tbuckley/cabot-search huggingface dataset:
Gene signatures as predictors of response to neoadjuvant chemotherapy (NCT) with docetaxel, doxorubicin, cyclophosphamide (TAC), or AC and nab-paclitaxel (nab-P) and carboplatin ± trastuzumab in patients (pts) with stage II-III and inflammatory breast cancer (IBC).
Authors: G. Somlo, P. H. Frankel, L. Vora, S. Lau, T. H. Luu, L. Kruper, J. Yim, Y. Yen, F. de Snoo, R. A. Bender
Journal: Journal of Clinical Oncology (2010)

540 Background: Pathologic complete response (pCR) and residual cancer burden (RCB) scores of 0 (pCR) and 1 (near CR) after NCT predict for better survival (Symmans et al. J Clin Oncol 25:4414-22, 2007). Improved NCTs and molecular markers predicting for response are needed. Methods: Pts with HER2- BC were randomized to receive 6 cycles of docetaxel 75 mg/m2, doxorubicin 50 mg/m2, cyclophosphamide 500 mg/m2 (TAC, Arm A) versus A 60 mg/m2 and C 600 mg/m2 given every 2 weeks × 4, followed by 3 weekly doses of carboplatin (carbo) at an AUC 2,and nab- P 100 mg/m2, repeated as 28 day cycles × 3 ( Arm B). Pts with HER2+ BC (by immunohistochemistry [IHC] and/or FISH) received NCT as per Arm B, but, with trastuzumab (trast) given weekly with carbo and nab (Arm C). Core biopsies were taken pre-NCT. 70-gene (MammaPrint) profiling for poor vs. good risk features, and 80-gene profiling for basal, HER2+, and luminal subtypes were performed. We assessed the predictive value of gene profiling for response to NCT, as a function of RCB scores of 0-1 vs. > 1. Results: Pre-NCT fresh tissue was procured from 97 pts. Pts were treated for stage II (49%), III (locally advanced [51%] and IBC [16%]) BC; 57% of BCs were ER and/or PR+ and 36% were HER2+ (by IHC/or FISH). RCB scores were available in 90% of pts enrolled (10% is awaiting surgery): scores of 0-1 were observed in 29% pts treated on either Arms A or B, and in 64% of pts treated on Arm C. There was 98% concordance of HER2- BCs by IHC/FISH vs. gene profiling; 35% of HER2+ BCs by IHC/FISH were HER2- by gene profiling. Of the 25 pts with response data on Arm C, 8 of 19 pts who were HER2+ by both IHC/FISH and HER2+ gene profiling, achieved pCR (RCB 0), vs. 2 of 6 pts with HER2+ BC by IHC/FISH, but with HER2- gene profiles (p-value: 0.04). A poor-prognosis signature by the 70-gene assay was observed in 76% of BCs. Conclusions: BC with HER2+ gene profile is the most likely to respond with pCR (RCB 0) to trastuzumab-containing NCT. RCB scores as a function of NCT, molecular subtypes, and poor vs. good risk profile in the entire pt population will be presented. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Agendia Abraxis BioScience Agendia Abraxis BioScience
Ewing sarcoma family tumors (ESFT) as second malignant neoplasms (SMN) following treatment of a primary malignant neoplasm (PMN) during childhood
Authors: S. L. Spunt, J. A. Harper, M. J. Krasin, C. A. Billups, C. Rodriguez-Galindo
Journal: Journal of Clinical Oncology (2004)

