tbuckley/cabot-search huggingface dataset:
Massachusetts Medical Society
Authors: John Figgis Jewett
Journal: New England Journal of Medicine (1976)

An obese 41-year-old gravida 9, para 6, died 35 hours post partum during attempted endotracheal intubation for anesthesia.Having borne one set of twins and known for a year to be hypertensive, at 15 weeks the patient applied for prenatal care at a satellite clinic. The blood pressure was 190/110 mm Hg, the weight 121.4 kg, stature short, urinalysis negative, hematocrit 40 per cent, and random blood glucose level 124 mg per 100 ml. After two visits at two-week intervals, hospital admission was advised but refused. She then attended the clinic faithfully every week for a total of 18 visits. . . .
The First-in-class Anti-EGFR Antibody Mixture Sym004 Overcomes Cetuximab Resistance Mediated by EGFR Extracellular Domain Mutations in Colorectal Cancer
Authors: Francisco J. Sánchez-Martín, Beatriz Bellosillo, Mariona Gelabert-Baldrich, Alba Dalmases, Israel Cañadas, Joana Vidal, Alejandro Martinez, Guillem Argilés, Giulia Siravegna, Sabrina Arena, Klaus Koefoed, Laura Visa, Oriol Arpí, Ivan David Horak, Mar Iglesias, Christopher Stroh, Michael Kragh, Ana Rovira, Joan Albanell, Josep Tabernero, Alberto Bardelli, Clara Montagut
Journal: Clinical Cancer Research (2016)

Approved anti-EGFR antibodies cetuximab and panitumumab provide significant clinical benefit in patients with metastatic colorectal cancer (MCRC). However, patients ultimately develop disease progression, often driven by acquisition of mutations in the extracellular domain (ECD) of EGFR. Sym004 is a novel 1:1 mixture of two nonoverlapping anti-EGFR mAbs that recently showed promising clinical activity in a phase I trial in MCRC. Our aim was to determine the efficacy of Sym004 to circumvent cetuximab resistance driven by EGFR ECD mutations.Functional studies were performed to assess drug-receptor binding as well as ligand-dependent activation of individual EGFR mutants in the presence of cetuximab, panitumumab, and Sym004. Cell viability and molecular effects of the drugs were assayed in cetuximab-resistant cell lines and in tumor xenograft models. Efficacy of Sym004 was evaluated in patients progressing to cetuximab that harbored EGFR mutation in the post-cetuximab tumor sample.Contrary to cetuximab and panitumumab, Sym004 effectively bound and abrogated ligand-induced phosphorylation of all individual EGFR mutants. Cells resistant to cetuximab harboring mutations in EGFR maintained sensitivity to Sym004, which was consistent with an effective suppression of EGFR downstream signaling, translating into profound and sustained tumor regression in the xenograft model. As proof-of-principle, a patient with a tumor harboring an EGFR mutation (G465R) following cetuximab therapy benefited from Sym004 therapy.Sym004 is an active drug in MCRC resistant to cetuximab/panitumumab mediated by EGFR mutations. EGFR mutations are potential biomarkers of response to Sym004 to be evaluated in ongoing large clinical trials. Clin Cancer Res; 22(13); 3260-7. ©2016 AACR.
Potential of COX-2 inhibitors in lowering chemotherapy-induced neutropenia: Results from a randomized trial
Authors: L. W. Chow, A. Y. Yip, C. Lam, M. Toi
Journal: Journal of Clinical Oncology (2007)

