tbuckley/cabot-search huggingface dataset:
Clinical and pathologic correlation of <i>p73</i> expression in surgically staged endometrial cancer
Authors: K. E. Resnick, A. Suarez, C. Nagel, D. Cohn, D. O'Malley
Journal: Journal of Clinical Oncology (2009)

e22153 Background: p73 is a p53 homologue that has been implicated both as a tumor suppressor and oncogene. While known to play a role in the apoptotic response, homozygous p73 knockout mice have not shown an increased susceptibility to tumor formation. However, recent literature suggests that p73 dysregulation may play a role in retinoblastoma, ovarian and bladder cancer. We sought to correlate p73 status with clinical-pathologic factors including mismatch repair status, in a large cohort of comprehensively staged endometrial cancers. Methods: Primary endometrial and colon cancers were used to create a tissue microarray (TMA). Two-hundred eight endometrial specimens were available for evaluation. Immunohistochemistry with p73 was performed using commercial available antibodies. Positive staining was defined as &gt; 10% cells having positive nuclear staining. Microsatellite (MSI) instability testing as well as IHC for p53 had been previously performed. Statistical analysis was performed using Fisher's exact test. Results: In six non-neoplastic control endometrial samples examined, p73 appears to stain mainly surface epithelial cell nuclei and superficial glands. p73 expression was identified in 71 (34%) of endometrial cancer specimens. There was no correlation between p73 status and histology, stage, grade or MSI status. Strong correlation that was noted between p53 status and p73 status. Ninety-eight (71%) of the 137 p73 negative tumors were noted to be wildtype(negative staining) for p53 (p&lt;.001). However, when the (-)p73 (+)p53 and (+) p73 (+)p53 phenotypes were examined separately, there was no correlation with stage or grade. Conclusions: p73 is a p53 homologue with uncertain potential as an oncogene and tumor suppressor gene. To date, we offer the largest study of p73 expression in comprehensively staged endometrial cancer. While we show significant loss of p73 expression among cancer specimens, we were unable to demonstrate a relationship between p73 and clinical factors. However, an interesting correlation between p53 status and p73 does appear. The potential role for p73 and p53 in the apoptotic response to cytotoxic chemotherapy is interesting and deserves further study. No significant financial relationships to disclose.
Neoplastic Transformation of Fetal Rat Brain Cells in Culture After Exposure to Ethylnitrosourea In Vivo23
Authors: O. D. Laerum, M. F. Rajewsky
Journal: JNCI Journal of the National Cancer Institute (1975)

A single, transplacental pulse of N-ethyl-N-nitrosourea (ENU; 75 µg body wt) to the fetal (18th day of gestation) BD IX rat led to death with malignant tumors of the central and peripheral nervous system after a median time of ≈195 days. In contrast to untreated control cells, dissociated brain cells transferred to long-term cell culture 20–90 hours after the ENU pulse became tumorigenic after ≈200 days, as assayed byreimplantation into baby BD IX rats. This was preceded by a characteristic sequence of phenotypic alterations (termed “stages I-IV”). During early primary culture (stage I), both ENU and control cultures exhibited stationary glia-like cells on a growing layer of epithelioid (possibly glia precursors) and few fibroblast-like cells. Stage II (≈10th-40th day) was characterized by a constant proportion of glia-like cells in the ENU cultures and by their disappearance in the controls. During stage III (≈40th-100th day), slowly proliferating glia-like cells in the ENU cultures formed “piled-up” foci. They could then be removed from the underlying cell layer and cultured separately. Transition to stage IV (≈100th–200th day) was marked by proliferation of morphologically altered cells, which subsequently acquired the capacity to form colonies in semisolid agar and finally became tumorigenic (stage V). This system may represent a model for the study of malignant transformation.
Optimal Needle Length of Epinephrine Prefilled Syringe in Thai Infants
Authors: Buntita Bamrungchaowkasem, Wiparat Manuyakorn, Nichanun Ruangwattanapaisarn, Suwat Benjaponpitak, Wasu Kamchaisatian
Journal: Journal of Allergy and Clinical Immunology (2016)
A phase II study of amplitude-modulated electromagnetic fields in the treatment of advanced hepatocellular carcinoma (HCC)
Authors: F. Costa, A. C. de Oliveira, R. Meirelles, T. Zanesco, R. Surjan, M. Chammas, A. Barbault, B. Pasche
Journal: Journal of Clinical Oncology (2007)

