tbuckley/cabot-search huggingface dataset:
Orchiectomy alone in the treatment of clinical stage I nonseminomatous germ cell tumor of the testis.
Authors: P C Sogani, W F Whitmore, H W Herr, G J Bosl, R B Golbey, R C Watson, J J DeCosse
Journal: Journal of Clinical Oncology (1984)

Forty-five patients with clinical stage I nonseminomatous germ cell tumor of the testis (NSGCTT) were entered in a prospective clinical trial to receive no treatment other than orchiectomy until clinical evidence of relapse. Of this group, 36 patients (80%) have been continuously free of disease for a median duration of 19.5 months after orchiectomy. Nine patients (20%) have relapsed, eight within seven months of orchiectomy. Seven of nine relapsing patients have been rendered free of disease with chemotherapy and/or surgery for a median duration of seven months (range, one to 33 months) after completion of treatment; the other two patients are presently under treatment although one has progressive disease. The relapse rate was higher in patients with embryonal carcinoma than in those with teratocarcinoma, 57% versus 17%. These preliminary results imply that the omission of routine lymphadenectomy or lymph-node irradiation in clinical stage I NSGCTT deserves further trial.
Adjuvant ovarian suppression combined with tamoxifen or anastrozole, alone or in combination with zoledronic acid, in premenopausal women with hormone-responsive, stage I and II breast cancer: First efficacy results from ABCSG-12.
Authors: M. Gnant, B. Mlineritsch, W. Schippinger, G. Luschin-Ebengreuth, S. Poestlberger, C. Menzel, R. Jakesz, E. Kubista, C. Marth, R. Greil
Journal: Journal of Clinical Oncology (2008)

LBA4 Background: Zoledronic acid (ZOL) has demonstrated antitumor and antimetastatic activity in preclinical and early clinical studies. The Austrian Breast and Colorectal Cancer Study Group Trial 12 (ABCSG-12) examined the efficacy of ovarian suppression using the gonadotropin-releasing hormone analogue goserelin in combination with anastrozole (ANA) or tamoxifen (TAM) ± ZOL in premenopausal women with endocrine-responsive breast cancer (BC). Methods: 1801 premenopausal women with endocrine-responsive BC were randomized to goserelin (3.6 mg q 28 d SC) and TAM (20 mg/d PO) ± ZOL (4 mg IV q 6 mo) or goserelin and ANA (1 mg/d PO) ± ZOL for 3 yr. Primary endpoint was disease-free survival (DFS) for both the comparison of TAM vs ANA and ZOL vs no ZOL, respectively. Relapse-free survival (RFS) and overall survival (OS) were secondary endpoints. Exploratory endpoints included bone-metastases-free survival and safety. Results: With median follow-up of 60 mo (March 31, 2008), 137 (7.6%) DFS events and 42 (2.3%) deaths have occurred. There was no significant difference in DFS between patients who received TAM alone vs ANA alone (HR = 1.10 [95% CI = 0.79, 1.54]; P = .59). However, endocrine therapy plus ZOL significantly reduced the risk of DFS events by 36% compared with endocrine therapy alone (HR = 0.64 [0.46, 0.91]; P = .01). The addition of ZOL significantly reduced the risk of RFS events by 35% (HR = 0.65 [0.46, 0.92]; P = .015) compared with endocrine therapy alone. For OS, there was a nonsignificant trend favoring ZOL treatment (HR = 0.60 [0.32, 1.11]; P = .10). Treatment was generally well tolerated among the 4 groups and consistent with known safety profiles of the drugs. Conclusions: There was no significant difference in DFS between TAM and ANA. The addition of ZOL (4 mg q 6 mo) to adjuvant endocrine therapy significantly prolonged DFS and RFS compared with adjuvant endocrine therapy alone in premenopausal women with endocrine-responsive BC. This large clinical trial demonstrates that the antitumor activity of adjuvant ZOL improves outcomes beyond the effect of endocrine therapy alone. No significant financial relationships to disclose.
Epigenetic alteration of BRCA1 in human ovarian tumors
Authors: K. Takehara, K. Miyamoto, Y. Kawakami, M. Kumagai, O. Samura, M. Egawa, H. Nakamura, T. Mizunoe, K. Taniyama, F. Saji
Journal: Journal of Clinical Oncology (2009)