19509 Background: This study was to evaluate the effect of celecoxib on the regimen 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) combination, followed by docetaxel in neoadjuvant setting. Patients and Methods: Twenty-three female patients with operable breast cancer were randomized into two groups: group A (n=12), four cycles of FEC (500 mg/m 2 , 100 mg/m 2 , 500 mg/m 2 ) followed by four cycles of docetaxel (100 mg/m 2 ) with concurrent celecoxib (400 mg twice daily); group B (n=11), same chemotherapy regimen but without concurrent celecoxib. These combined chemotherapies were administered 3-weekly. Results: 22 (96%) patients completed all cycles except that one (4%) omitted the fourth cycle of FEC owing to repeated incidences of febrile neutropenia. Received dose intensity (RDI) of group A and B for FEC (90% vs. 80%, p=0.035) and docetaxel (93% vs. 96%, p=0.414) showed significant difference in first four cycles of FEC between groups. Limiting hematological toxicity, severe neutropenia including febrile neutropenia, was significantly different between group A and B (33.3% vs 90.9%, p=0.005) during the first four cycles of FEC. Other toxicities commonly observed in chemotherapy receiving patients were manageable. Conclusion: Neoadjuvant use of FEC followed by docetaxel with concurrent celecoxib is safe for treatment of operable invasive breast cancer. COX-2 inhibitor likely lowers the incidence of chemotherapy-induced neutropenia. We believe that further investigation might provide more evidence on the use of COX-2 inhibitors in breast cancer. No significant financial relationships to disclose.
Incidence of non-metastatic extrathoracic lesions detected by whole-body FDG PET-CT imaging in patients with non-small-cell lung cancer
Authors: D. Lardinois, H. C. Steinert, M. Tutic, G. Görres, R. Stahel, W. Weder
Journal: Journal of Clinical Oncology (2004)

7186 Background: To assess the incidence and nature of unsuspected extrathoracic focal increased FDG accumulation in patients with non-small-cell lung cancer (NSCLC) staged with whole-body integrated PET-CT. Methods: Whole-body integrated PET-CT scans for staging of NSCLC were analysed in a consecutive series of 300 patients, including 212 men and 88 women, with a mean age of 67 years (range 36–84 years). After application of 350–400 MBq FDG, whole-body PET-CT was performed (Discovery LS, GE Medical System). Every solitary unsuspected focal abnormality was interpreted as highly suspicious for a metastasis. The true diagnosis was confirmed histopathologically. Results: PET/CT imaging revealed 99 unsuspected extrathoracic lesions. Beside 62 lung cancer metastases, tumor unrelated focal abnormalities were found in 37 (12.3%) patients, which represents 37.4% of all the extrathoracic findings. Histopathologic correlation could be obtained in 89.2% of these 37 patients and revealed 6 malignancies including carcinoma of the breast in 2 patients, carcinoma of the orbit, oesophagus, prostate, non-Hodgkin lymphoma in one patient each, as well as 27 benign tumors or inflammatory lesions. These 27 lesions consisted of 3 Warthin's tumors, 1 granuloma of the lower jaw, 1 adenoma of the thyroid gland, 1 compensatory muscle activity due to vocal chord palsy, 2 arthritis, 4 reflux oesophagitis, 2 pancreatitis, 4 diverticulitis, 7 adenomas of the colon, 1 haemorrhoid, and 1 extra-uterine pregnancy. Conclusions: The critical analysis of additional PET positive lesions which may mimic metastases of NSCLC is important for correct staging and optimal therapy. No significant financial relationships to disclose.
Human Immunodeficiency Virus Type 1 Nef Protein Sensitizes CD4+ T Lymphoid Cells to Apoptosis via Functional Upregulation of the CD95/CD95 Ligand Pathway
Authors: Giorgio Zauli, Davide Gibellini, Paola Secchiero, Hélène Dutartre, Daniel Olive, Silvano Capitani, Yves Collette
Journal: Blood (1999)
Down-regulation of MDR1 by epigenetic alteration in human epithelial ovarian cancer cells
Authors: Y. Kawakami, K. Miyamoto, K. Takehara, M. Kumagai, O. Samura, H. Nakamura, T. Mizunoe, H. Yoshida, K. Taniyama, F. Saji
Journal: Journal of Clinical Oncology (2009)

