tbuckley/cabot-search huggingface dataset:
Imatinib mesylate as a preoperative therapy in dermatofibrosarcoma: Results of a multicentric phase II study on 25 patients
Authors: J. Misset, D. Kerob, R. Porcher, O. Verola, S. Dalle, E. Maubec, I. Madelaine-Chambrin, F. Calvo, A. Mathieu-Boue, F. Pedeutour, C. Lebbe
Journal: Journal of Clinical Oncology (2007)

10032 The treatment of dermatofibrosarcoma protuberans (DFSP) relies on a wide local excision with frequent need of reconstructive surgery. A (17,22)translocation with Co1A1-PDGF fusion is present in &gt; 90 % of the cases. Some patient's observations and a report on 9 patients suggest that Imatinib mesylate (IM), targeting PDGFRβ, has a clinical interest in DFSP. The primary aim of this phase II multicentric study was to define the percentage of clinical responders (RECIST) to a preoperative 2 months 600mg IM daily before wide local excision. The secondary goals were to determine tolerance, imaging (ultrasound and MRI), pathological responses and to analyse PDGFRβ phosphorylation status and tumour cell apoptosis in sequential tissues specimen. A flexible design with interim analysis after recruitment of 6 patients was used. 18 to 28 patients had to be enrolled to detect a 30% clinical response rate (relative decrease of tumor of at least 30%) with power 80%, using a one-sided test against 5%, at the 2.5% one-sided level. The interim analysis yielded a clinical response in 3 of 6 patients without severe adverse event. An independent committee advised to continue the trial to obtain a total number of at least 24 patients, in order to reduce the confidence interval of response rate. Twenty-five adults suffering from primary or recurrent DFSP have been included from July 2004 to May 2006, 13F and 12 M, median age 42.4 years [range 23.0–72.5]. Tumour characteristics were as follows: primary (n=20), recurrence (n=5) involving trunk(n=14), head or neck (n=3), limbs (n=6), other n=2; median size was 4.5cm [range 2.4–16]. Translocation t(17;22) was detected in 12 of 12 informative tumours following caryotype or FISH analysis. A clinical response was achieved in 9 (36%) patients(95%CI 18.9–57.5). The median relative decrease of tumor was of 20.0% [range -12.5;100]. Apart from expected grade 1 or 2 side effects, we observed 1 grade 3 neutropenia, 1 grade 3 maculopapular rash and 1 grade 4 transient transaminitis. Imatinib has been recently approved for the treatment of unresectable or metastatic dermatofibrosarcoma. Our results should prompt us to analyse the clinical benefit of a longer duration neoadjuvant treatment for patients with DFSPin order to reduce surgical margins [Table: see text]
Rituximab-induced severe acute thrombocytopenia: A case report and review of literature
Authors: S. Dhand, H. Bahrain
Journal: Journal of Clinical Oncology (2008)

19528 Background: Rituximab, an anti-CD20 monoclonal antibody, is a generally safe and well-tolerated drug. Severe acute thrombocytopenia following administration is a rare phenomenon. Case Report: An 84-year old male with a recent diagnosis of aggressive mantle cell lymphoma was admitted with a mild urinary tract infection. His condition gradually improved and inpatient chemotherapy was begun with R-CHOP. He received a 660 mg rituximab infusion without initial complication. The next day his platelet count had fallen from a pre-infusion level of 121,000/mm3 to 15,000/mm3. There were no signs of hemorrhage and over the course of the next three days the platelet count increased to 24,000. He did not require platelet transfusion and had a marked decrease in his white blood count and lymphadenopathy. The patient was discharged in good condition. Results: A MEDLINE/OVID database search revealed only five previous reported cases of rituximab-induced thrombocytopenia in adults. These included two cases of hairy cell leukemia, two cases of mantle cell lymphoma and one case of prolymphocytic leukemia. Pre-treatment platelet counts ranged from 31,000 to 151,000, and post-treatment counts from 6,000 to 10,000 (mean recorded drop 82,200). Four patients received platelet transfusions. Discussion: Rituximab-induced thrombocytopenia is likely underdiagnosed because most patients do not have blood counts performed the day after treatment. Proposed theories include; (i) CD20 antigen causing antigen-antibody immune-mediated cell lysis by compliment activation, (ii) CD20 antigen on the platelet surface, (iii) platelet binding of a soluble anti-CD20/rituximab complex, and (iv) intravascular fibrinolysis. Interestingly our case and all previously reported cases involved massive bone marrow involvement by neoplastic B-lymphocytes. A large number of patients treated with rituximab will have routine blood counts checked 1 to 2 weeks following therapy and physicians may wrongly attribute thrombocytopenia to the effects of other chemotherapy and make unnecessary dose reductions. Rituximab should therefore be used with caution, especially in those patients with bone marrow involvement. Routine blood counts should be considered soon after therapy to document this potential adverse effect. No significant financial relationships to disclose.
Second-line neoadjuvant chemotherapy (NEO) with cisplatin (C), 5 fluorouracil (5FU) and radiotherapy (XRT) for locally advanced breast (LABC) refractory to anthracyclines: Evaluation after a long-term follow up
Authors: M. F. D. Gaui, R. Salgado, C. G. Ferreira, N. Spector
Journal: Journal of Clinical Oncology (2004)

