tbuckley/cabot-search huggingface dataset:
Single-Cell Sequencing for Precise Cancer Research: Progress and Prospects
Authors: Xiaoyan Zhang, Sadie L. Marjani, Zhaoyang Hu, Sherman M. Weissman, Xinghua Pan, Shixiu Wu
Journal: Cancer Research (2016)

Advances in genomic technology have enabled the faithful detection and measurement of mutations and the gene expression profile of cancer cells at the single-cell level. Recently, several single-cell sequencing methods have been developed that permit the comprehensive and precise analysis of the cancer-cell genome, transcriptome, and epigenome. The use of these methods to analyze cancer cells has led to a series of unanticipated discoveries, such as the high heterogeneity and stochastic changes in cancer-cell populations, the new driver mutations and the complicated clonal evolution mechanisms, and the novel identification of biomarkers of variant tumors. These methods and the knowledge gained from their utilization could potentially improve the early detection and monitoring of rare cancer cells, such as circulating tumor cells and disseminated tumor cells, and promote the development of personalized and highly precise cancer therapy. Here, we discuss the current methods for single cancer-cell sequencing, with a strong focus on those practically used or potentially valuable in cancer research, including single-cell isolation, whole genome and transcriptome amplification, epigenome profiling, multi-dimensional sequencing, and next-generation sequencing and analysis. We also examine the current applications, challenges, and prospects of single cancer-cell sequencing.
High dose rate brachytherapy with surface applicators: Treatment for nonmelanomatous skin cancer
Authors: J. Musmacher, M. Ghaly, K. Satchwill
Journal: Journal of Clinical Oncology (2006)

15543 Background: To assess the use of HDR surface applicators as an alternative radiotherapy modality to external radiation (electrons or low-energy x-rays) for the treatment of skin lesions of the head and neck. Skin carcinomas require efficient and accurate delivery of HDR Brachytherapy, which can be precisely reproduced on an outpatient basis. Methods: Patients were treated to various sites, which included lesions of the face and scalp. Thermoplastic casts were fitted with Leipzig Surface Applicators and custom molded to the patient to treat squamous or basal cell carcinomas ≤ 2 cm in diameter. A custom surface mold applicator (Freiburg Flap) was used for lesions up to 4 cm. Planning target volume included the tumor plus a 5 mm margin. Biweekly photographs of the treatment volume were taken for documentation and monitoring of radiation reactions. Treatment was delivered by HDR Brachytherapy (Ir-192), 5 Gy per fraction, twice per week for four weeks to a 5 mm depth. TLD’s were placed at the center of the treated volume under the applicator and at critical structures (i.e. lateral canthus of the ipsilateral eye, auditory canal or gingivolabial sulcus) twice during the course of treatment. Results: Patients’ setup and reproducibility were accurate and treatment time was short which added great convenience for the patients. With the HDR surface applicators, dose distribution was uniform in the surface of the skin and at 5 mm depth in the whole area of the applicator. Differences between the areas of maximum and minimum dose at this depth did not reach values higher than 5% of the prescribed dose. At the edges of the applicators, the dose gradient was sharp, with the detected dose at 5 mm from the applicator being negligible. An exudative radiation reaction was noted in some patients, which reversed with appropriate therapy. Conclusion: High Dose Rate Brachytherapy offers a highly effective treatment of skin carcinomas. Surface applicators, used in conjunction with HDR brachytherapy equipment, make a uniform dose distribution and sharp dose gradient at the edge of the treatment field. Surface applicators are easy and safe to use, and they fit very accurately for each fraction. These applicators have the ability to become the standard treatment for skin carcinomas in the near future. No significant financial relationships to disclose.
Time Period Compared to Birth Cohort in Connecticut Incidence Rates for Twenty-Five Malignant Neoplasms&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN2"&gt;3&lt;/xref&gt;
Authors: G C Roush, M J Schymura, T R Holford, C White, J T Flannery
Journal: JNCI Journal of the National Cancer Institute (1985)