e16532 Background: The breast cancer susceptibility gene 1 (BRCA1) is mutated in half of hereditary breast cancers, and in about 80% of hereditary breast and ovarian cancers. Also, BRCA1 expression is decreased in sporadic breast cancers by other mechanisms, such as epigenetic alteration, suggesting its important role in sporadic breast cancers. The epigenetic alteration of BRCA1 and its contribution in sporadic ovarian tumors are not fully understood. Methods: We evaluated the DNA methylation status of the BRCA1 5’ CpG island by methylation-specific PCR in 12 human ovarian cancer cell lines and 39 primary epithelial ovarian tumor specimens. Cases included the following: malignant (n = 16), borderline (n = 8), and benign (n = 16) tumors. The correlation between these results and clinicopathological features was examined. Results: BRCA1 was hypermethylated in one of 12 (8%) ovarian cancer cell lines and 15 of 39 (38%) primary ovarian tumors. Relative to clinicopathological features, BRCA1 methylation was detected in 39% of malignant and borderline tumors and in 38% of benign tumors, suggesting the importance of BRCA1 pathway in both types of tumors. Some adjacent nontumorous tissues also showed aberrant methylation. Conclusions: BRCA1 was found to be frequently hypermethylated both in benign and malignant ovarian tumors. Our results suggest that epigenetic alteration of BRCA1 might play a role in the development of benign and malignant sporadic ovarian tumors. No significant financial relationships to disclose.
WHO urges countries in dengue belt to look out for Zika
Authors: Anne Gulland
Journal: BMJ (2016)

Thank you for your interest in spreading the word about The BMJ.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Username * Your Email * Send To * You are going to email the following WHO urges countries in dengue belt to look out for Zika Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Detection of mutant-free circulating tumor DNA in the plasma of patients with gastrointestinal stromal tumor (GIST) harboring activating mutations of C-Kit or PDGFRA.
Authors: Nikolas von Bubnoff, Irina Kerle, Katja Specht, Melanie Bruegel, Claudia Wickenhauser, Philipp Jost, Dietger Niederwieser, Christian Peschel, Justus Duyster, Thoralf Lange, Jacqueline Maier
Journal: Journal of Clinical Oncology (2013)

10508 Background: In gastrointestinal stromal tumor (GIST), there is no biomarker available that indicates success or failure of therapy. We hypothesized that tumor specific CKIT or PDGFRA mutant DNA fragments can be detected and quantified in plasma samples of GIST patients. Methods: We prospectively collected 291 plasma samples from 38 subjects with GIST harbouring activating mutations of CKIT or PDGFRA detected in tumor tissue, irrespective of current disease status or treatment. We used allele-specific Ligation PCR to detect mutant free circulating (fc)DNA. Results: We were able to detect fcDNA harbouring the tumor mutation in 15 out of 38 patients. Patients with active disease displayed significantly higher amounts of mutant fcDNA compared to patients in CR. The amount of mutant fcDNA correlated with disease course. We observed repeated positive test results or an increase of mutant fcDNA in five patients with progressive disease or relapse. A decline of tumor fcDNA or conversion from positive to negative was seen in five patients responding to treatment. A negative to positive conversion was seen in two patients with relapse and one patient with progression. In two cases, we aimed to identify additional mutations, and found four additional exchanges, including mutations not known from sequentially performed tumor biopsies. Conclusions: Our results indicate that free circulating DNA harbouring tumor specific mutations in the plasma of patients with GIST can be used as tumor-specific biomarker. The detection of resistance mutations in plasma samples might allow earlier treatment changes and obviates the need for repeated tumor biopsies. Clinical trial information: NCT01462994.
Randomized phase II trial of first-line treatment with sorafenib versus interferon in patients with advanced renal cell carcinoma: Final results
Authors: C. Szczylik, T. Demkow, M. Staehler, F. Rolland, S. Negrier, T. E. Hutson, R. M. Bukowski, U. J. Scheuring, K. Burk, B. Escudier
Journal: Journal of Clinical Oncology (2007)

