tbuckley/cabot-search huggingface dataset:
B-Cell Chronic Lymphocytic Leukemia: A Bird of a Different Feather
Authors: Federico Caligaris-Cappio, Terry J. Hamblin
Journal: Journal of Clinical Oncology (1999)

PURPOSE: To review the recent major advances in the molecular and cell biology of B-cell chronic lymphocytic leukemia (B-CLL). METHODS: We analyzed the nature of malignant B-CLL B cells and their interactions with the microenvironment. RESULTS: B-CLL is a malignancy of a mantle zone-based subpopulation of anergic, self-reactive, activated CD5 + B cells devoted to the production of polyreactive natural autoantibodies. It is the quintessential example of a human malignancy that primarily involves defects in the induction of programmed cell death. An abnormal karyotype is observed in about 50% of patients with B-CLL. Patients with 13q14 abnormalities show heavy somatic mutation and have a benign disease. Trisomy 12 is associated with unmutated VH genes, atypical cellular morphology, and progressive disease. Extended cell survival is further shielded by a kinetic refractoriness likely promoted by abnormalities of the B-cell antigen receptor complex and favored by some cytokines that highlight a reciprocal dialog between malignant B and T cells. Because the tumor cells act as the major accessory cells, the accumulating malignant B-cell population per se is a hurdle to the production of normal antibodies and leads to a progressive and severe hypogammaglobulinemia. Conceivably, in the presence of certain immunoglobulin genes and when the T-cell control becomes deficient, activated malignant B cells may become able to present self-antigens and drive residual normal B cells to produce polyclonal autoantibodies restricted to self-antigens expressed only by blood cells and cause autoimmune cytopenias. CONCLUSION: The distinctiveness of B-CLL B cells explains why B-CLL is different from other B-cell tumors and accounts for the development of immune deficiency and autoimmunity.
Systematic Review of Surgical Management of Nonmetastatic Renal Cell Carcinoma with Vena Caval Thrombus
Authors: Michael Lardas, Fiona Stewart, Duncan Scrimgeour, Fabian Hofmann, Lorenzo Marconi, Saeed Dabestani, Axel Bex, Alessandro Volpe, Steven E. Canfield, Michael Staehler, Milan Hora, Thomas Powles, Axel S. Merseburger, Markus A. Kuczyk, Karim Bensalah, Peter F.A. Mulders, Börje Ljungberg, Thomas B.L. Lam
Journal: European Urology (2015)
Analysis of the prevalence and motivation to smoking among pupils of the Altai region
Authors: E.B. Klester, V.G. Lychev, K.V. Klester
Journal: European Respiratory Journal (2014)

Objective: to study the prevalence and assess the motivation to Smoking at pupils 12-16 years old in the Altai region.  Materials and methods: 2007-2013 was studied relation to smoking at 1577 pupils aged 12 to 16 years; 820 (52%) of boys and 757 (48%) of girls anonymous questionnaire (section of the questionnaire CORSQ (1/M) on the occurrence, duration and intensity of smoking, Fagerstrem9stest to assess the degree of nicotine dependence (ND)).  Results: 569 (66,9%) boys and 423 (55,9%) girls have tried smoking. The main reasons of trying: “the desire to be accepted in the company” - 84,8%; “desire to look more attractive” - 9,5%. The average age of first smoking was8.9±0,11 years. In assessing the motivation ): 85 boys, 64 girls. Age of onset of daily smoking among boys was 11.5±0,1, girls - 12,5±0,04. The duration of smokingwas 3.3±0,04 year. Degree ND: “very weak” - 31%, a “weak” - 21%, “average” - 33%, high - 15% of teens smoking. Motivation to quit smokingat 75% - strong, at 18.8% - average, at 6.2% wasn9t at all.  Conclusions. The prevalence of smoking among teenagers is significant (63%). The main reason of trying smoking is desire to improve their image in the company of their peers. It draws attention to the early initiation of daily smoking, especially among girls, with the formation of high ND at every sixth smoker pupil, which requires inclusion the programs of active psychoprophylaxissmoking in schools and implementation of national strategy for rejection of smoking.
Oral versus intravenous antibiotics
Authors: P. Tsang
Journal: BMJ (1995)

