tbuckley/cabot-search huggingface dataset:
Relationship between K-Ras mutational status and EGFR expression evaluated using Allred score in primary and metastatic colorectal cancer.
Authors: E. Melucci, S. Conti, M. G. Diodoro, A. Torsello, M. Zeuli, B. Casini, C. Ercolani, F. Cognetti, C. Garufi, M. Mottolese
Journal: Journal of Clinical Oncology (2010)

3568 Background: EGFR plays an important role in colorectal cancer (CRC) tumor progression and represents a natural target for molecular anticancer drugs. The monoclonal antibodies (MAbs) cetuximab and panitumumab, capable to inactivate the EGFR pathway, have entered in clinical practice for the treatment of metastatic CRC. While EGFR expression, detected by immunohistochemistry (IHC), is unable to predict response to molecular therapy, recent studies demonstrated that K-Ras status may be predictive of response to the MAbs. Methods: In this study we aimed to: 1. determine whether a correlation between K-Ras mutations and EGFR overexpression may occur, 2. verify whether K-Ras status may change during tumor progression. To this end in 414 CRC patients we evaluated K-Ras mutations using a direct cycle sequencing and EGFR expression using the Allred score which is a composite of the percentage of stained cells and the intensity of their staining. In 282 (68%) cases the analyses were performed in the primary tumor, in 67 (15%) in metastatic lesions and in 70 (17%) both in primary and in metastatic tumors. Results: we evidenced that 154 CRCs (37 %) were K-Ras mutated and 342 (82%) EGFR positive. In the 102 CRCs with EGFR negative or with a low Allred score (2-3) we found 65% of cases K-Ras mutated being mutated only 24% of the 73 CRCs with a high EGFR Allred score (7-8) (p = 0.0001). Moreover, we observed that 4 of 62 (6%) primary CRC and paired metastases showed changes in K-Ras mutational status. These cases did not vary in EGFR expression and did not show any differences concerning Loss of Heterozygosity (LOH) of CA Simple Sequence Repeat 1 (CASSRI) of intron 1 of EGFR. Conclusions: our data showed that CRC with K- Ras wild type consistently presents a high EGFR Allred score. Moreover, although K-Ras status varies between during progression in a small percentage of cases, a different response to monoclonal antibodies treatment may occur in these patients. Therefore, the characterization of the molecular profile in metastatic CRC has become increasingly important for targeted therapy selection. No significant financial relationships to disclose.
A synthetic peptide, PCK3145, for the treatment of hormone refractory prostate cancer
Authors: L. Daigneault, C. Panchal, H. I. Scher, S. F. Slovin, S. Rabbani, H. Dulude, S. Garde, M. Ruiz, J. Wu, R. Hawkins
Journal: Journal of Clinical Oncology (2005)