15155 Background: Phase I data show that low levels of electromagnetic fields modulated at specific frequencies administered intrabucally with the THERABIONIC device are a safe and potentially effective treatment for advanced cancer. The device emits a 27.12 MHz radiofrequency signal, amplitude-modulated at tumor-specific frequencies ranging from 0.2 to 23,000 Hz. The device is connected to a spoon- like coupler placed in the patient’s mouth during treatment. Patients with advanced HCC and limited therapeutic options were offered treatment with HCC-specific frequencies. Methods: From October 2005 to October 2006, 38 patients with advanced HCC were recruited in a phase II study. The patients received three daily 40 min treatments until disease progression or death. The median age was 64.0 ± 14.2 years. 32 patients were male and 29 patients had documented progression of disease (POD) by IV contrast imaging prior to study entry. 8 patients had not received prior therapy because of metastases (3), poor medical condition (3), declined chemotherapy (2). Results: As of January 2007, 12 patients are still on therapy, 20 patients died of tumor progression, 2 patients are lost to follow-up and 3 patients withdrew consent. 27 patients are eligible for response. The overall objective response rate as defined by partial response (PR) or stable disease (SD) in patients with prior documented POD was 31.6%: 3 PR and 9 SD. The median survival was 20.7 weeks with a median duration of therapy of 17.5 weeks. 13 patients have received therapy for more than six months. The median duration of response is 12.9 weeks. 12 patients reported pain at study entry: 8 of them (66%) experienced decreased pain during treatment. There were no NCI grade 2/3/4 toxicities. One patient had grade 1 mucositis and grade 1 fatigue. Conclusion: In patients with advanced HCC, THERABIONIC is a safe and effective novel therapeutic option, which has significant anti-tumor effect and provides pain relief in the majority of patients. [Table: see text] No significant financial relationships to disclose.
Abstract 14660: A Nanomedicine-Based Treatment Regimen to Induce Plaque Remodeling to a Favorable Phenotype in Mice With Advanced Atherosclerosis
Authors: Jun Tang, Mark E Lobatto, Wei leong, Hendrik Sager, Susanne E van der Staay, Sarian M van Rijs, Sarayu Ramachandran, Yaritzy M Astudillo, Raphael Duivenvoorden, Ying Wang, Ira Tabas, Valentin Fuster, Matthias Nahrendorf, David P Cormode, Edward A Fisher, Zahi A Fayad, Willem J Mulder
Journal: Circulation (2013)

Rationale: Inflammatory macrophages contribute to an increased chance of atherosclerotic plaque rupture. Previously, we developed a simvastatin loaded high-density lipoprotein ([S]-rHDL) nanopartic...
IMmunologic and Ultrastructural Heterogeneity of Acute Lymphoblastic Leukemia-Associated Antigen-Positive Human Leukemias&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;, &lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;
Authors: T W LeBien, J L Parkin, R D Brunning, J H Kersey
Journal: JNCI Journal of the National Cancer Institute (1980)

To further examine the heterogeneity of human acute lymphoblastic leukemia, an immunologic and ultrastructural study was undertaken on 14 patients positive for the acute lymphoblastic leukemia-associated antigen (ALLA). In malignant cells from 7 of the patients studied, cytoplasmic granular inclusions that resembled those seen in leukemia mast cells and basophils (M-B granules) were evident. Four patients had malignant cells expressing the pre-B-cell phenotype (i.e., cytoplasmic IgM-positive and surface immunoglobulin-negative), and 3 patients had malignant cells that lacked both M-B granules and cytoplasmic IgM. These results support the existence of distinct phenotypic subgroups within the ALLA+ leukemias
Preclinical and clinical investigation of histone deacetylase inhibitor valproic acid given orally in androgen independent prostate cancer
Authors: S. Sharma, N. Vogelzang, B. Wong, C. Adams, P. Manno, K. Welborne, Y. Giraud
Journal: Journal of Clinical Oncology (2006)