602 Background: Thirty percent of newly diagnosed breast cancer patients (pts) at INCA are stage III. First-line anthracyclin-based NEO is an effective treatment, but about 30% of the pts will fail. There is no standard second-line rescue treatment for these refractory pts, posing a clinical hurdle. To address that issue from Jan 1994 to Feb 1998 we enrolled pts in a single institution phase II trial of C+5FU+XRT as a rescue treatment. Methods: Sixty LABC inoperable pts considered refractory to anthracyclines after 4 cycles in average, were treated with C 25mg/m2 plus 5-FU 1g/m2 continuous infusion for 4 days, on days 1 and 28. Simultaneous XRT 4500 cGy was applied to the breast. Median age was 48 (29–69), 54% pre- and 46% posmenopausal, and median KPS 90%. Tumor median size (after anthracyclines) was 72cm2 (9 - 646 cm2). Results: Interestingly, after an ITT analyses, 55 pts (91%) were rendered operable (clinical objective response) allowing a mastectomy; 3 pts rejected surgery; 1 was still inoperable and 1 excluded (actual stage IV). The interval between NEO and surgery was in average 58 days. Treatment was well-tolerated and main toxicity was hematological: neutropenia ≥ grade II (8%). Further GI toxicity was 8% (no GIII/IV) and impaired surgical wound healing occurred in 7% of the pts. Median residual tumor was 7cm2 (0–120) and median number of positive nodes was 4 (0–21). Pathological response of the primary tumor was analyzed and 10 pts (16%) showed micro or no residual tumor. Of note, after a median follow-up of 83.5 months (65–117) 10 pts (16%) are alive. Median disease-free survival was 13.9 m (0.8–85) and median overall survival 24 months (1.6- 115). Conclusions: To the best of our knowledge this is the first report of such a high response rate in second-line NEO for anthracyclin-refractory LABC. Our data indicate that the second-line treatment with C+5FU+XRT is an effective, feasible and safe regimen in turning anthracyclin-refractory LABC operable, which is worthy comparing to other taxanes-based regimens. No significant financial relationships to disclose.
Obstructive sleep apnoea as a risk factor for osteopenia and osteoporosis in the male population
Authors: Claudio Liguori, Nicola Biagio Mercuri, Francesca Izzi, Andrea Romigi, Alberto Cordella, Eleonora Piccirilli, Salvatore Viola, Silvio Costa, Paolo Sbraccia, Maria Grazia Marciani, Umberto Tarantino, Fabio Placidi
Journal: European Respiratory Journal (2016)