In short, the rates of catheterisation and intubation influence the infection rate in a hospital but are not its only determinant.The rate of puerperal sepsis is related to the birth rate, but that did not stop Semelweiss from trying to eradicate puerperal sepsis.It is nihilistic and inaccurate to suggest that current rates represent an irreducible minimum.Infection control teams should prevent hospital acquired infection through education and promotion of good practices.If some categories of infection are seen as inevitable it will be hard to motivate staff to follow guidelines, standards will fall, and the infection rate will rise.We suggest that most hospital acquired infection is preventable and that infection control teams should continue to try to prevent it.
Redifferentiation of Iodine-Refractory BRAF V600E-Mutant Metastatic Papillary Thyroid Cancer with Dabrafenib—Letter
Authors: Olivier Huillard, Florence Tenenbaum, Jerome Clerc, Francois Goldwasser, Lionel Groussin
Journal: Clinical Cancer Research (2015)

Recently, Rothenberg and colleagues (1) demonstrated that BRAF-specific inhibition with dabrafenib can stimulate radioiodine uptake in patients with metastatic BRAF V600E-mutant iodine-refractory papillary thyroid cancer. This was previously shown with MEK inhibition (2), and growing evidence exist that anticancer therapy will allow restoring radioiodine uptake in radioiodine-resistant or refractory differentiated thyroid cancers (DTC). Although this phenomenon may generate great hope for patients in this setting with unmet needs, the clinical relevance can be questioned and must be determined to help identifying the optimal multimodal therapeutic strategy.In radioiodine-resistant metastatic DTC, the standard-approved treatment is currently sorafenib (3) given until disease progression or unacceptable toxicity. Though currently off label, the specific inhibition of BRAF in BRAF-mutated tumors appears as an interesting first-line option. In effect, dabrafenib is an active and well-tolerated treatment that can even lead to long-term responses (up to 22 months; ref. 4) when given until disease progression or unacceptable toxicity. The study by Rothenberg and colleagues (1) shows that dabrafenib can also restore radioiodine uptake. Dabrafenib could therefore be prescribed for its direct antitumor effect or for its ability to restore radioiodine uptake. But even if radioiodine is an active treatment, radioiodine uptake is not per se an objective because it is not constantly associated with clinical efficacy (5). On the other hand, dabrafenib efficacy may not be limited to lesions in which radioiodine uptake is restored. We therefore believe that the protocol selected by Rothenberg and colleagues with a short course of dabrafenib before radioiodine therapy helps understanding the mechanism of efficacy. Indeed in patients with mixed radioiodine uptake after dabrafenib (i.e., patients having new iodine avid lesions or focal uptake enhancement and other lesions with definitely no uptake), the 3- and 6-month CT evaluation should allow to compare response in lesions according to their final uptake capability. If a better response is seen in lesions with significant radioiodine uptake, a prerequisite for substantial dose delivery, this would be in favor of a multimodal approach in this setting. On the other hand in a same patient, posttherapy (5.5 GBq) thyroglobulin levels are likely to be higher in responding patients due to tumor cells radiolysis or redifferentiation, as compared with diagnostic scan values (0.148 GBq). We wonder if, with the longer follow-up now available, the authors could provide this information.See the Response, p. 5640No potential conflicts of interest were disclosed.
Immune monitoring in patients with colorectal cancer stage II
Authors: Eva Zavadova, Michal Vocka, Jan Spacek, Nicole Francis, Bohuslav Konopasek, Terezie Fucikova, Helena Skalova, Pavel Dundr, Lubos Petruzelka, Tilman T Rau, Carol Geppert, Arndt Hartmann
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Immunoscore has been shown to be a very powerful prognositc indicator in patients with clinically localized colorectal cancer, with no detectable tumour spread to lymph nodes or distant organs. These patients are usually treated with surgical removal of the tumour only. However,
Phase I study of alphaviral vector (AVX701) in colorectal cancer patients: comparison of immune responses in stage III and stage IV patients
Authors: Michael A Morse, Amy Hobeika, William Gwin, Takuya Osada, Jonathan Gelles, Christel Rushing, Donna Niedzwiecki, H Kim Lyerly
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts AVX701 is an alphaviral replicon particle vaccine expressing a modified carcinoembryonic antigen gene (CEA(6D)). We previously reported the preliminary results of a Phase I/II study of AVX701 in metastatic colorectal cancer patients (Morse, J Clin Invest. 2010; 120: 3234–3241).
The effect of Yu-Ping-Feng capsules and Fu-Fang-Dan-Shen tablets on stable COPD
Authors: Min Jie, Mao Bing
Journal: European Respiratory Journal (2013)