e16556 Background: Ovarian cancer is one of the most lethal malignancies in women. Despite recent studies of many oncogenes and tumor-suppressor genes concerning about its progression, the details of ovarian cancer biology still remains to be unclear. P-glycoprotein (P-gp) encoded by the MDR1 gene is a membrane protein that can export many kinds of antineoplastic agents from cells, and overexpression of P-gp has been reported to be implicated in treatment failure in cancer. DNA methylation, a major epigenetic process, can affect every step in carcinogenesis as well as genetic alterations. The contribution of such epigenetic alteration to the expression of MDR1 remains largely unexplored in human ovarian cancer. Methods: In this study, we evaluated the DNA methylation status of the MDR1 gene by methylation-specific PCR. Then, the expression of MDR-1 mRNA and protein in primary epithelial ovarian cancer specimens were evaluated by real-time RT-PCR and immunohistochemistry using anti-mouse P-gp F4 monoclonal antibody, respectively. The correlation between these results and clinicopathological features was examined. Results: MDR1 was hypermethylated in 12 of 12 (100%) ovarian cancer cell lines, and 5 of 13 (38%) primary ovarian cancers by methylation-specific PCR analysis. MDR1 mRNA expression was subsequently found to be lost in ovarian cancer cell lines with methylation by both real-time RT-PCR and immunohistochemistry. Thus, MDR1expression was associated with the DNA methylation status of the MDR1 gene. Conclusions: In conclusion, MDR1 was frequently hypermethylated in human ovarian cancers. Our results suggest that epigenetic regulation might play a role in the expression of MDR1 and clinical treatment outcomes in human ovarian cancer. No significant financial relationships to disclose.
Prospective Evaluation of Cardiac CT in Reoperative Cardiac Surgery
Authors: Andrew D. Choi, Vijaywant Brar, Kalyan Kancherla, Omid Fatemi, Geetha Pinto, Steven Boyce, Ammar Bafi, Paul J. Corso, Eshetu Tefera, Allen J. Taylor, Wm. Guy Weigold, Gaby Weissman
Journal: JACC. Cardiovascular imaging (2016)
Population Screening for Breast Cancer by Single-View Mammography in a Geographic Region in Sweden
Authors: Bengt Lundgren, M.D.
Journal: JNCI Journal of the National Cancer Institute (1979)

Single-view mammography was used for the screening of a total population of women living in a defined geographic region in Sweden; 37,640 women were invited and 31,074 participated. The average participation rate was 82.6%, and in the age group 40–69 years it was 91.7%. The rate of referrals from screening to clinical examination was 1.2%. Of 209 surgical biopsies performed, 130 primary mammary carcinomas were detected, 91% of which had no clinically detectable meta-static nodes. Because of the few false-positive cases, the low rate of benign biopsy specimens, the high rate of early detected carcinomas, and the low costs, screening by single-view mammography is considered a satisfactory method, provided the positioning of the oblique view is correct and the image quality is high.
What troubles women starting chemotherapy (CT) for advanced breast cancer (ABC) in a randomized trial?
Authors: A. K. Nowak, K. Byth, V. Gebski, A. K. Fong, A. S. Coates, V. Harvey, M. Stockler
Journal: Journal of Clinical Oncology (2004)