Obstructive sleep apnoea (OSA) is a sleep disorder characterised by recurrent apnoea events leading to hypoxia, hypercapnia and sleep disruption [1]. OSA represents a growing health problem mainly affecting men; in fact, its prevalence in the adult male population is between 4% and 24% [1–3]. This report proposes the clinical potential of monitoring bone mineral density in male OSA patients <http://ow.ly/Voe47>
Causes and Consequences of Longitudinal LV Dysfunction Assessed by 2D Strain Echocardiography in Cardiac Amyloidosis
Authors: Julien Ternacle, Diane Bodez, Aziz Guellich, Etienne Audureau, Stephane Rappeneau, Pascal Lim, Costin Radu, Soulef Guendouz, Jean-Paul Couetil, Nicole Benhaiem, Luc Hittinger, Jean-Luc Dubois-Randé, Violaine Plante-Bordeneuve, Dania Mohty, Jean-François Deux, Thibaud Damy
Journal: JACC. Cardiovascular imaging (2016)
First-Line Antibiotics May Worsen MRSA infection
Authors: Tracy Hampton
Journal: JAMA (2016)

New research suggests that treatment of Methicillin-resistant Staphylococcus aureus (MRSA) infections with first-line β-lactam antibiotics not only is ineffective but may be harmful (Muller S et al. Cell Host Microbe. 2015;18[5]:520-522).
Oncologists’ discussions of treatment goals and prognosis during clinic visits with African Americans with advanced cancer.
Authors: Susan Eggly, Lauren M. Hamel, Wen-ying Sylvia Chou, Chan L. Thai, David Joseph Debono, Robert Chapman, Terrance Lynn Albrecht, Louis Penner
Journal: Journal of Clinical Oncology (2015)

34 Background: The National Academy of Medicine recommends that cancer patients be informed of their prognosis to enable informed treatment decisions, but research shows few patients receive this information. This problem is greater for minorities, who experience poorer quality clinical communication and end-of-life care relative to white patients. This study describes patient-oncologist discussions about treatment goals/prognosis during clinic visits with African American patients. Methods: Data were from a larger study of communication between African Americans and medical oncologists at two cancer hospitals in Detroit, MI. The present study included video recordings/transcripts of clinic visits with patients with Stage III (n=20) or IV (n=6) cancer and their oncologists (n=9). Two investigators read the transcripts independently to determine whether treatment goals and/or prognosis were mentioned; disagreement was resolved through discussion. Discourse analysis was conducted to describe interactional strategies oncologists used to discuss or avoid discussing these topics. Results: Treatment goals were discussed during most visits (n=24; 92.3%); prognosis was discussed less frequently (n=19; 73.1%). Oncologists often used vague language to describe prognosis (e.g. prognosis is a bit worse in your case). Only one visit included a clear survival estimate. Oncologists used clear language when the goal was cure, but when describing other goals, they often used technical terms (e.g., reduce the risk of recurrence); imprecise terms (e.g., keep the cancer in check); and emphasized uncertainty (e.g., these lesions are suspicious). Oncologists missed opportunities to further explain or elicit patient questions or preferences by directing the discussion to the urgency and details of treatment. Conclusions: Oncologists used ambiguous language to discuss treatment goals/prognosis and missed opportunities to discuss patient perspectives or other options, including palliative care. Interventions are needed to improve communication about these important topics, especially among minority patients with advanced cancer.
Histone deacetylase inhibitors downregulate thymidylate sythnase expression and interact synergistically with fluoropyrimidines in colon cancer cell lines
Authors: William Fazzone, Eva Borucka, Heinz-Josef Lenz, Robert Ladner
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

692 

The foundation for the standard of care for the treatment of advanced colon cancer remains the fluoropyrimidine 5-Fluorouracil (5-FU). 5-FU induces cytotoxicy through multiple pathways, including incorporation of toxic intermediates into DNA and RNA. However, the primary mechanism of action of 5-FU is through inhibition of the enzyme thymidylate synthase (TS), an essential enzyme in DNA synthesis. Expression of TS represents a well-characterized resistance mechanism. Patients bearing tumors that overexpress TS are less likely to respond to 5-FU based chemotherapy. Currently there are no effective chemotherapeutic regimens available to treat advanced colon cancer patients demonstrating TS-mediated resistance. Therefore, drugs that decrease the expression of TS are of continuous clinical interest.