4654 Background: PCK3145 is a 15-mer synthetic peptide derived from Prostate Secretory Protein (PSP94). PSP94 is down regulated in advanced prostate cancer suggesting a role as survival mechanism for prostate cancer cells. PCK3145, as PSP94, demonstrated anti-tumor activities both in vivo and in vitro. Its underlying mechanism of action is thought to be by activation of receptor-mediated signal transduction pathways that cause apoptosis and normalize matrix metalloproteinase-9 (MMP-9) levels in the treated animals. Methods: Given the pre-clinical data in animal models suggesting that PCK3145 reduces prostate tumor growth, a dose-escalating study was conducted in 16 patients (pts) with metastatic hormone refractory prostate cancer (HRPC). Four cohorts of 4 pts received doses of 5, 20, 40 or 80 mg/m2. One cycle consisted of i.v. administration of PCK3145, three times per week for 4 weeks followed by a 7-day post-treatment period. Results: On the average, pts received two cycles although one pt received 5 cycles without adverse toxicity. The mean elimination half-life ranged from 0.354 to 1.45 hours with doses from 20 to 80 mg/m2. Mean Clearance appeared to increase with increasing dose level and the mean AUC values did not increase proportionally over the dose ranges studied. Pts remain under continued observations for PSA assessment and radiographic progression with 3 pts having stable disease for 2 cycles. Overall, 7 pts had stable disease and 7 pts had progressive disease at the time of finishing the study. One pt had a unconfirmed partial response. The biological activity of PCK3145 was monitored by assessing in patient blood samples, the level of MMP-9, MMP-2, TIMP-1, in addition to PSA, PAP, CEA, NSE, hCG. A substantial reduction in MMP-9 level was observed in 7 pts with elevated MMP-9 levels at baseline; 6 pts with low baseline MMP-9 levels (<100 μg/L) had no change after the first cycle. Conclusions: The mechanism of action of PCK3145 and its effect as a single agent and in combination with other therapeutic drugs to block cancer growth and skeletal metastasis is currently being evaluated. A Phase II trial is currently under development to explore the impact of PC3145 on MMP levels and in delaying time to radiographic progression. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Procyon Biopharma Procyon Biopharma Procyon Biopharma Procyon Biopharma
Temozolomide in the treatment of gynecological leiomyosarcoma: A Spanish Group for Research on Sarcomas (GEIS) study
Authors: X. Garcia Del Muro, J. Fra, J. Martinez Trufero, I. Sevilla, P. Escudero, J. Cruz, J. Martín, A. Casado, V. Arrazubi, J. M. Buesa
Journal: Journal of Clinical Oncology (2005)

9030 Background: Temozolomide (TMZ) administered as an extended continuous oral schedule showed promising activity in the subgroup of patients (pts) with gynecological leiomyosarcoma (LMS) in a prior phase II study on pretreated soft tissue sarcoma pts (Proc ASCO 2001; 1412). Based on these results, pts have been treated at our centers in a compassionate use program. The purpose of this study was to assess the activity of this schedule in a wider group of gynecologic LMS pts by combining all pts treated. Methods: Twenty-five pts with advanced gynecologic LMS were included in this retrospective study, 11 from a prior phase II trial and 14 from a compassionate use program cohort, treated in 8 centers from January 2000 to date. All them have non-irradiated measurable lesions. Pts received oral TMZ at doses of either 75 mg/m2/day (18 pts) or 100 mg/m2/day (9 pts) continuously for 6 weeks. Results: Median age was 58 (27–73) years; PS: 0:9, 1:12, 2:4 pts. Primary tumor sites were uterus (21), ovary (2 pts) and parametrium (1). Metastases were present in 23 pts. Twenty-three pts had progressed after doxorubicin-based therapy; 2 had no prior chemotherapy. A total of 54 cycles were administered (median 2, range 1–9). Hematological toxicity was: Neutropenia G-IV:1, G-II:6 pts, Thrombocytopenia G-IV:1, GII:1 pts, Anemia G-IV: 1, G-III:2, G-II:2 pts). Non-hematological toxicity was: Nausea G-III:1, G-II:10 pts, Vomiting G-III: 2, G-II:9 pts, Asthenia G-III:2, G II:4 pts, Stomatitis G-II:1 pt. One pt refused the treatment and was not evaluable for response. There were 2 CR, 6 PR, 1 SD and 15 PD, for an overall response rate of 32% (95% CI, 15–53%). Median response duration was 11.4 months (range 3.9–40). In 4 pts, response lasted >1 year. Median time to progression and median overall survival were 2.8 months (95% CI, 0.6–4.9) and 15.4 months (95% CI, 6.8–23.9), respectively. Progression free-rates at 3 and 6 months were 50% and 42%, respectively. Conclusions: TMZ at this extended continuous schedule is well tolerated and appears to have high activity against pretreated gynecologic LMS, producing in some pts long-lasting responses. Further evaluation through clinical trials is warranted. No significant financial relationships to disclose.
Antitumor activity of esorubicin in human tumor clonogenic assay with comparisons to doxorubicin.
Authors: S E Salmon, L Young, B Soehnlen, R Liu
Journal: Journal of Clinical Oncology (1984)