8144 Background: Many women with ABC are unsuited to intensive CT, but little is known about their concerns and attitudes to treatment. ANZ0001 will determine if oral capecitabine is preferable to CMF as first line CT in women with ABC unsuited to more intensive CT. This report describes baseline characteristics, quality of life (QL) and attitudes in the first 150 women randomized. Methods: Before starting CT, women completed 4 validated QL tools (GLQ-8, LASAS, Uniscale, UBQ-C) and study specific scales assessing symptoms, functions, global ratings and treatment concerns. Scores are reported on a scale from 0 to 10: for symptoms and concerns, 0 is best and 10 worst; for functions and global ratings, 0 is worst and 10 best. Results: 148 of 150 (99%) women completed at least 1 form and 90–99% of items were completed. Baseline characteristics were median age: 62 (IQR 54–69); ECOG PS 0–1: 86%, 2–3: 14%; liver or brain metastases: 47%; prior adjuvant CT: 37%. Mean scores for health state (6.7) and overall QL (6.6) were high with 55% rating their general health as good, very good or excellent. The 5 aspects rated worst before starting CT (mean) were: uncertainty about the future (4.2), the thought of CT (3.9), lack of energy (3.7), pain (3.6), feeling anxious/worried (3.0); whereas problems with needles or injections (1.5), inconvenience of treatment (0.7), problems coping with treatment (0.6), and problems taking tablets (0.3) were rated lower. More women were severely distressed (rated 7 or more) about thought of CT (23%) and uncertainty about the future (25%), than about problems with injections or needles (10%) or taking tablets (1%). Distress about the thought of CT was most correlated with uncertainty about the future (r = .58, p<.0001) and other emotional aspects (r = .23 to .45, p<.006), whereas problems with needles, injections and tablets were more correlated with physical aspects (r = .18 to .31, p<.04). Conclusions: Before starting CT, these women rated their general health and overall QL highly despite moderate symptoms. They were most distressed by the thought of having CT and uncertainty about the future, and least distressed about needles, injections and taking tablets. No significant financial relationships to disclose.
An Australian experience of pemetrexed in malignant mesothelioma (MM)
Authors: A. M. Joshua, M. E. Burge, C. M. McNeil, R. Hui, M. J. Boyer, R. Abraham
Journal: Journal of Clinical Oncology (2004)

7285 Background: Pemetrexed and cisplatin have recently been shown to significantly improve survival compared to cisplatin alone. However there is only limited data available in a teaching hospital setting outside a clinical trial. Pemetrexed has only been available in Australia on a “special access scheme”(SAS) since 2002. We reviewed our experience of patients treated on the SAS at three major thoracic oncology units. Methods: Charts were reviewed for all patients enrolled on the scheme. Data was extracted on age, ECOG performance status, histology, prior therapy, time from diagnosis to starting pemetrexed, chemotherapy (pemetrexed alone or with a platinum), cycle number, response rate, actuarial progression free and overall survival. All patients received vitamin B12 and folate supplementation. Doses were cisplatin 75 mg/m2 or carboplatin AUC=5 and pemetrexed 500mg/m2 every 21 days. Results: 52 patients (32 male and 20 female) were reviewed. Median age was 58 years. 88% were ECOG 0–1. Histology included 54% epithelial, 17% biphasic (epithelial and sarcomatoid) and 21% undefined. The median time from diagnosis to administration of pemetrexed was 145 days. 65% had minimal surgical intervention with video assisted thoracoscopy, pleurodesis and biopsy whilst 19% had received prior palliative radiation. 71% were chemotherapy naïve, the remaining 29% having received previous platinum and/or gemcitabine regimens. 23% had pemetrexed alone, 35% in combination with carboplatin and 42% with cisplatin. Median number of cycles was 4 (range 1–13). Response rate was 25%. No toxicity was observed in 20%, grade 3–4 toxicity in 10% (majority nausea/vomiting). Median progression free and overall survival times from starting pemetrexed were 184 days and 298 days respectively. Conclusions: Pemetrexed is safe and effective in a community setting in MM with results comparable to the recent phase III trial. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly Eli Lilly
Capecitabine (X) combined with radiotherapy in Chinese patients (pts) with advanced or relapsed rectal carcinoma
Authors: W. Shen, Y. Liu, X. Ma, J. Che, Z. Zeng, Y. Li, G. Li, R. Wang, W. Zhang, X. Liu
Journal: Journal of Clinical Oncology (2004)

