tbuckley/cabot-search huggingface dataset:
Characterization of prostate cancer information available on smartphones.
Authors: Danny Landau, Julio Hajdenberg
Journal: Journal of Clinical Oncology (2012)

e15102 Background: When seeking information regarding prostate cancer, patients are often turning to Smartphones. We decided to look at the “top applications” (apps) on the iTunes store to determine the quality of information provided. Methods: In November 2011 on an iPhone the search “Prostate Cancer” was entered. The first page of apps was downloaded and studied (18 in total). They were categorized into apps written at a provider level and apps written for a patient level. The patient apps were then broken into patient support, cancer detection, disease monitoring, advertisements, and patient knowledge. The quality of paid apps was also looked at. Results: Of the 18 apps, two were unrelated to prostate cancer. Of the remaining 16, six were provider apps. Of these six, two were apps for major oncology journals, three were staging guidelines, and one was for a general oncology reference guide. Of the patient directed apps, patient information (general prostate cancer information) apps were four, two were apps to provide support, one was devoted to disease detection which included discussions on prostate specific antigen testing, one for monitoring disease, and one was an advertisement for a radiation technique. One app, once downloaded, required additional payment and personal information prior to giving the promised information. This application was not pursued. Paid apps accounted for eight apps. Two were geared toward providers. Both were prostate cancer staging guidelines. The patient directed paid apps included two apps which provided medically appropriate, level one evidence based information. Two provided information that wasn’t based on accepted medical therapy, including diet advice to prevent cancer and “alternative therapies” including reflexology, roots, and hypnosis as therapies. All free apps that were devoted to prostate cancer were based on level one evidence. Two additional paid apps were unrelated to prostate cancer. Conclusions: The majority of applications available over the iTunes store provide solid evidence and may be a valuable resource to patients and providers. Only the patient directed paid apps provided information that can be deemed questionable.
Circulating melanoma cells isolated from clinical blood samples and characterized by full-length mRNA sequencing at single-cell level.
Authors: Yu-Chieh Wang, Daniel Ramskold, Shujun Luo, Robin Li, Qiaolin Deng, Gregory A. Daniels, Irina Khrebtukova, Jeanne F. Loring, Louise C. Laurent, Gary P. Schroth, Rickard Sandberg
Journal: Journal of Clinical Oncology (2012)

10539 Background: Melanoma is the most aggressive type of skin cancer. Late-stage melanoma is highly metastatic and currently lacks effective treatment. This discouraging clinical observation highlights the need for a better understanding of the molecular mechanisms underlying melanoma initiation and progression and for developing new therapeutic approaches based on novel targets. Although genome-wide transcriptome analyses have been frequently used to study molecular alterations in clinical samples, it has been technically challenging to obtain the transcriptomic profiles at single-cell level. Methods: Using antibody-mediated magnetic activated cell separation (MACS), we isolated and individualized putative circulating melanoma cells (CMCs) from the blood samples of the melanoma patients at advance stages. The transcriptomic analysis based on a novel and robust mRNA-Seq protocol (Smart-Seq) was established and applied to the putative CMCs for single-cell profiling. Results: We have discovered distinct gene expression patterns, including new putative markers for CMCs. Meanwhile, the gene expression profiles derived of the CMC candidates isolated from the patient’s blood samples are closely-related to the expression profiles of other cells originated from human melanocytes, including normal melanocytes in primary culture and melanoma cell lines. Compared with existing methods, Smart-Seq has improved read coverage across transcripts, which provides advantage for better analyzing transcript isoforms and SNPs. Conclusions: Our results suggest that the techniques developed in this research for cell isolation and transcriptomic analyses can potentially be used for addressing many biological and clinical questions requiring genomewide transcriptome profiling in rare cells.
Quantitative identification of mutant alleles derived from lung cancer in plasma cell-free DNA via anomaly detection using deep sequencing data.
Authors: Junji Uchida, Yoji Kukita, Kazuya Taniguchi, Shigeyuki Oba, Kazumi Nishino, Toru Kumagai, Takako Okuyama, Toshie Niki, Fumio Imamura, Kikuya Kato
Journal: Journal of Clinical Oncology (2013)

e19153 Background: Selection of lung cancer patients to be treated with EGFR-TKI (gefitinib and erlotinib) is currently based on the presence of activating mutations in the EGFR kinase domain. The diagnosis of the mutations is based on biopsy samples; the procedure is invasive, and often difficult to perform. A non-invasive diagnostic procedure is desirable. Methods: We established a non-invasive diagnostic system to detect somatic mutations including three activating mutations (exon 19 deletion, L858R, L861Q) and one resistant mutation (T790M) with single-pass deep sequencing of EGFR gene fragments amplified from patients’ plasma DNA using Ion Torrent PGM. In principle, substitutions or deletions significantly higher (p=0.00002) than the error rates determined with the normal samples were judged as mutations. Read errors of the system were determined with deep sequencing (&gt;100,000 reads) of EGFR fragments. The detection limits were less than 0.01% for the exon 19 deletion and L858R, 0.01% for L861Q, and 0.05% for T790M. Results: We examined 155 samples, mostly plasma cell-free DNA, with mutation data of primary lesions. Exon 19 deletion, L858R, and L861Q were detected in 44 out of 72 samples (61.1%), 32 out of 56 (57.1%), and four out six, respectively. T790M was found in 26 samples, five of which did not accompany activating mutations. Considerable numbers of samples were collected from the same patients at different time points in the disease course. A temporal analysis revealed rapid disappearance of mutations by the EGFR-TKI therapy before radiological changes. Conclusions: Deep sequencing of amplified EGFR fragments from plasma DNA could detect mutations in lung cancer tissues. Results of the temporal analysis suggested potential applications for disease management and for therapeutic decision making to select EGFR-TKI. Clinical trial information: UMIN000006762.
Organ-specific inhibition of metastatic colon carcinoma by CXCR3 antagonism
Authors: B. S. Karimdjee, Miss B. Cambien, Mrs P. F. Richard, J. Bereder, Mr J. Scoazec, Mr D. Birnbaum, Mr N. Mounier, Mrs H. A. Schmid, Mrs A. A. Schmid
Journal: Journal of Clinical Oncology (2009)