The new anthracycline analog, esorubicin (4'deoxy-doxorubicin, ESO), was tested against fresh biopsies of human solid tumors in vitro in clonogenic assay and the results were contrasted to those obtained with doxorubicin (DOX). ESO appeared to be significantly more potent on a weight basis than DOX in these studies, and exhibited a spectrum of antitumor activity in vitro that was in general qualitatively similar to that observed with DOX. In vitro antitumor activity was observed in a wide variety of human cancers including anthracycline-sensitive tumor types. ESO has previously been reported to have decreased cardiac toxicity in preclinical models as compared to DOX. Comparative testing of these anthracyclines on granulocyte-macrophage colony-forming units (GM-CFUs) and tumor colony forming units (TCFUs) indicated that the in vitro GM-CFU assay is more sensitive to these myelosuppressive drugs than are TCFUs, and underscores the need for in vivo studies to determine normal tissue toxicity and the therapeutic index of a drug. Early results of phase I studies suggest that with respect to myelosuppression, the maximally tolerated dose of ESO will be about half that of DOX. The increased in vitro antitumor potency observed for ESO and a spectrum of activity (even at one half the dose of DOX) supports the broad testing of ESO in the clinic to determine whether it will prove to be a more effective and less toxic anthracycline.
Anti-lactadherin antibodies in anti-angiogenic cancer therapy of breast cancer stem cells
Authors: A. A. Epenetos, G. Bower, M. Deonarain, L. Bonney
Journal: Journal of Clinical Oncology (2007)

14138 Background: Angiolix (Hu-Mc3) is a humanized monoclonal antibody that recognizes a migrating adhesion molecule called Lactadherin. This novel antibody has a high affinity for its antigen and recognizes an epitope on Lactadherin which interacts with the the ’RGD’- motif found on integrin receptors on newly formed endothelial cells. Lactadherin binding leads to signalling via a VEGF-independent integrin receptor signalling cascade leading to vascular endothelial cell profileration. Lactadherin binding may also increase the potency of VEGF-VEGF receptor signalling. Methods: We studied the expression of Lactadherin on breast cancer cell lines, the biodistribution of Angiolix in human breast cancer xeografts and its ability to inhibit tumor growth in vivo. Results: Our data show that tumor cells express lactadherin in vivo and that Angiolix could achieve more than 75% growth inhibition of human breast cancer growing as xenografts . Conclusions: In view of the recent finding that cancer stem cells can over-express the pro-angiogenic VEGF and make a major contribution to tumor vasculature proliferation leads to the possibility that Angiolix may be able to act to specifically target breast cancer stem cell and cause tumor regression by blocking the growth of tumor vasculature by its ability to neutralise Lactadherin-integrin receptor binding. [Table: see text]
Phase I and Pharmacologic Study of Oral Fluorouracil on a Chronic Daily Schedule in Combination With the Dihydropyrimidine Dehydrogenase Inactivator Eniluracil
Authors: Sharyn D. Baker, Robert B. Diasio, Seamus O’Reilly, V. Sol Lucas, Soo Peang Khor, Susan E. Sartorius, Ross C. Donehower, Louise B. Grochow, Thomas Spector, John A. Hohneker, Eric K. Rowinsky
Journal: Journal of Clinical Oncology (2000)