5025 Background: This trial investigated the efficacy and safety of sorafenib (SOR) vs interferon (IFN) in treatment-naïve patients with clear-cell renal cell carcinoma (RCC). Methods: Previously untreated patients with advanced RCC were randomized to continuous oral SOR 400 mg bid or IFN 9 million units tiw (part 1), with an option of dose escalation to SOR 600 mg bid or crossover from IFN to SOR 400 mg bid upon disease progression (part 2). The primary endpoint was progression-free survival (PFS). Results: Baseline characteristics (ITT, n=189) were similar in SOR (n=97) and IFN (n=92) groups. In the IFN arm, 90/92 patients received treatment; 56 had disease progression, of which 50 crossed to SOR. All 97 patients in the SOR arm received SOR 400 mg bid; 65 had disease progression, of which 44 were dose escalated to 600 mg bid. In part 1, 5% vs 9% patients had complete/partial response, disease control rate (complete/partial response + stable disease) was 79% vs 64%, and median PFS was 5.7 months (CI: 5.0–7.4 months) vs 5.6 months (CI: 3.7–7.4 months) for SOR vs IFN, respectively. Progression-free rates for SOR vs IFN were 90.0% vs 70.4%, 45.9% vs 46.5%, and 11.5% vs 30.4% at 3, 6, and 12 months, respectively. A total of 11% vs 15% of patients receiving SOR or IFN, respectively, discontinued due to adverse events. Overall, the incidence of adverse events was similar between both treatment arms, although skin toxicity (rash and hand-foot skin reaction) and diarrhea occurred more frequently in the SOR group, and flu-like syndrome occurred more frequently in the IFN group. In part 2, median PFS was 5.3 months (CI: 3.6–6.1 months) in patients (n=50) who crossed from IFN to SOR. The median PFS for patients (n=44) with dose escalation to 600 mg bid was 3.6 months (CI: 1.9–5.3 months). The 600 mg bid dose was well tolerated. Conclusions: Although the primary endpoint (PFS) was not reached, SOR showed activity in first-line treatment of RCC based on disease control rate. PFS benefit was observed in patients who crossed to SOR 400 mg bid after progression on IFN. Patients who were dose escalated to 600 mg bid after progression had disease stabilization for a further 3.6 months. Further analyses of possible benefit from SOR dose escalation are required in a larger number of patients. [Table: see text]
Phase I trial of dacarbazine with cyclophosphamide, carmustine, etoposide, and autologous stem-cell transplantation in patients with lymphoma and multiple myeloma.
Authors: D R Adkins, D Salzman, D Boldt, J Kuhn, R Irvin, G D Roodman, R Lyons, L Smith, C O Freytes, C F LeMaistre
Journal: Journal of Clinical Oncology (1994)

PURPOSE We investigated the feasibility of escalating doses of dacarbazine (DTIC) in combination with high-dose cyclophosphamide, carmustine, and etoposide (CBV) given with autologous stem-cell transplantation in 33 patients with relapsed or refractory lymphoma or multiple myeloma. PATIENTS AND METHODS Eligible patients were treated in this phase I study with cyclophosphamide (7.2 g/m2), carmustine (BCNU) (600 mg/m2), etoposide (2.4 g/m2), and escalating doses of DTIC (3,000 to 6,591 mg/m2) administered either as a 2- (in 23 patients) or a 6- (in 10 patients) hour infusion to determine the maximum-tolerated dose (MTD) of DTIC and the toxicity profile of this combination. RESULTS The MTD of DTIC infused over 2 hours and given with the CBV regimen was 3,900 mg/m2, with the dose-limiting toxicity being hypotension. Seven patients experienced transient acute hypocalcemia in association with the DTIC infusion. Prolonging the DTIC infusion to 6 hours or administration of supplemental calcium did not allow further dose escalation of DTIC to occur. Other non-hematologic toxicities observed with this regimen have been reported with CBV alone. Of 25 patients assessable for tumor response at first evaluation posttransplant, 13 (52%) were in complete remission (CR), four (16%) were in partial remission (PR), five (20%) had stable disease (SD), and three (12%) had progressive disease (PROG). Of 31 patients assessable for relapse-free survival, 22 are alive with 13 in CR, one in PR, two with SD, and six with PROG at a median follow-up duration of 313 days (range, 35 to 749+). Treatment-related mortality occurred in six patients (18%). CONCLUSION The feasibility of combining DTIC in high doses with the CBV regimen has been demonstrated. Dose-limiting hypotension is transient and reversible when DTIC is administered at 3,900 mg/m2 with CBV. Future trials to evaluate the effect of the addition of DTIC to the CBV regimen on response rate and relapse-free survival are encouraged.
Phase I trial of romidepsin, a histone deacetylase inhibitor, given on days one, three and five in patients with thyroid and other advanced cancers
Authors: R. Piekarz, V. Luchenko, D. Draper, J. J. Wright, W. D. Figg, A. T. Fojo, S. E. Bates
Journal: Journal of Clinical Oncology (2008)