Out of necessity and convenience many reports on population-based rates for cancer are limited to analyses by time period of diagnosis, and just how often cohort effects are important in cancer data has not been fully explored. To address this question, Connecticut cancer incidence rates for the years 1940-79 were fitted to the model: Log (incidence rate) = constant + age effect + period effect + birth cohort effect + error term. Data for each cancer site and sex were categorized into 10-year intervals by time period and age group. Significance testing for the curvilinear effects (which are estimable functions) of age (A), period (P), and cohort (C) in the 44 data sets led to no clear choice of model for three data sets; an APC model for 20, an AP model for 7, and an AC model for 14. These choices were corroborated by the RA2 index. Limitations in the interpretation of the results were enumerated. Presentation of population-based cancer rates by implicitly assuming an AP model is valuable (e.g., for studying age distribution in different regions or for age-adjustment in examining international variation or time trends). However, the assumption of an AP model may often be incorrect, as was shown to be the case for most of these 44 data sets. The implications for monitoring trends and generating etiologic hypotheses were discussed in light of the results for cutaneous malignant melanoma and cancers of the cervix, breast, ovary, lung, and bladder.
The Philadelphia Chromosome and Chronic Myelogenous Leukemia
Authors: J. H. Tjio, Paul P. Carbone, Jacqueline Whang, Emil Frei
Journal: JNCI Journal of the National Cancer Institute (1966)

Sixty of 73 consecutive patients with clinical and laboratory features of chronic myelogenous leukemia had the Philadelphia (Ph1) chromosome abnormality, as revealed by bone marrow and peripheral blood studies of chromosome morphology. The 13 Ph1-negative patients differed from the larger Ph1-positive group by having lower white blood cell and platelet counts and by having a larger proportion of young children under the age of 7. However, the most significant difference was the finding that the Ph1-negative patients responded poorly to chemotherapy and had a median survival of 18 months as compared to 45 months for the Ph1-positive population (P < 0.01). The Ph1 chromosome was observed during all phases of the disease and was unaffected by treatment. In addition to the Ph1 chromosome, aneuploidy, manifested usually by hyperdiploid Ph1-positive cell lines, was present in 20 percent of the patients. In 2 patients, 2 Ph1 chromosomes were seen in the same cell. A single patient with marked aneuploidy had the only chromosome abnormality seen in the 13 Ph1-negative patients.
The gender gap in first authorship of research papers
Authors: Kathryn M Rexrode
Journal: BMJ (2016)

Parity of authorship should be a priority for journals, universities, and funding agencies

Women have been attending medical school in numbers equal to or greater than those of men since 1996 in the United Kingdom,1 and in nearly equal numbers in the United States since 2003.2 However, despite parity in medical school admissions, substantial gender differences in rank and leadership remain in academic medicine. The progress of women attaining first and senior authorship of original research publications, the currency of success for promotion in academic medicine, will directly translate into equity of academic advancement for women in the future.

In a linked paper (doi:10.1136/bmj.i847),3 Filardo and colleagues examined the prevalence of female first authorship among original research articles published over the past two decades (1994-2014) in six high impact general medical journals. This study is notable for its rigor, examining six issues a year for all selected journals throughout the 20 year study period and using online searches of authors to identify gender in those with ambiguous names. The authors report some good news—an …
Epizootic Neoplasms in the Clam Macoma balthica (L.) From Chesapeake Bay
Authors: Darryl J. Christensen, C. Austin Farley, Frederick G. Kern
Journal: JNCI Journal of the National Cancer Institute (1974)

Journal Article Epizootic Neoplasms in the Clam Macoma balthica (L.) From Chesapeake Bay Get access Darryl J. Christensen, Darryl J. Christensen Search for other works by this author on: Oxford Academic PubMed Google Scholar C. Austin Farley, C. Austin Farley Search for other works by this author on: Oxford Academic PubMed Google Scholar Frederick G. Kern Frederick G. Kern Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 52, Issue 6, June 1974, Pages 1739–1749, https://doi.org/10.1093/jnci/52.6.1739 Published: 01 June 1974 Article history Received: 10 September 1973 Accepted: 27 February 1974 Published: 01 June 1974
Abstract 1084: Myosin Light Chain Kinase Signaling Regulates Ectopic Atrial Activity
Authors: Paul Wolkowicz, Hernan E Grenett, Jian Huang, David D Ku, Ferdinand Urthaler
Journal: Circulation (2007)