Background  In chinese medcine(CM), the method of “Reinforcing Qi and Activating Blood” have already been widely used to treat patients with stable COPD(Qi Deficiency and ‎Blood Stasis Syndrome), but the randomized clinical evidence about that is rare. Yu-Ping-Feng capsules can reinforce Qi and Fu-Fang-Dan-Shen tablets can activate Blood.   Objective  To study the effect of Yu-Ping-Feng capsules and Fu-Fang-Dan-Shen tablets on stable COPD and assesse CM symptoms, laboratory indexes and endpoints.   Method  In a andomized controlled trial, patients in treatment group were given the treatment of Yu-Ping-Feng capsules and Fu-Fang-Dan-Shen tablets for 3 months, and all patients were given conventional treatment. During observation period for 12 months, CM symptoms, cellular immunity indexes and haemodynamics indexes were assessed.   Results  Fifty outpatients were recruited. The CM symptoms in treatment group were improved significantly ( P  P  P  P  P >0.05), while the level of ET was significantly different ( P  P    Conclusion  Yu-Ping-Feng capsules and Fu-Fang-Dan-Shen tablets might be effective in treatment of patients with stable COPD, possibly through improving their cellular immunological function and vasomotor function.
Bloodcurdling movies and measures of coagulation: Fear Factor crossover trial
Authors: Banne Nemeth, Luuk J J Scheres, Willem M Lijfering, Frits R Rosendaal
Journal: BMJ (2015)

<b>Objective</b>&nbsp;To assess whether, as has been hypothesised since medieval times, acute fear can curdle blood. <b>Design</b>&nbsp;Crossover trial. <b>Setting</b>&nbsp;Main meeting room of Leiden University's Department of Clinical Epidemiology, the Netherlands, converted to a makeshift cinema. <b>Participants</b>&nbsp;24 healthy volunteers aged ≤30 years recruited among students, alumni, and employees of the Leiden University Medical Center: 14 were assigned to watch a frightening (horror) movie followed by a non-threatening (educational) movie and 10 to watch the movies in reverse order. The movies were viewed more than a week apart at the same time of day and both lasted approximately 90 minutes. <b>Main outcome measures</b>&nbsp;The primary outcome measures were markers, or "fear factors" of coagulation activity: blood coagulant factor VIII, D-dimer, thrombin-antithrombin complexes, and prothrombin fragments 1+2. The secondary outcome was participant reported fear experienced during each movie using a visual analogue fear scale. <b>Results</b>&nbsp;All participants completed the study. The horror movie was perceived to be more frightening than the educational movie on a visual analogue fear scale (mean difference 5.4, 95% confidence interval 4.7 to 6.1). The difference in factor VIII levels before and after watching the movies was higher for the horror movie than for the educational movie (mean difference of differences 11.1 IU/dL (111 IU/L), 95% confidence interval 1.2 to 21.0 IU/dL). The effect of either movie on levels of thrombin-antithrombin complexes, D-dimer, and prothrombin fragments 1+2 did not differ. <b>Conclusion</b>&nbsp;Frightening (in this case, horror) movies are associated with an increase of blood coagulant factor VIII without actual thrombin formation in young and healthy adults. <b>Trial registration</b>&nbsp;ClinicalTrials.gov NCT02601053.
Guidelines for pharmacological intervention are needed
Authors: E. A Enas
Journal: BMJ (1996)

EDITOR,—Rates of coronary artery disease in young Asian Indians aged under 40 are three to 10 times higher than those in other populations.1 I applaud Sandeep Gupta and colleagues for advocating an “effective campaign of primary prevention” of coronary artery disease in Asian Indians2 but doubt its efficacy unless there is a diligent search for and aggressive treatment of dyslipidaemias.1