3671 Background: Colorectal cancer is one of the most common malignancies in China. X (Xeloda) is an oral fluoropyrimidine that is preferentially converted to 5-FU by exploiting the higher concentrations of thymidine phosphorylase (TP) in tumors compared to normal tissue. When combined with radiotherapy (which also upregulates TP), X is highly active and well tolerated for the preoperative treatment of locally advanced rectal cancer. Because few Chinese data are available, we evaluated X chemoradiation in Chinese pts with advanced/relapsed disease. Methods: We enrolled 100 pts between Jun 2002 and Oct 2003. All had measurable advanced or relapsed rectal carcinoma, and adequate Karnofsky PS, bone marrow, renal and hepatic functions. Adjuvant fluoropyrimidines (≥1 months previously) and/or prior radiotherapy to sites other than those evaluated in the trial were permitted. Pts received a total radiation dose of 60 Gy (1.8 Gy/day) for approximately 6 weeks plus X 825 mg/m2 twice daily for the duration of radiotherapy. Results: Baseline characteristics of the 71 pts currently evaluable: 51 men, 20 women; median age 51 years (range 18–75); median Karnofsky PS 90 (range 60–100); 86% pts had one disease site, 14% had ≥2, the most common being the rectum (51%), pelvis (44%), and skin (7%). 92% pts received the full 6 weeks' treatment, 6% stopped at week 5, 1% each at weeks 3 and 4. To date, at treatment end 46/71 pts have responded (65%) with only 4 progressions. At 4 weeks post-chemoradiation, responses have been confirmed in 34/59 pts (59%), of which 8 are complete (15%). Median progression-free and overall survival have not yet been reached. There were no grade 4 and very few grade 3 adverse events (HFS, 3%; diarrhea, 3%; nausea, 1%), which were easily managed with dose adjustment and supportive treatment when required. Conclusions: X chemoradiation is active and very well tolerated in Chinese pts with advanced or relapsed rectal carcinoma, reflecting the results obtained in Europe and the US. Use of this convenient regimen in the neoadjuvant and recurrent settings is clearly warranted. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca Pharmaceuticals
An international pooled analysis identifying predictive factors associated with toxicities in phase I trials (Delphi).
Authors: C. A. Gomez-Roca, C. Baey, D. Olmos, A. Berens, E. Bigger, P. LoRusso, M. L. Rothenberg, S. B. Kaye, J. Pignon, J. Soria
Journal: Journal of Clinical Oncology (2010)

2517 Background: Phase I trials aim at identifying suitable dose levels and toxicity profiles of novel drugs or combinations for further evaluation in phase II trials. In most of these trials, the appearance of serious toxic events determines the maximum tolerated dose. Eligibility criteria are traditionally used in order to select those patients who could potentially benefit from trial participation with a minimal risk of developing toxicity. Nevertheless, better tools for identifying patients at high risk of toxicity are warranted. Methods: Patients treated in phase I trials from four major American and European Cancer Centers were included from December 2002 to December 2007. Grade 3 and 4 (G3-4) toxic events were recorded as well as clinical and biological characteristics at baseline. The prognostic value on toxicities of these factors was assessed using logistic models, stratified on center. Results: A total of 810 patients were included in 146 phase I trials. Of those patients, 357 presented at least one G3-4 toxic event. Median age was 58 years, with 56% male. Forty-nine percent of patients received a targeted therapy (TT) as single agent, while 42% and 9% received a combination of a cytotoxic drug + TT or a combination of TT, respectively. A multivariate analysis of 11 out of 19 clinical and biological factors selected after univariate analysis showed a higher risk of G3-4 toxicity in patients with lymphocytes count inferior to 700/mm3 (OR 1.84 [1.17-2.90]) and platelets count inferior to 400,000/mm3 (OR 1.66 [1.09-2.52]). Patients included in phase I trials combining cytotoxic drug and a TT or TT among them showed a higher risk of serious toxic events (OR 2.32 [1.67-3.247] and OR 3.57 [1.90-6.472], respectively). Conclusions: Our data showed that patients' clinical and biological values present at the time of inclusion could predict a higher risk of serious toxic events in phase I trials. Trials exploring combination treatments are at highest risk. The data of an additional 400 patients is expected at the time of the Meeting. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer Roche
Abstract 090: Long-term Therapy with a Bendavia (MTP-131), a Novel Mitochondria-Targeting Peptide, Normalizes Cardiolipin Biosynthesis and Remodeling in Left Ventricular Myocardium of Dogs with Advanced Heart Failure
Authors: Hani N Sabbah, Quan He, Ramesh C Gupta, Sharad Rastogi, Mengjun Wang, Keife Zhang
Journal: Circulation Research (2013)
Diagnosis of recurrent breast cancer: 18F-FDG PET/TAC as first choice
Authors: M. Mion, F. Chierichetti, G. Liessi, S. Bissoli, E. Milan, F. Oniga, L. Sartor, M. Bortolin, G. Vicario, G. Sgarbossa, P. Manente
Journal: Journal of Clinical Oncology (2006)