Objective : Determine whether calmodulin (CaM) acts through novel signaling pathways to elicit left atrial ectopic activity. Methods : Rat left atria (n=6 –9 per group) were isolated and superfused at 30°C. Mechanical function was recorded using a Grass recorder. Left atrial proteins were analyzed using Western analysis. Findings : Our rat left atria are quiescent in the absence of external pacing. However, in the presence of 2-aminoethoxydiphenyl borate (20μM; 2APB), a novel sarcoplasmic reticulum (SR) calcium leak inducer, left atria contract spontaneously at 67±12 contractions (min) − 1 in the absence of pacing. Pre-treating left atria with two irreversible CaM inhibitors, phenoxybenzamine and fluphenazine chloroethane (90μM each), decreases spontaneous contraction frequency to 5±3 and 2±1 (min) − 1 , respectively, indicating CaM signaling is activated and required for this ectopic activity. Pre-treating left atria with 20μM KN62 did not decrease the frequency of 2APB-induced ectopic activity (72±8 contractions (min) − 1 ) indicating calmodulin-dependent protein kinase II (CAMKII) is not a downstream target here. In contrast, 20μM ML7, a specific inhibitor of myosin light chain kinase (MLCK), a second cardiac CaM-regulated kinase, decreases 2APB-induced spontaneous contractions to 7±3 min −1 . Western analysis shows left atria contain smooth muscle MLCK. This kinase preferentially phosphorylates non-muscle myosin light chain 2 (nmMLC2). Western analyses also show left atria contain nmMLC2 which is not phosphorylated in untreated muscles. However, nmMLC2 phosphorylation increases significantly in left atria exposed to 2APB. Conclusions : CaM and MLCK inhibitors prevent the ectopic atrial activity induced by 2APB. This suggests a unique SR calcium leak occurs under this condition which activates CaM signaling whose specific downstream target is MLCK, a major myocardial CaM-dependent kinase. MLCK signaling via its sole substrate, nmMLC2, is required for this novel ectopic atrial activity. Hyperphosphorylation of SR ryanodine receptors by CAMKII is known to induce an SR calcium leak that underlies triggered ectopic activity. Our data suggest multiple calcium leaks and CaM signaling pathways regulate the stability of intact atrial muscle.
Reverse transcriptase inhibitors reduce tumor growth in vivo and induce cell differentiation
Authors: M. Landriscina, M. Quirino, I. Sciamanna, C. Pittoggi, E. D'Argento, G. Schinzari, G. Di Leonardo, A. Cassano, C. Spadafora, C. Barone
Journal: Journal of Clinical Oncology (2004)

3134 Background: Endogenous, nontelomeric reverse transcriptase (RT) is encoded by two classes of genomic repeated elements: retrotransposons and endogenous retroviruses. Expression of RT-coding genes is generally repressed in differentiated non pathological tissues, yet is active in the germ-line, embryonic tissue and tumor cells. We reported that nevirapine, a non-nucleosidic RT inhibitor, reduces cell growth and induces differentiation in murine and human cell lines. Furthermore, nevirapine treatment causes a reprogramming of gene expression in murine transformed cells: particularly significant changes occur in genes involved in cell cycle control, such as down-regulation of cyclin D1 and up-regulation of p16, (Mangiacasale, Oncogene 2003). Finally, RT inhibitors are currently used in the treatment of HIV patients and epidemiological studies suggested that these drugs induce a dramatic decrease in the incidence of HIV-related neoplasms. Results: We report that treatment with two RT inhibitors, nevirapine and efavirenz, effectively induces a reversible inhibition of cell growth in human prostate (PC3), colon (HT29), small-cell lung (H69) cancer cell lines as well as in human melanoma (A-375) and glioma (U343), in vitro. Neither drug displays significant cytotoxic effects, producing minimal induction of necrosis and apoptosis. The inhibition of cell growth correlates with the accumulation of cells in the G0/G1 phase of cell cycle, concomitant with decrease in S-phase cells. Moreover, treated cells acquire a differentiated phenotype. Tumor xenografts from human prostate, colon, melanoma and small-cell lung cancer cells in nude mice treated with efavirenz show a strong reversible inhibition of growth. Maximal inhibition of cancer growth is obtained with a dose of 20 mg/kg b.w., which is within the therapeutical dose range used to achieve RT inhibition in patients with retrovirus infections such as HIV. Conclusions: These findings suggest that endogenous RT may represent a novel target in human cancer therapy and support the proposal that efavirenz could be tested as a new safe drug in association with standard anti-cancer treatments in humans. No significant financial relationships to disclose.
Zika fever and congenital Zika syndrome: An unexpected emerging arboviral disease
Authors: Jasper F.W. Chan, Garnet K.Y. Choi, Cyril C.Y. Yip, Vincent C.C. Cheng, Kwok-Yung Yuen
Journal: Journal of Infection (2016)