Among the one million Asian Indians settled in the United States 27000 are physicians, including 2000 cardiologists. These physicians have made major changes in their lifestyle. In a study of 1478 Asian Indian physicians and their family members in the United States …
The genetic landscape of the T cell non-inflamed tumor microenvironment in human solid tumors
Authors: Jason J Luke, Stefani Spranger, Riyue Bao, Jorge Andrade, Thomas F Gajewski
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts A subset of patients with cancer have evidence of a spontaneous anti-tumor immune response and T cell infiltration into tumor sites. This has prognostic significance and is associated with clinical response to immunotherapeutics in multiple cancers. It has been observed that high
Authors' response
Authors: J. Parkes
Journal: Gut (2011)

Tsochatzis and colleagues1 criticise the methodology used in the analysis of our data and make a comment about the utility of measuring collagen proportionate area (CPA).2 In our analysis, we determine the performance of a continuous variable, the enhanced liver fibrosis (ELF) test score, in predicting clinical outcomes. No attempt was made to convert the ELF score into a virtual histological stage or to relate ELF test scores to histology but both ELF test scores and histology were compared with clinical outcomes as the reference standard. The range of ELF results in the cohort was divided into tertiles and the middle tertile was divided into two groups to create four groups of ELF score. We then determined the …
Scientific Significance of Clinically Insignificant FcγRIIIa-V158F Polymorphism
Authors: Guillaume Cartron, Roch Houot, Holbrook E. Kohrt
Journal: Clinical Cancer Research (2015)

Abstract Kenkre and colleagues report the absence of correlation between FcγRIIIa-V158F polymorphism and rituximab response in follicular lymphoma patients, a result which is in contrast with prior studies. This discrepancy recalls that many other factors (from the host and from the tumor) may influence the efficacy of rituximab in vivo. Clin Cancer Res; 22(4); 787–9. ©2015 AACR. See related article by Kenkre et al., p. 821
Correlation of KRAS status (wild type [wt] vs. mutant [mt]) with efficacy to first-line cetuximab in a study of cetuximab single agent followed by cetuximab + FOLFIRI in patients (pts) with metastatic colorectal cancer (mCRC)
Authors: A. Cervantes, T. Macarulla, E. Martinelli, E. Rodriguez-Braun, F. Ciardiello, C. Stroh, J. Nippgen, J. Baselga, J. Tabernero
Journal: Journal of Clinical Oncology (2008)

4129 Background: KRAS mutation status predicts sensitivity to anti-epidermal growth factor receptor (EGFR) agents in pts with refractory mCRC. In order to assess the efficacy of cetuximab alone and in combination with chemotherapy in the first-line setting, we have analyzed the KRAS mutation status in EGFR-expressing mCRC pts participating in a clinical trial comparing weekly versus bi-weekly administration of cetuximab (Tabernero et al. Proc ASCO 2006). Cetuximab was administered as a first-line single agent for 6 weeks, pts were assessed for response and then FOLFIRI chemotherapy was added to all pts. KRAS mutation status was determined in archived tumor material and its correlation with efficacy parameters evaluated. Methods: Blocks of archived tumor material from 50 pts and paraffin- embedded slide sets from 2 pts were assessed for KRAS mutation analysis eligibility. Genomic DNA was isolated from slides with no prior macrodissection. The KRAS mutation status of codons 12/13 was determined by a highly sensitive quantitative polymerase chain reaction- based assay. Independent histopathologic evaluation revealed that 48/52 samples contained tumor tissue. All 48 pts were fully evaluable for efficacy. Response rate (RR) at end of monotherapy, overall RR during the combination phase (cetuximab + FOLFIRI), and progression-free survival (PFS) time for the 48 pts were determined and correlated with the KRAS status of these pts. Results: KRAS mutations were detected in 19 samples (40%) from the KRAS evaluable population. At the end of the monotherapy phase, RR was 27.6% for the KRAS wt population and 0% for the KRAS mt population (p=0.015). During the combination phase this RR increased to 55.2% vs 31.6%, respectively (p=0.144). PFS for cetuximab + FOLFIRI was significantly improved (hazard ratio: 0.47, p=0.0475) for KRAS wt pts vs KRAS mt pts. Conclusions: KRAS mutation status determines efficacy to cetuximab in the first-line setting of pts with mCRC either alone or when subsequently combined with FOLFIRI. Our findings support that KRAS mutation status should be considered in the choice of therapy in the first- line setting of pts with mCRC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Merck Merck Merck Merck
Association of topoisomerase II-alpha (TOP2A) gene amplification with responsiveness to anthracycline-containing chemotherapy among women with metastatic breast cancer entered in the Herceptin H0648g pivotal clinical trial
Authors: M. F. Press, R. D. Mass, J. Y. Zhou, J. Sullivan-Halley, I. E. Villalobos, G. Lieberman, K. J. Flom, S. Seelig, D. J. Slamon, L. Bernstein
Journal: Journal of Clinical Oncology (2005)