8539 Background: ESFT comprise approximately 2% of malignancies in childhood. Although there are scattered reports in the literature of ESFT as a SMN, the proportion of SMN that are ESFT is unknown. Methods: We reviewed our institutional experience from 3/62 to 12/03 with ESFT arising as a SMN. Demographic data, diagnostic and treatment information for both the PMN and SMN, and outcome data were recorded. Results: Of the 431 patients with 2 or more malignancies, 8 (1.9%) had ESFT as a SMN. The median age at diagnosis of PMN was 4.2 years (range, 0.8–12.5 years), and of ESFT was 13.4 years (range, 4.9–22.0 years). Five patients were female and 7 were white. The PMN was retinoblastoma (n=3), Wilms tumor (n=2), acute lymphoblastic leukemia, Hodgkin lymphoma, and non-Hodgkin lymphoma (n=1 each). Six patients received chemotherapy for treatment of the PMN including alkylating agents (n=3), anthracyclines (n=6), and etoposide (n=1). Four also received radiotherapy (RT) for the PMN (dose range, 10.8–48 Gy, median 30 Gy). The median latency between the PMN and ESFT was 6.3 years (range, 3.1–18.3 years). The ESFT primary sites were chest wall/rib (n=4), extremity (n=3) and pelvis (n=1). Three patients had metastases at presentation. Among the 4 patients who had received RT previously, 2 ESFT arose outside the field and 2 arose at the field margins. Four patients have died: 3 due to progressive ESFT and 1 due to a third malignancy (osteosarcoma arising within the RT field used to treat the ESFT). The 5-year estimated survival following the development of ESFT was 57.1%±16.7%. Conclusions: The proportion of ESFT as a SMN following treatment of childhood cancer is similar to the proportion of ESFT as a PMN in childhood. Patients with retinoblastoma may be at higher risk than other childhood cancer survivors for secondary ESFT. Most secondary ESFT are not radiation-induced. Survival appears to be only slightly inferior to that of de novo ESFT. No significant financial relationships to disclose.
The interleukin-6 receptor alpha-chain (CD126) is expressed by neoplastic but not normal plasma cells
Authors: Andy C. Rawstron, James A. L. Fenton, John Ashcroft, Anne English, Richard A. Jones, Stephen J. Richards, Guy Pratt, Roger Owen, Faith E. Davies, J. Anthony Child, Andrew S. Jack, Gareth Morgan
Journal: Blood (2000)
Abstract 11800: The Influence of Post Percutaneous Coronary Intervention Activated Clotting Time Level on In-hospital and Short-term Clinical Outcomes in the Drug-eluting Stent Era
Authors: Sung Il Im, Seung Woon Rha, Byoung Geol Choi, Se Yeon Choi, Amro Elnagar, Sun Won Kim, Jin Oh Na, Seong Woo Han, Cheol Ung Choi, Hong Euy Lim, Jin Won Kim, Eung Ju Kim kim, Chang Gyu park, Hong Seog Seo, Dong Joo Oh
Journal: Circulation (2012)

Background: There are very limited data investigating the influence of post percutaneous coronary intervention (PCI) activated clotting time (ACT) level on the in-hospital and short-term clinical o...
Abstract 19342: High-Sensitivity C-Reactive Protein Effects of Icosapent Ethyl (Eicosapentaenoic Acid Ethyl Ester) With and Without Stable Statin Therapy in Hypertriglyceridemic Patients With Metabolic Syndrome
Authors: Harold Bays, Christie M Ballantyne, Rene A Braeckman, William G Stirtan, Paresh N Soni
Journal: Circulation (2013)

Introduction: Elevated high-sensitivity C-reactive protein (hsCRP) is a marker for increased cardiovascular disease (CVD) risk. The metabolic syndrome (MetSyn) is a collection of CVD risk factors and includes high triglyceride (TG) levels as a diagnostic criterion. Statins reduce hsCRP. The combination of eicosapentaenoic acid (EPA) and/or docosahexaenoic acid (DHA) has not been shown to consistently lower hsCRP levels. Icosapent ethyl (IPE; formerly AMR101) is a high-purity prescription form of EPA ethyl ester approved to reduce TG levels in patients with severe (&gt;=500 mg/dL) hypertriglyceridemia. Hypothesis: We evaluated the relative hsCRP effects of IPE in patients with and without statin therapy among hypertriglyceridemic patients with MetSyn. Methods: The MARINE study was a multicenter, placebo-controlled, double-blind, 12-week study of 229 randomized patients with TG &gt;=500 and &lt;=2000 mg/dL. This analysis evaluated the effect of IPE on hsCRP in a subset of patients from the MARINE study with MetSyn. Results: The MARINE study included 204 patients from the intent-to-treat population with MetSyn. Compared to placebo, IPE 4 g/day significantly reduced blood levels of TG (35%; p&lt;0.0001), non-high-density lipoprotein cholesterol (19.9%, p&lt;0.0001), apo B (9.1%, p=0.0015), and hsCRP (40%, p=0.0007), without a significant increase in low-density lipoprotein cholesterol. IPE 4 g/day also reduced hsCRP levels by 27.6% (p=0.0385) and 78.0% (p=0.0035) compared to placebo in non-statin-treated (n=48) and statin-treated patients (n=16), respectively. Conclusion: Compared to placebo, when administered to hypertriglyceridemic patients with MetSyn, IPE 4 g/day improved lipid levels and reduced hsCRP. Compared to placebo, IPE reduced hsCRP more in stable statin-treated patients than in those not treated with statins.
Oligodendroglioma: a new chemosensitive tumor.
Authors: J G Cairncross, D R Macdonald
Journal: Journal of Clinical Oncology (1990)