Histone deacetylase inhibitors (HDACi) are a class of novel compounds that have generated a significant amount of interest due to their ability to selectively target cancer cells. This has led to the recent approval suberoylanilide hydroxamic acid (SAHA) for the treatment of cutaneous T-cell lymphoma (CTCL). HDACi have been shown to alter global acetylation patterns in the cell and lead to increased acetylation of both histone and non-histone proteins. Alteration in global acetylation patterns leads to cell cycle arrest, increased apoptosis, and increased differentiation within tumor cells. Previous microarray studies in breast and bladder cancer cell lines have shown that TS gene expression is significantly downregulated by multiple HDACi. We have extended these studies into colon cancer cell lines demonstrating that TS protein and mRNA are significantly downregulated following treatment with a panel of HDACi. Downregulation of TS was shown to be independent of p53, p21, and HDAC2 through the use of cell lines with mutations or absence of these proteins. These observations were extended in vivo whereas TS was shown to be downregulated in HCT116 mouse xenografts by the clinically relevant HDACi SAHA and LBH589. Synergistic interactions on growth inhibition of SAHA with the fluoropyrimidines 5-FU and fluorodeoxyuridine (FUdR) were observed in HCT116 and HT29 cells. Furthermore, depletion of thymidylate pool levels, a mechanistic endpoint of TS inhibition, were enhanced by the combination of SAHA with 5-FU or FUdR in colon cancer cell lines. These results demonstrate that HDACi cause decreases in TS gene expression, and lead to synergistic interactions with fluoropyrimidines. This data suggests a role for combination therapy of HDACi with 5-FU based chemotherapeutic regimens as a strategy to overcome TS-mediated resistance.
Clinical Evaluation of Xpert® BCR-ABL Ultra, an Automated and Standardized Cartridge-Based Assay for the Quantification of BCR-ABL1
Authors: Michael J. Mauro, Richard D. Press, David S. Snyder, Qin Huang, Javier Pinilla-Ibarz, Dahui Qin, Christina Lockwood, Jacqueline E. Payton, Geoffrey L. Uy, Matt E. Kalaycio, Ramon V. Tiu, Vivian Oehler, Gwo-Jen Day, Wendy Wong, Michael P. Bates, Jerald P. Radich
Journal: Blood (2015)
Phase II trial of mitotane and cisplatin in patients with adrenal carcinoma: a Southwest Oncology Group study.
Authors: R M Bukowski, M Wolfe, H S Levine, D E Crawford, R L Stephens, E Gaynor, W G Harker
Journal: Journal of Clinical Oncology (1993)

PURPOSE Previous reports of chemotherapy in patients with adrenal cancer have described responses to cisplatin (CDDP). Because of these reports of good results, a phase II trial that used CDDP with and without mitotane (o,p'DDD) was initiated. PATIENTS AND METHODS Patients with metastatic or residual adrenocortical carcinoma with objectively measurable disease or biochemical abnormalities were divided into good-risk and poor-risk categories. The latter received CDDP 100 mg/m2 intravenously, and the former received 75 mg/m2. o,p'DDD was administered at a 1,000-mg dose orally four times a day along with cortisone acetate and Florinef (fludrocortisone acetate; Bristol-Myers Squibb Co, Princeton, NJ). RESULTS Of a total of 42 patients entered onto the study, 37 were eligible. Twenty-nine patients received good-risk and eight received poor-risk doses of CDDP. Functioning tumors were present in 45% of patients. Objective responses were noted in 30% (11 of 37) patients (95% confidence interval, 16% to 50%). Response duration was 7.9 months, and the median time to response was 76 days. The median survival of the 37 eligible patients was 11.8 months, and a significant survival advantage was found for patients who underwent prior surgical removal of their primary tumor or bulky disease, who had a performance status of 0 or 1, or who had synchronous metastatic disease. Toxicity of the CDDP and o,p'DDD combination was moderate to severe, and the most common side effects were gastrointestinal, renal, and neurologic. CONCLUSION The regimen of CDDP and o,p'DDD has activity in patients with adrenocortical carcinoma; however, the toxicity of this treatment was moderate to severe.
Inhibition of STAT3 driven gene expression in melanoma cells by SCV-07
Authors: V. Nagabhushanam, K. Subbarao, M. Ramachandran, J. Reddy, C. Tuthill
Journal: Journal of Clinical Oncology (2008)