14614 Background: Considerable preclinical data suggests that histone deacetylase inhibitors (HDAIs) can cause differentiation and apoptosis of prostate cancer cell lines and inhibit prostate cancer xenografts in vivo. There is evidence that valproic acid (VPA) is a HDAI and can be administered safely to cancer patients intravenously (Atmaca et al J Clin Oncol 2004). Methods: In the current investigation, 6 cell lines of a variety of solid tumors including prostate cancers were treated with escalating concentrations of VPA (0.5, 1, 2 and 4 mM) over 24–144 hours. Cell growth inhibition was studied by a modified MTS assay. Simultaneously, patients with androgen independent prostate cancers were treated with dose escalations of oral VPA every week or as tolerated (10, 15, 20, 25 mg/kg). Weekly total and free serum VPA, PSA and serum testosterone levels were obtained. In addition, lymphocytes were collected for histone H3 acetylation. Results: VPA inhibited all solid tumor cell lines in a dose-dependent and time-dependent fashion. Optimal (&gt;50% over control) inhibition of most cell lines required 2–4 mM exposure over at least 72–96 hours. Prostate and lung cancer lines were more sensitive to inhibition after VPA administration. A total of 5 patients (Median age 71, Range 48–78) were treated with VPA. Major adverse events included Gr 1 confusion (1 pt), Gr 1 fatigue (3 pts), Gr 1 Dizziness (2 patients) and Gr 1 nausea and vomiting (1 pt). When PSA levels were normalized for simultaneously drawn serum testosterone (Median 20, Range 16–281 ng/dl), all patients had transient drops in PSA. In 3 of 4 evaluable patients, normalized PSA increased after patients were discontinued from VPA because of side effects or co-morbid conditions. In 1 patient, normalized PSA declined after re-challenge with VPA. Conclusions: In this study, VPA has demonstrable activity in cell lines and in patients as measured by lowered PSA levels. Normalization of PSA to serum testosterone might be important to detect clinical effects of HDAIs. Updated clinical data and a correlation between PSA, serum levels of VPA and histone acetylation will be presented. No significant financial relationships to disclose.
MNGO-02GANODERIC ACID (A AND DM) INDUCED NDRG2 OVEREXPRESSION INHIBITS TUMORGENIC POTENTIAL OF MALIGNANT MENINGIOMA CELLS
Authors: Arabinda Das, Vikram Samant, Michele L. Decandio, Scott M. Lindhorst, Jerry Jaboin, William A. Vadergrift, Naren L. Banik, Pierre Giglio, Abhay K. Varma, Jeffery J. Raizer, Sunil J. Patel
Journal: Neuro-Oncology (2015)

Meningiomas are the second most common brain tumor, with a small proportion of these tumors being atypical or malignant. The aggressive subtypes are characterized by a capacity for invasion of normal brain with frequent recurrence patterns. Effective local therapies include surgery and radiation, but novel target specific drugs are needed to improve survival and reduce morbidity patients with for malignant anaplastic meningiomas (WHO Grade III) patients. Recently, an identified N-myc downstream-regulated gene 2 (NDRG2) protein was shown to be consistently down-regulated in grade III meningioma, demonstrating its role in tumorigenesis. In order to overexpress the tumor suppressor gene NDRG2 that inhibits tumorgenic pathways and proliferation of meningiomas, we used two bioactive triterpene compounds derived from Ganoderma lucidum (ganoderic acid A and ganoderic acid DM) in a preclinical meningioma model. Our in vitro and in vivo experiments demonstrated that overexpression of NDRG2 by the novel agents ganoderic acid (A/DM) inhibits proliferation, invasion and suppressed metastatic potential of high grade meningioma tumor growth via NDRG2 modulation of intracellular signals pathways while preserving normal brain tissue. Our results strongly demonstrate the effect of the novel agent ganoderic acid (A/ DM) on NDRG2 tumorigenesis establishing their translational potential for the treatment of patients with aggressive malignant meningiomas.
Inequalities in use of total hip arthroplasty for hip fracture: population based study
Authors: Daniel C Perry, David Metcalfe, Xavier L Griffin, Matthew L Costa
Journal: BMJ (2016)