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.1990.8.12.2090 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 2230902 Oligodendroglioma: a new chemosensitive tumor. J G CairncrossxJ G CairncrossSearch for articles by this author , D R MacdonaldxD R MacdonaldSearch for articles by this author https://doi.org/10.1200/JCO.1990.8.12.2090 PDF "Oligodendroglioma: a new chemosensitive tumor.." Journal of Clinical Oncology, 8(12), pp. 2090–2091© 1990 by American Society of Clinical Oncology
Impact of the clip and snare method using the prelooping technique for colorectal endoscopic submucosal dissection
Authors: Shinya Yamada, Hisashi Doyama, Ryosuke Ota, Yasuhito Takeda, Kunihiro Tsuji, Shigetsugu Tsuji, Naohiro Yoshida
Journal: Endoscopy (2015)

Endoscopic submucosal dissection (ESD) is more difficult to perform for colorectal tumors, but the use of traction to facilitate direct submucosal layer visualization is a promising method to reduce procedure times and complication rates. This study aimed to evaluate the efficacy and safety of the clip and snare method (CSM) with a prelooping technique (PLT) for colorectal tumors.A total of 140 colorectal tumors were treated: 17 using the CSM with PLT; 123, used as controls, by standard ESD without these techniques. Therapeutic efficacy and safety were retrospectively assessed.All tumors were successfully resected en bloc using the CSM with PLT. Multisegment resection was found in four tumors in the control group. There was a significant difference in the procedure time between the patients in the CSM with PLT group and the control group (45.6 vs. 70.1 minutes; P = 0.047). There were no significant differences in the complication rates (5.9 % vs. 8.1 %; P = 1.00).The CSM with PLT was effective and safe in this study.
Multimedia: American Surgery, An Illustrated History
Authors: William Stoney
Journal: BMJ (1999)

Ira M Rutkow


Lippincott Williams and Wilkins, £52.93, pp 656 




ISBN 0 316 76352 7

———————

Rating: ★★★★

When you think about it, much of surgical teaching is based on history, particularly teaching done in the operating room. Surgical residents learn early in their training that it is not necessary to repeat mistakes made in the past, and that every useful operation has evolved through a process of trial and error. The concept of standing on the shoulders of giants is not lost on the present generation of surgeons. When asked to discuss a surgical procedure, most surgeons will begin by describing the origins of the operation and the surgeon associated with its development. Surgeons like history.

They will like this book. It begins with surgical practice in the colonial era, moves on to the introduction of anaesthesia, the treatment of injuries in the civil war, antisepsis and asepsis, both world wars, the age of specialisation, and ends with a discourse on recent controversies such as Medicare, surgical staffing studies, managed care, and declining remuneration. Along the way, there are excellent biographical accounts of major participants of each era. Probably the best and most detailed of these is that of William Stewart Halstead, who is represented honestly but with sensitivity and understanding. Halstead’s ideas about surgical training and the development of what has become our surgical training system are well documented. Also of interest to me was the founding of the American College of Surgeons and its profound influence on hospital standards of care, credentialing, and records.

This chronological history fills the first 400 pages and is followed by a shorter section containing brief histories of surgical specialties, each including a short biographical description of 10 or 12 key pioneers and prominent surgeons. For reasons not explained, vascular surgery is not included. Also, the author has chosen not to include any living surgeons in this biographical material, so that several prominent cardiac and vascular surgeons such as Michael DeBakey, Denton Cooley, and C Walton Lillehei are only briefly mentioned.

Some of the strongest messages of this book come from the numerous illustrations, which in some way reveal more about the past than does the text. These lithographs, paintings, illustrations, and photographs are each described in detail and, even if presented alone, would be an adequate history. For example, the section on the civil war begins with a photograph of a stack of a dozen amputated legs, poignantly symbolic of that tragic episode. The illustrations are the most moving part of the book.