14619 Introduction: Agents that boost the immune response to overcome tumor-induced immunosuppression have taken center stage in the treatment of various cancers. The di-peptide, SCV-07 (γ-glutamyl-tryptophan) has had success in reducing progression of renal and lung carcinoma as well as melanoma (Effect of the immune modulating peptide, SCV-07, in the murine B16 melanoma model J of Clin Onc, 2007 ASCO Ann. Meeting Proc. Part I. Vol 25, No. 18S (June 20 Suppl), 2007: 13514) in mouse models. SCV-07 is also capable of inducing a Th1 response, evidenced by increased levels of IL-2 and IFNγ (Biological Activity of Peptide SCV-07 Against Murine Tuberculosis Russian J of Immunol, 2003. Vol 8(1): 11). The action of SCV-07 is independent of antigen-specificity and appears to have a global effect on the immune system. Since it is known that STAT3 is upregulated in the tumor micro-environment and that STAT3 driven gene products inhibit the immune response, the following studies were conducted to determine whether the immune-boosting effect of SCV-07 can be attributed to an effect on STAT3 reduction, thereby relieving immunosuppression and enhancing anti-tumor immune responses. Methods: B16F0 melanoma cells were transiently transfected with a STAT3 responsive element driving luciferase expression and then exposed to SCV-07 to determine the effect of the peptide on STAT3 responsive genes. The effect of SCV-07 on nuclear translocation of phosphorylated STAT3 in IL-6 treated HeLa cells was examined by immunofluorescence staining. Results: SCV-07 inhibits the expression of STAT3 responsive genes to the extent of 60–70%. This effect is seen across a range of concentrations. The di-peptide also appears to inhibit the nuclear translocation of phophorylated STAT3. It is not certain as yet whether this is due to direct binding of the peptide to STAT3 or an indirect mechanism. Conclusions: STAT3 expression in tumor cells has been known to be responsible for progression of tumor growth, expression of suppressive cytokines and general inhibition of a protective immune response. Here we show that a di-peptide with known effect against melanoma progression in a mouse model inhibits STAT3 driven gene expression. This is therefore a likely mechanism by which SCV-07 boosts the immune system to relieve tumor-induced immunosuppression. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration SciClone Pharmaceuticals SciClone Pharmaceuticals Inc
The MEST score provides earlier risk prediction in lgA nephropathy
Authors: Sean J. Barbour, Gabriela Espino-Hernandez, Heather N. Reich, Rosanna Coppo, Ian S.D. Roberts, John Feehally, Andrew M. Herzenberg, Daniel C. Cattran, N. Bavbek, T. Cook, S. Troyanov, C. Alpers, A. Amore, J. Barratt, F. Berthoux, S. Bonsib, J. Bruijn, V. D’Agati, G. D’Amico, S. Emancipator, F. Emmal, F. Ferrario, F. Fervenza, S. Florquin, A. Fogo, C. Geddes, H. Groene, M. Haas, P. Hill, R. Hogg, S. Hsu, T. Hunley, M. Hladunewich, C. Jennette, K. Joh, B. Julian, T. Kawamura, F. Lai, C. Leung, L. Li, P. Li, Z. Liu, A. Massat, B. Mackinnon, S. Mezzano, F. Schena, Y. Tomino, P. Walker, H. Wang, J. Weening, N. Yoshikawa, H. Zhang, R. Coppo, S. Troyanov, D.C. Cattran, H.T. Cook, J. Feehally, I. Roberts, V. Tesar, D. Maixnerova, S. Lundberg, L. Gesualdo, F. Emma, L. Fuiano, G. Beltrame, C. Rollino, None RC, A. Amore, R. Camilla, L. Peruzzi, M. Praga, S. Feriozzi, R. Polci, G. Segoloni, L. Colla, A. Pani, A. Angioi, L. Piras, None JF, G. Cancarini, S. Ravera, M. Durlik, E. Moggia, J. Ballarin, S. Di Giulio, F. Pugliese, I. Serriello, Y. Caliskan, M. Sever, I. Kilicaslan, F. Locatelli, L. Del Vecchio, J.F.M. Wetzels, H. Peters, U. Berg, F. Carvalho, A.C. da Costa Ferreira, M. Maggio, A. Wiecek, M. Ots-Rosenberg, R. Magistroni, R. Topaloglu, Y. Bilginer, M. D’Amico, M. Stangou, F. Giacchino, D. Goumenos, P. Kalliakmani, M. Gerolymos, K. Galesic, C. Geddes, K. Siamopoulos, O. Balafa, M. Galliani, P. Stratta, M. Quaglia, R. Bergia, R. Cravero, M. Salvadori, L. Cirami, B. Fellstrom, H. Kloster Smerud, F. Ferrario, T. Stellato, J. Egido, C. Martin, J. Floege, F. Eitner, A. Lupo, P. Bernich, P. Menè, M. Morosetti, C. van Kooten, T. Rabelink, M.E.J. Reinders, J.M. Boria Grinyo, S. Cusinato, L. Benozzi, S. Savoldi, C. Licata, M. Mizerska-Wasiak, G. Martina, A. Messuerotti, A. Dal Canton, C. Esposito, C. Migotto, G. Triolo, F. Mariano, C. Pozzi, R. Boero, S. Bellur, G. Mazzucco, C. Giannakakis, E. Honsova, B. Sundelin, A.M. Di Palma, F. Ferrario, E. Gutiérrez, A.M. Asunis, J. Barratt, R. Tardanico, A. Perkowska-Ptasinska, J. Arce Terroba, M. Fortunato, A. Pantzaki, Y. Ozluk, E. Steenbergen, M. Soderberg, Z. Riispere, L. Furci, D. Orhan, D. Kipgen, D. Casartelli, D. Galesic Ljubanovic, H. Gakiopoulou, E. Bertoni, P. Cannata Ortiz, H. Karkoszka, H.J. Groene, A. Stoppacciaro, I. Bajema, J. Bruijn, X. Fulladosa Oliveras, J. Maldyk, E. Ioachim
Journal: Kidney International (2015)
Clinical features and results of therapy for children with paraspinal soft tissue sarcoma: a report of the Intergroup Rhabdomyosarcoma Study.
Authors: J A Ortega, M Wharam, E A Gehan, A H Ragab, W Crist, B Webber, E S Wiener, V Haeberlen, H M Maurer
Journal: Journal of Clinical Oncology (1991)

