Mib-1 was dichotomized at the value of 20%. Correlation between mib-1 (&amp;gt; or ≤10620%) and age, tumour size (T), nodal status (N), ER, PR, HER-2, grading (G) was performed by χ2 test. Log-rank test and Cox regression model were performed to test mib-1 as prognostic factor for overall survival (OS) and Disease Free Survival (DFS) and evaluate its correlation with other known prognostic factors.RESULTS: Mib-1 was &amp;gt; 20% in 1276 and ≤106 20% in 1384. Mib-1&amp;gt; 20% was significantly (p=.000) associated with younger age, greater size, positive lymph nodes, poor grading, absent or low ER and/or PR expression level, HER-2 over-expression or amplification with or without co-expression of ER and/or PR, triple negative subtypes. Mib-1 was a significant predictor of worse DFS and OS (p=.000). At a median follow up of 32 months the DFS and OS were 97.4 and 99.2% respectively in Mib-1 ≤20% group and 92.4 and 97.2% respectively in Mib-1 &amp;gt; 20%. There were 195 relapses (7,3%): 139 (5.2%) in Mib-1 &amp;gt; 20% and 56 (2.1%) in Mib-1 ≤ 20%. Breast cancer related deaths were 74 (2.8%) with 58 (2.2%) in mib-1 &amp;gt; 20% group and 16 (0.6%) in mib-1 ≤ 20%.Mib1 &amp;gt;20% was predictive of poorer prognosis in &amp;gt; 40 years patients, small tumors (T1), lower grading (G1 and G2), positive ER and/or PR group with high or intermediate expression, negative HER-2 tumors. However, in Cox multivariate analysis mib-1 didn't maintain independent prognostic value.CONCLUSIONS: In our experience, Mib-1 confirms to be a significant prognostic biomarker for DFS and OS in early breast cancer. It could provide additional information beside other clinico-pathological parameters to perform the risk stratification of early breast cancer patients. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6054.
Abstract 4595: ERK/MAPK regulation of ERRγ in Tamoxifen resistant breast cancer
Authors: Mary M. Mazzotta, Minetta C. Liu, Robert Clarke, Rebecca B. Riggins
Journal: Cancer Research (2010)

Abstract Breast cancer is a serious public health problem that is the second-most common cause of cancer-related death in women. Endocrine therapy, like Tamoxifen (TAM), has made significant contributions to the successful management of ER+ breast cancer but unfortunately 30-50% of these tumors may acquire endocrine resistance. However, not all ER+ breast cancers are the same. Two of the major classifications of breast cancer are invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC). In comparison to IDC, a significantly greater percentage of ILCs are estrogen receptor alpha-positive (ER+) and progesterone receptor-positive (PR+). Therefore, women diagnosed with this tumor subtype should be ideal candidates for endocrine or antiestrogen therapy. However, clinical studies differ as to whether ILC patients experience better or worse survival following antiestrogen treatment when compared to ER+ IDC patients. In a model of TAM-resistance in ILC, we have shown that the orphan nuclear receptor estrogen related receptor gamma (ERRγ) plays a functional role in the resistant phenotype of LCCTam cells, ERRγ overexpression is sufficient to induce TAM resistance, and we show for the first time that ERRγ is serine-phosphorylated in TAM-resistant breast cancer cells in association with increased expression and activity of extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK; ERK). We have also recently found an IDC-derived model of TAM-resistance to overexpress ERRγ. Therefore, we hypothesize that ERK regulates ERRγ transcriptional activity and is a critical determinant of ERRγ-induced TAM resistance in breast cancer. To test this hypothesis, we used two antiestrogen-sensitive and -resistant breast cancer cell line pairs: IDC-derived RR cells and their sensitive controls MCF7, and the ILC-derived LCCTam cells and their sensitive controls SUM44. In both sensitive controls we found TAM alone to cause cell death. When we added the ERK inhibitor, U0126, to the TAM treatments, cell death increased. The resistant cell lines showed no effect with the addition of TAM alone, but the TAM treatment coupled with the inhibitor restored sensitivity and caused cell death. Additionally, we tested the transcriptional activity of ERRγ in the presence or absence of the ERK inhibitor. We found each of the four cell lines to show decreased ERRγ transcriptional activity in the presence of U0126. Future studies include the identification of the serine residues on ERRγ being phosphorylated by ERK, and whether ERRγ overexpression is associated with increased ERK expression and activity, poor overall survival, and poor response to TAM in breast cancer patients treated with endocrine therapy. 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 4595.
Genetic Defects and Clinical Characteristics of Patients with a Form of Oculocutaneous Albinism (Hermansky–Pudlak Syndrome)
Authors: W A Gahl, M Brantly, M I Kaiser-Kupfer, F Iwata, S Hazelwood, V Shotelersuk, L F Duffy, E M Kuehl, J Troendle, I Bernardini
Journal: New England Journal of Medicine (1998)