This is an outstanding book and will be the standard by which future historical collections of American surgery will be measured.
Clinical relevance of mesenchymal stem cell–induced resistance to chemotherapy.
Authors: J. M. L. Roodhart, L. G. Daenen, E. C. Stigter, R. H. Medema, A. C. Martens, A. B. Brenkman, E. E. Voest
Journal: Journal of Clinical Oncology (2011)

10557 Background: The role of mesenchymal stem cells (MSCs) in tumor growth and metastasis is well established. We recently showed in mouse models that MSCs induce resistance to a broad spectrum of chemotherapies via a paracrine mechanism. Via a metabolomics approach we identified two unique platinum-induced polyunsaturated fatty acids (PIFAs): KHT(n-6) and 16:4(n-3) responsible for the induction of resistance by MSCs. Here we determined whether these findings could be translated to the human situation. Methods: Blood samples from cancer patients were analyzed for MSC levels by FACS analysis and PIFA levels by mass spectrometry. A xenograft model for human breast cancer was established. Recruitment of MSCs to tumors was mimicked by iv administration of human MSCs isolated from the bone marrow of healthy volunteers. Results: MSC levels were significantly increased in peripheral blood of cancer patients with metastatic disease compared to cancer patients after radical resection of the tumor (p <0.05), indicating that MSCs are recruited to the circulation in the presence of a tumor and will be exposed to chemotherapy. Human MSCs were injected iv in nude mice with subcutaneous MDA-MB-231 tumors. Each human MSC-isolate induced a similar chemotherapy resistance as previously observed by mouse MSCs, resulting in tumor growth similar to the untreated controls. We confirmed the secretion of 16:4(n-3) and KHT(n-6) by platinum-activated human MSCs similar to the mouse MSCs. Finally, we measured the levels of 16:4 (n-3) in plasma samples from 10 esophageal cancer patients treated with cisplatin-based chemotherapy and 10 breast cancer patients treated with non-platinum based chemotherapy. In an exploratory analysis we found a significant increase in 16:4 (n-3) hours after treatment with cisplatin-based chemotherapy compared to patients treated with non-platinum based chemotherapy (p 0.04). Conclusions: Based on preclinical and exploratory clinical data, we conclude that the novel mechanism of resistance via the release of PIFAs by MSCs can be translated to patients. Evidence from human material shows a conserved function of MSCs, which points to the clinical importance of platinum-based activation of MSCs in relation to therapy response.
Frequency of β-catenin heterozygous mutations in extra-abdominal fibromatosis as a surrogate marker for disease management
Authors: J. Dômont, S. Salas, L. Lacroix, V. Brouste, A. Dufresne, P. Terrier, J. Blay, A. Le Cesne, J. Coindre, J. Benard, S. Bonvalot
Journal: Journal of Clinical Oncology (2009)

10501 Background: Fibromatosis, a rare soft-tissue and locally invasive neoplasm, consist of distinct clinical entities including sporadic extra-abdominal fibromatosis (EAF). The potential morbidity of loco-regional treatments combined with the high local recurrence rate have led investigators to assess the possibility to design a “wait and see” policy in a subset of patients (pts). Up to date, molecular biomarkers of local recurrence of EAF remain unknown. As dysregulation of β-catenin (βC) expression hallmarks fibromatosis, herein we searched for βC mutations in a large retrospective European multi-centric tumors series to relate with clinicopathologic parameters. Methods: From 1987 to 2007, 155 pts with fibromatosis from all sites were gathered by the Conticanet Network were analysed. Direct sequencing of exon 3 βC gene was performed for 155 frozen tissues. All mutated cases were confirmed by an independent analysis. From this cohort, 101 pts with EAF surgically treated with curative intent and follow-up allowed us to relate βC mutational status to disease outcome. Results: Mutations of βC were detected in 84% of all cases. Among 101 pts with EAF surgically treated, similar mutations types and rates (87%) were observed, namely T41A (39.5%), S45P (9%), S45F (36.5%) and deletion (2%). There were 36 men and 65 women. Majority of pts were treated for primary EAF (57%). Most of surgical margin were RO (38%) or R1 (34%). Few pts were treated after surgery with radiation therapy (18%) and medical treatment (8%). With a median follow-up of 62 months, 51 pts (51%) relapsed. Neither clinicopathologic parameters were found to be significantly associated with βC mutational status. The five-year recurrence free-survival was significantly worse in βC mutated tumors regardless of a specific genotype, than in wild-type tumors (49 versus 93%, respectively, p=0.02). No significant difference was observed in considering either T41A, or S45F or S45P mutants, even if 45Fmutation appears to show a weak trend of significance for a dismal outcome. Conclusions: A high frequency (87%) of βC mutation hallmarks EAF from a large multicentric retrospective study. Moreover, wild type βC appears as a good prognosis marker that can be useful for therapeutic management of the EAF. [Table: see text]
FGF21 Lowers Plasma Triglycerides by Accelerating Lipoprotein Catabolism in White and Brown Adipose Tissues
Authors: Christian Schlein, Saswata Talukdar, Markus Heine, Alexander W. Fischer, Lucia M. Krott, Stefan K. Nilsson, Martin B. Brenner, Joerg Heeren, Ludger Scheja
Journal: Cell Metabolism (2016)
Elevated plasma TIMP-1 levels predict reduced survival in metastatic hormone-refractory prostate cancer patients
Authors: W. K. Oh, K. Leitzel, P. W. Kantoff, M. M. Regan, P. Hamer, K. Pierce, S. Brown-Shimer, W. Carney, S. M. Ali, A. Lipton
Journal: Journal of Clinical Oncology (2007)