PURPOSE: To determine the maximum-tolerated dose (MTD), toxicities, and pharmacokinetics of oral fluorouracil (5-FU) administered twice daily in combination with oral eniluracil, an inactivator of dihydropyrimidine dehydrogenase, administered for 28 days every 35 days. PATIENTS AND METHODS: Oral 5-FU 1.35 mg/m 2 twice daily was administered with oral eniluracil 10 mg daily for 14 to 28 days, followed by a 1-week rest period. Eniluracil was started 1 day before 5-FU. Patients then received escalated doses of oral 5-FU 1.35 to 1.8 mg/m 2 twice daily with an increased dose of eniluracil 10 mg twice daily for 28 days. A reduced dose of 5-FU 1.0 mg/m 2 with eniluracil 20 mg twice daily was evaluated. RESULTS: Thirty-six patients with solid malignancies were enrolled onto the study. Diarrhea was the principal dose-limiting toxicity of oral 5-FU and eniluracil given on this chronic schedule. The recommended phase II dose is 5-FU 1.0 mg/m 2 twice daily with eniluracil 20 mg twice daily. Mean (SD) values for terminal half-life, apparent volume of distribution, and systemic clearance of 4.5 hours (0.83 hours), 19 L/m 2 (3.0 L/m 2 ), and 51 mL/min/m 2 (13 mL/min/m 2 ), respectively. An average of 77% of 5-FU was excreted unchanged in urine after 28 days of treatment. The mean (range) 5-FU C SS,min values achieved at the 1.0 mg/m 2 dose level were 22 ng/mL (8 to 38 ng/mL). CONCLUSION: Chronic oral administration of 5-FU with oral eniluracil is tolerable and produces 5-FU steady-state concentrations similar to those achieved with protracted intravenous administration of 5-FU on clinically relevant dose schedules. Eniluracil provides an attractive means of administering 5-FU on protracted schedules.
CD146 in the pathogenesis of COPD
Authors: Adelheid Kratzer, Jonas Salys, Hong Wei Chu, Martin Zamora, Laima Taraseviciene-Stewart
Journal: European Respiratory Journal (2011)

Background:  Chronic obstructive lung diseases (COPD) are the major cause of death and disability worldwide. The major risk factor for COPD is tobacco smoke. Cell adhesion molecule CD146 is expressed in all types of human endothelial cells (EC) and exists in a membrane-anchored and a soluble form (sCD146). The plasma concentration of sCD146 is modulated in inflammatory diseases associated with endothelial alterations.   Aims and objectives:  To investigate the role of endothelial CD146 in the pathogenesis of cigarette smoke (CS)-induced emphysema.   Methods:  Sprague Dawley rats were exposed to second hand CS for two months. The lung tissue and bronchoalveolar lavage (BAL) cells were examined for CD146 gene and protein expression and emphysema development as measured by MLI. sCD146 levels were determined in circulation and BAL fluid in rats and in patients with COPD. CD146 expression and function was also examined in rat pulmonary EC exposed to CS in vitro.   Results:  Sprague Dawley rats exposed to cigarette smoke for 2 months developed significant emphysematous changes (as measured by mean linear intercept) and had increased levels of circulating and bronchoalveolar lavage fluid sCD146. Treatment of rat pulmonary EC with cigarette smoke extract in vitro also resulted in a decreased membrane-bound CD146 expression and increased sCD146 levels in the medium. Moreover, circulating levels of sCD146 were significantly increased in serum of patients with COPD and correlated with the disease severity.   Conclusion:  Our data indicate that CD146 is involved in CS-induced vascular dysfunction and that sCD146 can be a candidate marker for COPD/emphysema.  Funded by AHA 0735388N, FAMRI CIA 072053, Emphysema Research Fund and Bixler Family Foundation.
Unilateral versus bilateral breast cancers, synchronous versus non-synchronous bilateral breast cancers: Results of a long survey (25 years) concerning 3632 patient
Authors: M. Namer
Journal: Journal of Clinical Oncology (2004)