10681 Background: we began using PET diagnosis in 1994 and since the beginning of 2000 we started with a PET/CT system. Aim of our study was to evaluate if this new imaging modality may be the first step in the detection of recurrence in patients with a history of breast tumors. Methods: we reviewed retrospectively 22 patients (mean age 60, range 46–76 years) already treated for a breast cancer. A total of 32 PET/CT scans were performed (repeated in 10 patients). All patients were submitted to other examinations, such as bone scintigraphy and liver ecography, but also mammography and CT scan. Results: 14/32 PET/CT were negative for recurrence in 10 patients (4 scans as a second one). In a mean follow up of 10 months, 1 case is not yet clear: in presence of relevant increase of Ca15.3 (up to 176 ng/ml) the first scan was negative and the second one evidentiated a pattern of lung inflammation. Among the other 13/14 negative scans, 3 patients presented ambiguous/positive bone scintigraphy for metastases, not assessed at the final diagnosis. 18/32 PET/CT scans were positive for local recurrence or distant metastases. Among these positive cases, a patient with normal bone scintigraphy presented a mild uptake of FDG in the right omerus. The second scan (5 months later) showed focal increased uptake of FDG in the same bone site, not evident in the CT images, and many small lung nodules, 1–2 mm size. In 3 patients PET localized muliple bone lesions, in 2 CT was completely normal. Finally, 1 out of the 18 positive results was false positive: a patients with a single lung nodule (1.5 cm) was submitted to surgery and the final diagnosis was benign lesion. PET/CT was crucial for the patient’s management in 19 out of 22 patients. Conclusions: recurrent breast cancer is generally characterized by multiple sites of metastases and few cases take advantage of surgical resection. In our group of 22 patients just 2 out of them received surgery (for local relapse and lung metastases). Therefore, in most cases a whole body examination, like PET/CT may be more useful respect to other modalities to assess how spread is the recurrence. Further data are needed but, in our preliminary experience, PET/CT seems to be the first choice to evaluate patients with previous breast cancer. No significant financial relationships to disclose.
William Moncrieff Haining
Authors: Nick Haining, Carrie MacEwan
Journal: BMJ (2016)

William Moncrieff Haining, who has died aged 88, was an ophthalmologist, clinical innovator, and mentor, who founded the eye unit at Ninewells Hospital in Dundee and led it for almost 30 years.

Born in Durban, South Africa, where his father, a Scottish engineer with the Cable and Wireless Company, had been posted, he spent his childhood in Lockerbie, near Dumfries. He trained in medicine at the University of Edinburgh, where he was influenced by the great anatomists of the day, and in particular by the striking imagery captured in the anatomical plates painted by Edward Bald Jamieson. “Wee Jimmies,” as they were known, demonstrated to him the power of visualising anatomy in understanding pathology, something that later was to inspire his research in retinal angiography.

He completed his house jobs in Carlisle, Edinburgh, and Bangour, where he met Barbro, a blonde, blue eyed Norwegian physiotherapist, who was to become his wife of 57 …