9543 Background: Because approximately 40% of breast cancers with HER2 gene amplification also have amplification of the TOP2A gene and because TOP2A is the known target for anthracyclines, it has been suggested, but not established, that TOP2A gene amplification, not HER2 amplification, may be the predictive marker for responsiveness to anthracycline chemotherapy. Methods: We retrospectively evaluated both HER2 and TOP2A gene amplification in breast cancer tissue from women who were entered in a randomized clinical trial (H0648g) of anthracycline-containing chemotherapy (AC) with or without addition of trastuzumab (Herceptin) immunotherapy. Results: Tissue sections were successfully analyzed for both HER2 and TOP2A gene status for 339 of the 469 (72%) cases originally randomized in the H0648g clinical trial. HER2 was amplified in 279 of 339 (82%) while TOP2A was amplified in 99 of 339 (29%). All cases with TOP2A gene amplification had co-amplification of HER2. Among those women entered to an AC treatment arm, either with or without addition of Herceptin, there was a survival advantage associated with TOP2A gene amplification that did not achieve statistical significance (p = 0.0841). However, analysis of clinical outcome by individual treatment arm demonstrated that for AC patients treated with Herceptin, TOP2A gene amplification did not correlate with outcome; however, in the absence of Herceptin, TOP2A gene amplification was associated with a statistically significant overall survival advantage for those women who were treated with AC alone (p = 0.0147). Conclusions: TOP2A gene amplification in breast cancer tissue is associated with responsiveness to AC chemotherapy in this retrospective analysis of a randomized clinical trial. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech
Histoplasmosis and Sarcoidosis mimicking metastatic disease on FDG positron emission tomography
Authors: M. S. Ahluwalia, V. Dhawan, H. A. Daw
Journal: Journal of Clinical Oncology (2005)

2117 Introduction: Positron emission tomography (PET) has come to play an increasingly important role in the evaluation of cancer patients, both for diagnostic as well as post treatment follow-up. Like other techniques, PET is associated with false positive and negative Results: False positives have been reported in presence of active granulamatous diseases like tuberculosis, aspergillosis, histoplasmosis. We report 2 such cases. Case 1: A 74-year-old male presented with abdominal pain requiring emergency laparotomy that revealed a stricture in jejunum, biopsy of the specimen confirmed diffuse large B cell lymphoma. The patient received CHOP chemotherapy and rituxan. A PET scan performed as treatment follow-up showed progression of the disease in the mediastinum with increased metabolic activity of the lymph node (LN) that had grown in size from 9 mm to 12.5-mm. In addition there were multiple new small LNs in the mediastinum. The patient underwent mediastinoscopy and subsequent biopsy of LN that was negative for malignancy. Further work-up revealed that enlarged LN was due to sarcoidosis. Case 2: A 46-year-old-female with a history of left infiltrating ductal carcinoma of the breast, treated with lumpectomy, radiation and tamoxifen therapy, underwent a follow-up PET scan that showed an anterior pleural based 10x 16 mm nodule in the right middle lobe that demonstrated moderately intense abnormal hypermetabolic activity and 3 hypermetabolic foci present in the right hilum. Differential diagnosis included primary lung carcinoma with right hilar metastasis or metastatic breast cancer. Patient underwent right middle lobe resection that was negative for malignancy. It revealed necrotizing granulomatous inflammation with budding yeast suggestive of histoplasmosis. Conclusion: PET scans play a very important role in the staging of various malignancies and treatment follow-up. However, as demonstrated in these 2 cases, caution should be exercised especially when PET scan findings are used to alter treatment plans. In these situations, tissue diagnosis is mandatory in order to establish accurate diagnosis and avoid potentially toxic therapeutic interventions such as chemotherapy and radiotherapy. No significant financial relationships to disclose.