5143 Background: Tissue inhibitor of metalloproteinase-1 (TIMP-1) has been shown to have parodoxical multifunctional roles in tumorigenesis: inhibition of the catalytic activity of MMPs, growth promotion, inhibition of apoptosis, and regulation of angiogenesis. Increased TIMP-1 has been associated with an unfavorable prognosis in many cancers including breast, colorectal, gastric, head and neck, lung cancer, and lymphomas. Methods: EDTA plasma TIMP-1 was determined from 60 hormone-refractory prostate cancer (HRCaP) patients using the TIMP-1 ELISA from Oncogene Science / Bayer HealthCare, Cambridge, MA. Patients were identified from an institutional database and had metastatic, HRCaP at the time of blood collection, which ranged from &lt;1 month to 14 yrs. after the start of androgen-deprivation therapy (ADT); some patients had also received several chemotherapy regimens by the time of blood collection. Median follow-up was 17 mo. after blood collection and 27/60 patients had died. Overall survival was analyzed using Kaplan-Meier method and Cox modeling on tertiles of the TIMP-1 distribution. Results: The median EDTA plasma TIMP-1 level from the 60 HRCaP patients was 335 ng/ml (range 21 - 1391 ng/ml). Median survival since time of blood collection was 14 mo. Survival differed across TIMP-1 levels (P&lt;0.01, logrank test), in particular the upper tertile of plasma TIMP-1 had a significantly reduced overall survival from the time of blood collection compared to the lowest tertile: A larger confirmatory study which will include a multivariate analysis of known prognostic factors is planned. Conclusions: Elevated plasma TIMP-1 tertile level predicted reduced survival in HRCaP patients. Soluble TIMP-1 deserves further study to determine its predictive and prognostic biomarker potential in a larger cohort of prostate cancer patients. [Table: see text] [Table: see text]
Unusual Response to Androgen of Estrogen-Dependent Mammary Tumors
Authors: J. Harry Cutts
Journal: JNCI Journal of the National Cancer Institute (1969)

Estrogen-dependent mammary tumors acquire a resistance to treatment with testosterone. Infrequently and randomly some tumors develop an ability to utilize testosterone as well as estrogen, and with androgen such tumors fail to regress when the estrogen source is removed. These tumors regress only when treatment with testosterone is discontinued, but the male hormone is not necessary for reinduction of tumor.
A phase II evaluation of mitolactol in patients with advanced squamous cell carcinoma of the cervix: a Gynecologic Oncology Group Study.
Authors: F B Stehman, J A Blessing, R McGehee, R J Barrett
Journal: Journal of Clinical Oncology (1989)

Sixty patients with advanced squamous cell carcinoma of the cervix (SCC) who had received no prior chemotherapy were entered onto a study of mitolactol (dibromodulcitol [DBD]). The drug was administered orally at an initial dose of 180 mg/m2 per day for 10 days and repeated every 4 weeks. There were 55 evaluable patients, of whom one (2%) had a complete response (CR), and 15 (27%) had a partial response (PR), (CR plus PR, 29%). A 95% confidence interval for the true response rate is 18.8% to 42.1%. Myelosuppression was appreciable at this dose and schedule, with 13 patients experiencing life-threatening thrombocytopenia and two drug-related deaths. The level of activity in this disease encourages us to determine a tolerable dose of this drug in combination with cisplatin for further study.
Trans-Basement Membrane Migration of Eosinophils Induced By LPS-Stimulated Neutrophils from Human Peripheral Blood in Vitro
Authors: Kazuyuki Nakagome, Fuyumi Nishihara, Takehito Kobayashi, Toru Noguchi, Tomoyuki Soma, Makoto Nagata
Journal: Journal of Allergy and Clinical Immunology (2016)