729 Background: At the Antoine Lacassagne center, in Nice, France, between 1977 and 2001, 3336 unilateral breast cancers (UBC) and 298 bilateral breast cancers (BBC) were treated by surgery. This study was leaded to evaluate prognostic of UBC and BBC. Methods: BBC were divided in two groups: synchronous bilateral breast cancers (SBBC) is defined by cancer in each breast either simultaneously or within a 6 months interval and non-synchronous bilateral breast cancer (NSBBC) is defined by controlateral breast cancer over 6 months after the first cancer. Aim of this study is to compare UBC with BBC population and to compare the 103 SBBC with the 195 NSBBC. Results: Comparison of prognosis features of UBC and BBC population: there was no difference regarding median age, menopausal status, tumor size, histological nodal invasion and in situ carcinoma's presence. Nevertheless, we noticed more histological SBR grade III (p=0.055) and more estrogen receptor negative (p=0.02) in UBC group. Therapeutic patterns, as conservative surgery, radiotherapy and adjuvant chemotherapy, were equally distributed between these two populations. No significant difference was noticed regarding overall survival. Comparison of SBBC and NSBBC: SBBC population was older (p=0.001) and presented more histological nodes involvement (52 % vs 26 %; p=0.001) receiving thus more frequently adjuvant hormonotherapy (p=0.001) and chemotherapy (p=0,04). There was no difference in term of tumor size, histological grade, histological type, in situ carcinoma's presence, estrogen and progesterone receptors. The NSBBC population had a better overall survival than the SBBC ones (p=0.007). Conclusions: BBC have the same features and the same outcomes than UBC. They do not require more aggressive treatment. SBBC have a poorer prognosis than NSBBC due to a more frequent axillary nodes involvement. As patients were older, they received more often adjuvant hormonotherapy. No significant financial relationships to disclose.
Abstract 15047: Aortic Neck Length and Mortality After Repair of Ruptured Abdominal Aortic Aneurysm
Authors: Janet T Powell
Journal: Circulation (2014)

Introduction:  Aneurysm morphology indicates whether a patient with ruptured abdominal aortic aneurysm (rAAA) is eligible for endovascular aneurysm repair (EVAR) and may influence the outcome of both EVAR and open surgical repair. In the emergency setting, the morphological criteria for EVAR (IFU, instructions for use) may be relaxed, but by how much?   Hypothesis:  aneurysm morphology influences mortality from rAAA repair.   Methods:  Patients randomised to either an endovascular strategy or open repair in the IMPROVE trial (ISRCTN48334791), with a proven diagnosis of rAAA, who underwent repair and with admission CT scan sent to the core laboratory, were included in this analysis of 30-day mortality and re-interventions, according to a pre-specified plan, focusing on IFU and 6 morphological variables: maximum aortic diameter, neck diameter, neck length, proximal neck angle, neck conicality & maximum common iliac diameter.   Results:  458 patients (364 men), mean age 76 years were included, with EVAR commenced in 177 and open repair in 281 cases, with 155 deaths and 88 re-interventions. The mean maximum aortic diameter was 8.6cm. There were no important correlations between the 6 morphological variables. Patients within IFU (58%) had lower mortality, adjusted* OR 0.64 [95%CI 0.41,1.01]. Only aortic neck length (mean(SD), 23.2(16)mm) was associated significantly (inversely) with mortality, particularly for open repair: overall mortality reduced for each SD increase in length, adjusted** OR 0.72 [95%CI 0.56,0.91]. With fewer re-interventions, only iliac diameter showed a borderline association.   Conclusions:  Short aneurysm necks preclude EVAR and strongly adversely influence mortality after open repair of rAAA. This is an important reason why observational studies, but not randomised trials, have shown an early survival benefit for EVAR.  *(**) for age, sex, Hardman index, blood pressure and randomised group (and other morphological variables).
Combination chemotherapy with tetracycline and aggressive supportive care for immunoproliferative small-intestinal disease lymphoma.
Authors: N S el Saghir
Journal: Journal of Clinical Oncology (1995)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1995.13.3.794 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 7884437 Combination chemotherapy with tetracycline and aggressive supportive care for immunoproliferative small-intestinal disease lymphoma. N S el SaghirxN S el SaghirSearch for articles by this author https://doi.org/10.1200/JCO.1995.13.3.794 PDF "Combination chemotherapy with tetracycline and aggressive supportive care for immunoproliferative small-intestinal disease lymphoma.." Journal of Clinical Oncology, 13(3), pp. 794–795© 1995 by American Society of Clinical Oncology
Let's get tough on politicians
Authors: Roger L Weeks
Journal: BMJ (2007)