<b>Objectives</b>&nbsp;To determine whether the use of total hip arthroplasty (THA) among individuals with a displaced intracapsular fracture of the femoral neck is based on national guidelines or if there are systematic inequalities. <b>Design</b>&nbsp;Observational cohort study using the National Hip Fracture Database (NHFD). <b>Setting</b>&nbsp;All hospitals that treat adults with hip fractures in England, Wales, and Northern Ireland. <b>Participants</b>&nbsp;Patients within the national database (all aged ≥60) who received operative treatment for a non-pathological displaced intracapsular hip fracture from 1 July 2011 to 31 April 2015. <b>Main outcome measures</b>&nbsp;Provision of THA to patients considered eligible under criteria published by the National Institute for Health and Care Excellence (NICE). <b>Results</b>&nbsp;114 119 patients with hip fracture were included, 11 683 (10.2%) of whom underwent THA. Of those who satisfied the NICE criteria, 32% (6780)<b></b>received a THA. Of patients who underwent THA, 42% (4903) did not satisfy the NICE criteria. A recursive partitioning algorithm found that the NICE eligibility criteria did not optimally explain which patients underwent THA. A model with superior explanatory power drew distinctions that are not supported by NICE, which were an age cut off at 76 and a different ambulation cut off. Among patients who satisfied the NICE eligibility, the use of THA was less likely with higher age (odds ratio 0.88, 95% confidence interval 0.87 to 0.88), worsening abbreviated mental test scores (0.49 (0.41 to 0.58) for normal cognition <i>v</i> borderline cognitive impairment)), worsening American Society of Anesthesiologists score (0.74, 0.66 to 0.84), male sex (0.85, 0.77 to 0.93), worsening ambulatory status (0.32, 0.28 to 0.35 for walking with a stick <i>v</i> independent ambulation), and fifths of worsening socioeconomic area deprivation (0.76 (0.66 to 0.88) for least <i>v</i> most deprived fifth). Patients receiving treatment during the working week were more likely to receive THA than at the weekend (0.90, 0.83 to 0.98). <b>Conclusions</b>&nbsp;There are wide disparities in the use of THA among individuals with hip fractures, and compliance with NICE guidance is poor. Patients with higher levels of socioeconomic deprivation and those who require surgery at the weekend were less likely to receive THA. Inconsistent compliance with NICE recommendations means that the optimal treatment for older adults with hip fractures can depend on where and when they present to hospital.
Irinotecan plus S-1 (IRIS) versus S-1 alone as first line treatment for advanced gastric cancer: Preliminary results of a randomized phase III study (GC0301/TOP-002)
Authors: K. Chin, H. Iishi, H. Imamura, O. Kobayashi, H. Imamoto, T. Esaki, M. Kato, Y. Tanaka, H. Furukawa
Journal: Journal of Clinical Oncology (2007)

4525 Background: Irinotecan has single agent activity and combination activity with S-1 reportedly in phase I/II studies with advanced gastric cancer patients (pts). S-1, oral fluoropyrimidine, also has activity on gastric cancer. A multicenter, randomized phase III trial comparing IRIS to S-1 alone in advanced gastric cancer was conducted. Methods: Pts with previously untreated gastric cancer were randomized to Arm A (oral S-1 80 mg/m 2 /day from day 1 to 28 followed by a 14-day rest period), or Arm B (oral S-1 80 mg/m 2 /day from day 1 to 21 and intravenous irinotecan 80 mg/m 2 on days 1 and 15 followed by a 14-day rest). Treatment was continued unless disease progression was observed. Inclusion criteria: PS (ECOG) of 0 to 2; adequate major organ functions. Primary endpoint was overall survival. Results: From June 2004 to November 2005, 326 pts were randomized to arm A (162 pts) and arm B (164 pts). Pts characteristics (arm A vs. arm B) were as follows: median age: 63 vs. 63 years, PS 0–1: 97% vs. 97%, and distribution of subtype of intestinal/diffuse/others: 44%/55%/1% vs. 41%/58%/1%. Among 187 RECIST-evaluable pts (93 vs 94) reviewed by independent review panel, best response rates were 26.9% for arm A and 41.5% for arm B(p=0.035). Among 319 toxicity-evaluable patients (161 vs 158), grade 3 or 4 toxicities for arm A vs arm B (% of pts) were as follows: neutropenia 9.3% vs 26.6%, diarrhea 5.6% vs 15.8%, anorexia 9.9% vs 15.8%, nausea 3.7% vs 7.0%, vomiting 0.6% vs 2.5%. Conclusions: IRIS is effective, and well tolerated in pts with advanced gastric cancer. Survival analysis is underway. No significant financial relationships to disclose.
Improved clinical response from neoadjuvant taxane chemotherapy across breast cancer subtypes
Authors: E. O. Jenkins, A. M. Deal, E. Burrows, A. Drobish, L. A. Carey
Journal: Journal of Clinical Oncology (2009)