3571 Background: Romidepsin (FK228 or depsipeptide) is a potent histone deacetylase inhibitor (HDI) with cytotoxic activity in preclinical models and significant activity in patients with cutaneous and peripheral T-cell lymphoma. As responses have been infrequently observed in solid tumors it is important to test HDIs in combination therapy. One strategy is to use HDIs to induce expression of genes that can be targeted therapeutically. Metastatic thyroid cancer refractory to RAI offers one such opportunity. In vitro, HDIs restore expression of the sodium iodine symporter in refractory cells and sensitivity to RAI. Methods: We initiated a phase I trial of romidepsin in a new schedule, administered on days 1, 3 and 5 with the goal of enhancing gene expression and evaluating RAI uptake in patients with RAI-refractory thyroid cancer. Results: We have completed the dose escalation stage of the protocol with 26 patients with solid tumors enrolled, including 9 patients with thyroid cancer. Doses tested were 1, 2, 3.3, 5, 7, 9 mg/m2. Patients received a median of 2.5 cycles (1–24); those with thyroid cancer a median of 8 (range 1–24). Twelve of 19 patients treated on the first 5 dose levels tolerated drug well enough to have the dose escalated. Two patients experienced DLTs, one patient with pulmonary metastasis at the 2 mg/m2 experienced worsening hypoxia associated with atrial fibrillation and another at 9 mg/m2 had refractory grade 3 nausea and vomiting. No grade 4 toxicities were observed. Grade 3 toxicities included leucopenia (2), lymphopenia (4), granulocytopenia (2), thrombocytopenia (2), anorexia (4), nausea (3), and vomiting (2). Based on observed toxicities, we concluded that 9 mg/m2 represented the MTD on this schedule. Eleven patients had stable disease, median 28 wks; 6 with thyroid cancer, median 33 wks. Four patients with RAI refractory thyroid cancer have undergone follow up diagnostic RAI scans; none had increased RAI uptake. Evaluation of histone acetylation in PBMCs demonstrated a greater than 2-fold increase even at dose levels well below the MTD. Conclusions: The MTD was reached on a new schedule of romidepsin administered on days 1, 3, and 5; this protocol is now exclusively evaluating patients with non-medullary thyroid cancer. No significant financial relationships to disclose.
P0455 : IL-4Ra oegulates liver fibrosis differently during progression and reversal phases by modulating the ratio of M1 vs M2 macrophages
Authors: S.-Y. Weng, S. Vijayan, X.-Y. Wang, Y. Tang, K. Padberg, Y.O. Kim, F. Brombacher, J. Crosby, M. McCaleb, A. Waisman, D. Schuppan
Journal: Journal of Hepatology (2015)
Pool Size of Pluripotential Hematopoietic Stem Cells Increased in Continuous Bone Marrow Culture by Friend Spleen Focus-Forming Virus&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;
Authors: J S Greenberger, N Hoffman, M Lieberman, L E Botnick, M A Sakakeeny, R J Eckner
Journal: JNCI Journal of the National Cancer Institute (1983)

Continuous mouse bone marrow cultures were infected with Friend murine leukemia virus. Production of nonadherent (NA) and adherent cells, granulocyte-macrophage colony-forming unil(s) of progenitor cells (GM-CFUc), pluripotential hematopoietic stem cells (CFUs), the self-renewal potential (Rs) of CFUs, and generation of factor-dependent (FD) multipotenlial and committed permanent stem cell cloned lines were measured. Uninfected marrow cultures from C57BL/6J, C57BL/6JUt, B6.S, C3H/HeJ, (C57BL/6J × DBA/2J)F1, CD-1 Swiss, or N:NIH(S) mice generated NA cells, GM-CFUc, and CFUs for 20–41 weeks; cultures infected with Rauscher or other helper viruses generated them for 35–45 weeks. GM-CFUc and CFUs production in SFFV-positive cultures persisted for over 65 weeks and exceeded control levels by twentyfold to fiflyfold. The Rs of CFUs in SFFV-positive cultures was not detectably increased above control cultures. Multipotential (erythroid-neutrophil-mast cell-basophil-eosinophil) permanent FD cell clones were derived from control and SFFV-positive cultures. Thus SFFV amplifies the stem cell pool in vitro without detectably increasing the Rs capacity of CFUs.
Thousands die in clinical trials in India, but compensation is rarely paid
Authors: S. Bagcchi
Journal: BMJ (2015)

Around 2209 people have died in clinical trials in India since 2011, figures released by the office of the Drug Controller General of India have shown. 