Hermansky–Pudlak syndrome is characterized by oculocutaneous albinism, a storage-pool deficiency, and lysosomal accumulation of ceroid lipofuscin, which causes pulmonary fibrosis and granulomatous colitis in some cases. All identified affected patients in northwest Puerto Rico are homozygous for a 16-bp duplication in exon 15 of a recently cloned gene, HPS. We compared the clinical and laboratory characteristics of these patients with those of patients without the 16-bp duplication.
Demonstration of Ventriculoperitoneal Shunt Infection on Ga-67 Citrate Scintigraphy
Authors: SHUNG-SHUNG SUN, FENG-JU CHUANG, KUO-LIANG CHIU, CHIA-HUNG KAO
Journal: Clinical Nuclear Medicine (2002)

SUN, SHUNG-SHUNG M.D.; CHUANG, FENG-JU M.D.; CHIU, KUO-LIANG M.D.; KAO, CHIA-HUNG M.D. Author Information
Abstract 4154: Intratumoral heterogeneity of HER2/neu expression in diffuse-gastric carcinoma of European patients and its relevance for patients’ management
Authors: Gorana Tomasic, Gabriel G. Malouf, Virginie Marty, David Malka, Philippe Vielh, Michel Ducreux, Valerie Boige
Journal: Cancer Research (2010)

Abstract Background: This study assessed the human epidermal growth factor receptor-2 (HER2) protein expression, its relationship with gene amplification and its intra-tumoral heterogeneity in diffuse-gastric carcinoma, a subset of gastric carcinoma that might benefit from Trastuzumab in case of HER2 amplification according to recently reported ToGA trial (J Clin Oncol 27:18s, 2009 (suppl; abstr LBA4509) Patients and methods: The study included 51 European consecutive patients who underwent surgical resection in our institution between January 1991 and December 2007 for diffuse gastric carcinoma. A tissue-microarray was constructed using paraffin-embedded tissues of gastrectomy and matched lymph nodes. HER2 were evaluated by immunohistochemistry (IHC), using the same criteria than for breast cancer. All samples with a 2+ or 3+ HER2 overexpression were evaluated by FISH. Results: HER2 overexpression was observed in 2 (4%) tumors and there was intratumoral heterogeneity. The first tumour shows 2+/3+ immunostaining in lymph nodes with negative immunostaining in the primary tumor. The second tumor shows a focal 3+ HER2 immunostaining in the primary tumor without evidence of positive immunostaining in lymph nodes and peritoneal metastasis. Using FISH, HER2 3+ tumour areas had a gene amplification, whereas no amplification was found in 2+ tumor. The 2 HER2 positive tumors showed the same heterogeneous pattern, with adjacent 3+ positive and negative areas by both IHC and FISH. There was a 100% concordance between TMA and the tissue-sections. Despite complete resection, the 2 patients with HER2 expression died within 15 months. Conclusions: This study showed that 4% of resected diffuse gastric carcinoma had a heterogeneous distribution of HER2 gene amplification. These findings raise the question whether HER2 testing should be realized systematically in these patients and whether Trastuzumab may benefit in tumours with heterogeneous HER2 expression. 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 4154.