We select the letters for these pages from the rapid responses posted on bmj.com favouring those received within five days of publication of the article to which they refer.Letters are thus an early selection of rapid responses on a particular topic.Readers should consult the website for the full list of responses and any authors' replies, which usually arrive after our selection. DeciDing on caesarean section Vaginal birth after a caesarean is not always beneficialThe study by Montgomery et al and the accompanying editorial are based on the premise that vaginal delivery after one caesarean section is necessarily a beneficial and desirable objective or outcome. 1 2 However, the box shows the risks and benefits as published in the recent RCOG (Royal College of Obstetricians and Gynaecologists) guidelines. 3 Given that most women in developed countries are unlikely to have more than two to three babies, the value of promoting vaginal delivery after one caesarean section is highly questionable.Women with a breech presentation are no longer offered a choice between vaginal delivery and caesarean section on the basis of the results of the term breech trial. 4 Must we wait for such a trial to recognise that vaginal delivery after one caesarean section costs lives and caesarean section saves lives?Women should have a choice, but this should not come before safety.To promote a process that is known to be associated with greater mortality and morbidity, or consider such a process as beneficial or desirable seems inappropriate irrespective of the reduction in women's anxiety.
Truncating Erythropoietin Receptor Rearrangements in Acute Lymphoblastic Leukemia
Authors: Ilaria Iacobucci, Yongjin Li, Kathryn G. Roberts, Stephanie M. Dobson, Jaeseung C. Kim, Debbie Payne-Turner, Richard C. Harvey, Marcus Valentine, Kelly McCastlain, John Easton, Donald Yergeau, Laura J. Janke, Ying Shao, I-Ming L. Chen, Michael Rusch, Sasan Zandi, Steven M. Kornblau, Marina Konopleva, Elias Jabbour, Elisabeth M. Paietta, Jacob M. Rowe, Ching-Hon Pui, Julie Gastier-Foster, Zhaohui Gu, Shalini Reshmi, Mignon L. Loh, Janis Racevskis, Martin S. Tallman, Peter H. Wiernik, Mark R. Litzow, Cheryl L. Willman, John D. McPherson, James R. Downing, Jinghui Zhang, John E. Dick, Stephen P. Hunger, Charles G. Mullighan
Journal: Cancer Cell (2016)
Human Metapneumovirus and Lower Respiratory Tract Disease in Children
Authors: Nicola Principi, Susanna Esposito, Samantha Bosis
Journal: New England Journal of Medicine (2004)

Human Metapneumovirus and Lower Respiratory Tract Disease in Childrento the editor: The case definition of croup given by Williams et al. in their study of metapneumovirus (Jan.29 issue) 1 seems misleading.The authors state that croup is an "acute lower respiratory tract infection characterized by hoarseness, cough, and stridor."On the contrary, croup is classified as an acute upper-airway disease in several textbooks of pediatrics. [2]3][4] Recognizing croup as an important cause of acute upper-airway obstruction and its pertinent features, as distinct from life-threatening bacterial epiglottitis, is the classic point made in medical teaching worldwide.
India has world’s highest number of stillbirths
Authors: Sanjeet Bagcchi
Journal: BMJ (2016)

India had the highest number of stillbirths and neonatal deaths in the world in 2015, says a study in the Lancet .1

Last year there were an estimated 592 100 stillbirths and 695 900 neonatal deaths in India. Nigeria had the second highest number of stillbirths, with 313 700, and third was Pakistan (242 600). Pakistan had the second highest number of neonatal deaths (244 700), followed by Nigeria (240 100).

Researchers looked at the number of stillbirths per 1000 births in 157 countries and found that nearly 2.6 million babies around the globe died in …