Unlike its mosquito-borne relatives, such as dengue, West Nile, and Japanese encephalitis viruses, which can cause severe human diseases, Zika virus (ZIKV) has emerged from obscurity by its association with a suspected "congenital Zika syndrome", while causing asymptomatic or mild exanthematous febrile infections which are dengue- or rubella-like in infected individuals. Despite having been discovered in Uganda for almost 60 years, <20 human cases were reported before 2007. The massive epidemics in the Pacific islands associated with the ZIKV Asian lineage in 2007 and 2013 were followed by explosive outbreaks in Latin America in 2015. Although increased mosquito breeding associated with the El Niño effect superimposed on global warming is suspected, genetic changes in its RNA virus genome may have led to better adaptation to mosquitoes, other animal reservoirs, and human. We reviewed the epidemiology, clinical manifestation, virology, pathogenesis, laboratory diagnosis, management, and prevention of this emerging infection. Laboratory diagnosis can be confounded by cross-reactivity with other circulating flaviviruses. Besides mosquito bite and transplacental transmission, the risk of other potential routes of transmission by transfusion, transplantation, sexual activity, breastfeeding, respiratory droplet, and animal bite is discussed. Epidemic control requires adequate clearance of mosquito breeding grounds, personal protection against mosquito bite, and hopefully a safe and effective vaccine.
Efficacy of first-line tocilizumab therapy in early polymyalgia rheumatica: a prospective longitudinal study
Authors: Valérie Devauchelle-Pensec, Jean Marie Berthelot, Divi Cornec, Yves Renaudineau, Thierry Marhadour, Sandrine Jousse-Joulin, Solène Querellou, Florent Garrigues, Michel De Bandt, Maelenn Gouillou, Alain Saraux
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Glucocorticoids are the cornerstone treatment of polymyalgia rheumatica (PMR) but induce adverse events. <h3>Objectives</h3> To evaluate the efficacy and safety of first-line tocilizumab in PMR. <h3>Methods</h3> In a prospective open-label study (ClinicalTrials.gov: NCT01713842), 20 glucocorticoid-free patients fulfilling Chuang9s PMR criteria, with symptom onset within the last 12 months and a PMR activity score (PMR-AS) &gt;10, each received three tocilizumab infusions at 4-week intervals, without glucocorticoids, followed by oral prednisone from weeks 12 to 24 (0.15 mg/kg if PMR-AS ≤10 and 0.30 mg/kg otherwise). The primary end point was the proportion of patients with PMR-AS≤10 at week 12. <h3>Results</h3> Baseline median PMR-AS was 36.6 (IQR 30.4–43.8). At week 12, all patients had PMR-AS≤10 and received the low prednisone dosage. Median PMR-AS at weeks 12 and 24 was 4.5 (3.2–6.8) and 0.95 (IQR 0.4–2), respectively (p&lt;0.001 vs baseline for both time points). No patient required rescue treatment. Positron emission tomography-CT showed significant improvements. The most common adverse events were transient neutropenia (n=3) and leucopenia (n=5); in one patient, the second tocilizumab infusion was omitted due to leucopenia. <h3>Conclusions</h3> Tocilizumab monotherapy is effective in recent-onset PMR. Randomised controlled trials are warranted. <h3>Trial registration number</h3> NCT01713842.
Results of a Feasibility and Phase II Study on Bortezomib (BTZ) in Pediatric Multiply Relapsed or Refractory Acute Lymphoblastic Leukemia: Complete Hematological Responses with a Modestly Intensive Regimen Including BTZ
Authors: Gertjan Kaspers, Denise Niewerth, Satianand Ramnarain, Andishe Attarbaschi, André Baruchel, Evelina S De Bont, Franca Fagioli, Barbara De Moerloose, Karsten Nysom, Giuseppe Palumbo, Dirk Reinhardt, Pierre-Simon Rohrlich, Pauline Simon, Arend von Stackelberg, C. Michel Zwaan
Journal: Blood (2014)
Abstract 19907: Clinical Prediction Risk Scores Systematically Underestimate the Presence and Extent of Subclinical Atherosclerosis in Brazilian Women: The Brazilian Study of Longitudinal Health (ELSA-Brasil)
Authors: Marcio S Bittencourt, Alexandre C Pereira, Henrique L Staniak, Rodolfo Sharovsky, Luz Marina Gomez, Vytor Hugo Mendes, Ron Blankstein, Khurram Nasir, Isabela Bensenor, Paulo A Lotufo
Journal: Circulation (2014)