576 Background: Adjuvant trials suggest that taxane (T) after doxorubicin and cyclophosphamide (AC) has little benefit in hormone receptor positive (HR+) patients compared to hormone receptor negative (HR-) patients, particularly if HER2 negative. Primary chemotherapy sensitivity is best determined from the neoadjuvant setting, therefore we sought to determine if HR+ primary tumors are less sensitive to taxane chemotherapy than HR- tumors. Methods: Clinical stage II-III breast cancer patients from the UNC Neoadjuvant Database who received sequential AC and T chemotherapy were evaluated. Clinical and radiographic responses were determined after AC and again after T allowing intrapatient sensitivity comparison, and included RECIST-defined complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). Hormone receptor status was determined at diagnosis, and subtypes included ER or PR positive, HER2 negative (HR+), ER and PR negative, HER2 positive (HER2+/ER-), and ER, PR and HER2 negative (TN). The ER or PR+, HER2+ group was too small for analysis. Patients who received neoadjuvant trastuzumab were excluded. Relationships of subtype and clinical response to AC and to T were assessed using Fisher's exact test. Results: 157 patients received neoadjuvant AC sequentially followed by T and were eligible for analysis. The majority of TN patients had PR to AC (56%), while the majority of HR+ patients had SD (54%). Of those with measurable disease after AC (n=127), a higher proportion of TN and HER2+/ER- patients had CR to T (43% and 45%, respectively) than HR+ patients (13%, p = 0.008 and p = 0.0393, respectively). While the majority of HR+ patients again had SD (52%), 42% responded to T. Conclusions: Our data suggests that TN and HER2+/ER- patients benefit more from neoadjuvant taxane chemotherapy than HR+ patients, however HR+ patients clearly derived benefit from T administered after AC. [Table: see text] No significant financial relationships to disclose.
A solution to small samples: A method validation study for sputum assay
Authors: Matthew Butler, William Monteiro, Lucy Marshall, Erol Gaillard
Journal: European Respiratory Journal (2014)

Background:  Induced sputum differential leukocyte counts as a relatively non-invasive and repeatable measure of airway inflammation have been used to phenotype patients with asthma. However, the current gold standard processing method (1) is not suitable for sputum plugs    Aim:  To compare our modified (small sample) sputum processing method (Method B) with the current gold standard (Method A).   Methods:  Sputum samples of sufficient quantity from 13 asthmatic patients (age-range 18-68years) were processed simultaneously using both methods. The median sample size used for Method B was 52mg (range 19-82) of sputum plugs. The difference in eosinophil %age between the methods was plotted against the mean result as proposed by Bland  et al.  (2).   Results:  The median %age eosinophils obtained using Method A was 4.75% (range 1.0-37.0) and 3.5% (range 0.5-32.6) using Method B. This difference was not statistically significant. There was no evidence of a systematic error. The bias and precision are shown in  Figure 1 .   Conclusions:  Our modified method for small samples gives similar results to the gold standard method described. This technique is particularly useful for paediatric studies.  References:  1) Pavord, I.  et al . Thorax 1997; 52:498  2) Bland, J. M.  et al . Stat Methods Med Res 1999; 8:135.
Adjuvant paclitaxel, capecitabine, and trastuzumab for HER-positive breast cancer
Authors: H. Jouhadi, A. Benider
Journal: Journal of Clinical Oncology (2009)

e11526 Background: Anthracyclines are integral components of most adjuvant chemotherapy regimens for surgically removed early breast cancer and are central to the accepted treatment standards. Recently the standard anthracycline regimen of doxorubicin plus cyclophosphamide was found to be inferior in preventing recurrence of breast cancer when compared to cyclophosphamide and docetaxel, questioning the necessity to expose patients to the potential cardiotoxicity of anthracycline in the adjuvant setting. Trastuzumab, cornerstone of treatment of breast cancers that overexpress HER2 produces Unfortunately, in combination with anthracyclines a high incidence of cardiotoxicity as seen in early trials of metastatic breast cancer. The trastuzumab adjuvant trial 006 from the Breast Cancer International Research Group shows for the first time that a nonanthracycline-containing regimen with trastuzumab has equivalent efficacy in decreasing the recurrence of breast cancer, with less incidence of cardiotoxicity when compared to anthracycline-containing trastuzumab adjuvant regimens. Methods: Our trial compared two adjuvant schemas of adjuvant chemotherapy arm1: paclitaxel(day 1-day 21: 6 courses), capecitabine(day1 to day 14: 6 courses) and trastuzumab (day 1 to day 21 for one year). Arm2: 4AC plus 4 TH plus trastuzumab for one year. Inclusion criteria: HER positive invasive ductal carcinoma, no lymphe node invaded at axillary dissection and no metatstasis, Negative ER and PR receptors Goal of study: evaluate efficacy and cardiac toxicity Results: From 2004 to 2005: 30 patient were included in each arm. After 3 years: DFS was respectively 93% in first arm and 90% in Second arm Four women developed severe cardiac toxicity in arm 2 versus no one in arm1 Conclusions: There is no difference in efficacy between the two arms but a significant increase in cardiac toxicity in the second arm. No significant financial relationships to disclose.