The figures, which go up to 20 October 2015, included 1335 deaths since January 2013. They were released as a right to information response on 17 September.

Death during clinical trials in India is a longstanding problem …
Long term effects of traffic noise on chronic obstructive pulmonary disease (COPD) mortality in the Barcelona Metropolitan Region, 2004-2007
Authors: Aurelio Tobias, Diego Varga, Maria Barcelo, Julio Díaz, Marc Saez
Journal: European Respiratory Journal (2014)

Several studies have found an association between traffic noise and adverse health effects, both, morbidity and mortality. Some authors question these because of the high association between traffic noise and air pollution. However, recently several studies have shown an independent short-term association between noise and cardiovascular and respiratory mortality from the effect of air pollutants that are routinely measured.  Our objective here is to provide evidence of an independent long-term association between traffic noise and mortality due to COPD.  We used a case-control design with individual data. Ascases, we use deaths fromCOPD (for which we georeferencedtheir address)between 2004 and2007 inthe Barcelona Metropolitan Region (BMR), Spain. As controls, we used deaths byAIDSand external causes, matched by sex and age. We used the annual mean of daytime noise level for RGM and controlled for confounders: i) air pollutants (NO 2 , PM 10  and benzene); material deprivation (at a census tract level); and several land use variables. We explicitly controlled for spatial misalignment (i.e. the response and all the exposure measurements had different spatial locations); heterogeneity; and spatio-temporal dependency. Analyses were done separately for men and for women.  We estimated a risk increase of COPD mortality of 6.01% (95CI 3.76%-8.17%) for an increased annual mean of daytime interquartile range 7.613 dB(A). This risk was not confounded by any variable. No effect was found for women and for subjects aged   Our results suggest that the associations indicating the long-term effects of exposure to traffic noise are not spurious.
Taking the patient’s body surface area into account when estimating GFR
Authors: Kit Byatt
Journal: BMJ (2016)

Ellam and colleagues’ article is timely.1 As a geriatrician, I have been exercised by this topic since its inception. The estimated glomerular filtration rate (GFR) is of no great help prognostically in older patients and its apparent simplicity can mislead. Many doctors just see “GFR of 62 mL/min” …
Key Role of α-Toxin in Fatal Pneumonia Caused by <i>Staphylococcus aureus</i> Sequence Type 398
Authors: Mariana F. Bonesso, Anthony J. Yeh, Amer E. Villaruz, Hwang-Soo Joo, Joshua McCausland, Carlos M. C. B. Fortaleza, Ricardo S. Cavalcante, Moises T. Sobrinho, Carlos F. Ronchi, Gordon Y. C. Cheung, Maria L. R. S. Cunha, Michael Otto
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

such as hypoventilation and hypereosinophilic syndrome is surprising, and we propose that these findings may indicate novel functions for these gene products relevant to the pathogenesis of lung disease in smokers, a concept that requires further study.Our study has limitations.Subsequent functional investigation is needed to determine how these genes may contribute to the pathogenesis of complex, smoking-related acquired lung disease.This is especially true for genes whereby loss-of-function mutations are implicated in the lung disorder but were up-regulated in healthy smokers in this study.In addition, only a subset of samples were confirmed by RNA sequencing.Bearing these limitations in mind, the data support the concept that genes implicated in rare monogenic lung diseases may have roles in the pathogenesis of smoking-related lung diseases and that smoking-induced changes in expression of these genes could be early molecular events in the development of diverse smoking-related clinical phenotypes.
Nursing aides and patient violence
Authors: P Levy, P Hartocollis
Journal: American Journal of Psychiatry (1976)

The authors studied the incidence of violence in a psychiatric unit organized as a therapeutic community whose nursing staff was composed entirely of women in comparison with another unit staffed according to the traditional male and female nursing pattern. The unit staffed by women had no incidents of other-directed violence in the one-year period of the study, but the traditionally staffed unit had 13 violent incidents initiated by 5 patients. The authors state that the expectation of violence among psychiatric patients and the consequent use of male nursing aides to control violence may represent a self-fulfilling prophecy.