Soft tissue sarcomas of the paraspinal region comprised 3.3% (56 of 1,688) of the patients entered and eligible on Intergroup Rhabdomyosarcoma Studies I (IRS-I) and II (IRS-II) (1972 to 1984). These lesions tended to be greater than 5 cm in diameter at diagnosis, invaded the spinal extradural space, and were of the extraosseous Ewing's sarcoma or undifferentiated sarcoma subtype in 55% (30 of 56) of the cases. Patients with tumors in clinical groups II, III, and IV were treated with radiotherapy (XRT) and vincristine-dactinomycin (VA) or VA plus cyclophosphamide (VAC) +/- doxorubicin. Clinical group I patients treated on IRS-II did not receive XRT, while those on IRS-I were randomized to receive VAC +/- XRT. Forty-four of the paraspinal patients (79%) achieved a complete response (CR) compared with 77% (1,260 of 1,632) for patients with disease in other sites. Twenty-seven patients (55%) subsequently relapsed (five local, three regional, four local and distant, and 14 distant). The proportion of patients surviving 5 years by clinical group (stage) from I to IV were 50%, 50%, 62%, and 27%, respectively. Paraspinal patients had somewhat poorer survival than patients with disease in other sites, both in IRS-I and IRS-II; the percentage of paraspinal patients surviving 5 years was 50% and 52% for IRS-I and IRS-II, respectively, whereas these percentages were 55% and 63% for patients with disease in other sites. Histology did not influence the CR rate, but unexpectedly, patients who had embryonal rhabdomyosarcoma (RMS) had the poorest overall survival rate. We concluded that patients with paraspinal lesions may require extended-field radiation therapy to reduce the high local failure rate and more intensive chemotherapy to achieve better local and systemic tumor control.