Introduction: Different scores were developed to predict cardiovascular events in different populations. Due to genetic, social and economical differences, their performances vary according to the population to which they are applied. While there is concern that some scores may underestimate risk in women, few data exist for the Brazilian population. Hypothesis: Clinical risk scores will underestimate the coronary artery calcium (CAC) in Brazilian women. Methods: In a substudy from the ELSA-Brasil, a multicenter prospective study that enrolled civil servants in Brazil, 4546 participants underwent a CAC score. We calculated the Framingham risk score, Reynolds score, ASSIGN, PROCAM and both the low and the high European SCORE. To test the ability of each score to predict CAC values, we used a zero inflated model, which accommodates better CAC distribution. This is a two part model; the discrete part evaluates the association of the predictor with the probability of a CAC=0, and the continuous part of the model evaluates the association of the score with the CAC value. Results: The population included 1868 (55%) women with a mean age of 48±8 years. The median CAC was 0 (range 0 - 5363). In figure 1 we present the association of each score with the CAC values stratified by gender. All score are significantly associated with the discrete part of the model (probability of a CAC=0) (p&gt;0.001). However, while all scores were associated with the continuous part of the model for men (p&lt;0.0001); only the Reynolds (p=0.035) and the high SCORE (p&lt;0.0001) were associated with the continuous part of the model in women, whereas the Framingham score (p=0.96), ASSIGN (p=0.33) and PROCAM (p=0.78) were not. Figure 1 shows the association of each score with the CAC results stratified by gender. Conclusions: In a large Brazilian cohort, all clinical risk scores were significantly associated with the presence of CAC in men, whereas only the SCORE and Reynolds were associated with CAC values in women.
Reduced Expression of SMAD4 Is Associated with Poor Survival in Colon Cancer
Authors: Pu Yan, Dirk Klingbiel, Zenia Saridaki, Paola Ceppa, Monica Curto, Thomas Alexander McKee, Arnaud Roth, Sabine Tejpar, Mauro Delorenzi, Fredrik T. Bosman, Roberto Fiocca
Journal: Clinical Cancer Research (2016)

SMAD4 loss is associated with the development of metastases and poor prognosis. We evaluated expression of SMAD4 protein and its association with tumor characteristics, including biomarkers and outcome in terms of relapse-free survival and overall survival.We used 1,564 stage II/III colon cancer samples from PETACC-3 to evaluate SMAD4 expression by immunohistochemistry. SMAD4 protein expression was validated by assessing mRNA expression using available expression array data. SMAD4 expression was also studied on 34 adenomas and 10 colon cancer liver metastases with their primaries. Loss of SMAD4 immunoreactivity was defined as focal or diffuse. Cases without SMAD4 loss were subdivided into those with strong and weak expression.SMAD4 protein expression was informative in 1,381/1,564 cases. SMAD4 loss was found in 293/1,381 (21%) cases. Of 1,088 cases without SMAD4 loss (79%), 530 showed weak and 558 strong expression. SMAD4 loss occurred also in adenomas, but less extensively than in carcinomas. Liver metastases followed mostly the expression pattern of the primary tumor. SMAD4 loss, including weak expression, identified patients with poor survival in stage II as well as III and in both treatment arms. SMAD4 loss was less frequent in tumors with microsatellite instability and more frequent in those with loss of heterozygosity of 18q.We conclude that clonal loss of SMAD4 expression in adenomas, carcinomas, and liver metastases increases with disease progression. SMAD4 loss, and to a lesser extent weak expression, is strongly associated with poor survival regardless of stage. Clin Cancer Res; 22(12); 3037-47. ©2016 AACR.
Characteristics of a Cytotoxic Human Lymphocyte-Dependent Antibody&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 Wunderlich, E Rosenberg, J Connolly, J Parks
Journal: JNCI Journal of the National Cancer Institute (1975)

Lymphocyte-dependent antobody (LDA) from the blood of a patient with choriocarcinoma was characterized in an allogeneic in vitro system. The antibody reacted with specific traget cells, including cells from the patient's husband. Antibody-coated traget cells were damaged by normal lymphocytes from man and other species. Neither cytotoxic, complement-dependent antibody nor sensitized cytotoxic lymphocytes were found in the patient. LDA activity was associated with IgG gamma-globulin by G-200 Sephadex filtration, electrophoretic mobility, and reactivity with anti-IgG, but there was no activity associated with IgM immunoglobulin. Sera from 14 of 16 normal donors lacked detectable LDA activity, and only low levels were found in sera from the other two donors.