e14619 Background: Liver and lung metastases are the predominant cause of colorectal cancer (CRC) related mortality. Recent research has indicated that CXCR3/chemokines interactions that orchestrate hematopoetic cell movement are implicated in the metastatic process of malignant tumors, including that of CRC cells to lymph nodes. To date, however, the contribution of CXCR3 to liver and lung metastasis in CRC has not been addressed. Methods: To determine whether CXCR3 receptors regulate malignancy-related properties of CRC cells, we have used CXCR3-expressing CRC cell lines of human (HT29 cells) and murine (C26 cells) origins that enable the development of liver and lung metastases when injected into immunodeficient and immunocompetent mice, respectively, and assessed the effect of CXCR3 blockade using AMG487, a small molecular weight antagonist. Results: In vitro, activation of CXCR3 on human and mouse CRC cells by its cognate ligands induced migratory and growth responses, both activities being abrogated by AMG487. In vivo, systemic CXCR3 antagonism by preventive or curative treatments with AMG487 markedly inhibited metastasis of human and mouse CRC cells to the lung without affecting that to the liver. Also, we measured increased levels of CXCR3 and ligands expression within lung nodules compared to liver tumors. Conclusions: Altogether, our findings indicate that CXCR3 is a key mediator for lung metastasis of colon carcinoma and identify CXCR3-blocking approaches as promising strategies against established lung metastases. No significant financial relationships to disclose.
Screening for Pancreatic Cancer
Authors: Jill Jin
Journal: JAMA (2019)

Nora B. Henrikson, PhD, MPH; Erin J. Aiello Bowles, MPH; Paula R. Blasi, MPH; Caitlin C. Morrison, MPH; Matt Nguyen, MPH; Venu G. Pillarisetty, MD; Jennifer S. Lin, MD, MCR
Effect of multifocality and multicentricity on outcome in early breast cancer: A systematic review and meta-analysis.
Authors: Francisco Emilio Vera-Badillo, Marc Napoleone, Alberto Ocana, Arnoud J. Templeton, Bostjan Seruga, Mustafa Al-Mubarak, Hashem Yaseen Al Hashem, Ian Tannock, Eitan Amir
Journal: Journal of Clinical Oncology (2014)

546 Background: Women with multifocal or multicentric breast tumors (multifocality henceforth) have been reported to have greater probability of nodal metastasis and relapse and worse survival than women with unifocal tumors. However, these associations have been inconsistent and multifocality is not taken into account by staging guidelines and prognostic models. Methods: A systematic review of Medline and EMBASE (host: Ovid) from 1946 to July 2013 identified publications exploring the association between multifocality and overall survival (OS), disease-free survival (DFS), disease-specific survival (DSS) and loco-regional relapse (LRR). The hazard ratios (HR) for OS and DFS for multifocal compared to unifocal tumors were extracted from multivariable analyses and included in a meta-analysis. For studies not reporting multivariable analyses, odds ratios (OR) were estimated from Kaplan-Meier curves for all endpoints at 5 and 10 years. Results: Twenty-two studies comprising 67,557 women were included. Multifocality was reported in 9.5% of patients. Classical prognostic factors were well balanced between unifocal and multifocal populations. In multivariable analyses, multifocality was associated with significantly worse OS (HR=1.65, p=0.02), and a non-significant association with worse DFS (HR=1.96, p=0.07). Inter-study heterogeneity was significant (Cochran Q p<0.001 in both analyses). Similar results were observed for the odds of death or disease recurrence by 5 years (OR=1.39, p=0.02; OR=1.52, p=0.02, respectively). Additionally, multifocality was associated with worse DSS and a higher odds of LRR (OR=1.56, p=0.03; and OR=3.23, p=0.02, respectively). Similar estimates were observed at 10 years but statistical significance was only reached for DSS and LRR (OS: OR=1.40, p=0.07; DFS: OR=1.49, p=0.06; DSS: OR=1.69, p<0.001; LRR: OR=2.94, p=0.03). Conclusions: Multifocality appears to be associated with a worse prognosis. Substantial inter-study heterogeneity limits the precise determination of increased risk; however, the inclusion of multifocality as an independent prognostic factor appears warranted.
Cancer‐Specific Therapy by Artificial Modulation of Intracellular Calcium Concentration
Authors: Cheng Wang, Fangying Yu, Xuerong Liu, Shaoqing Chen, Rui Wu, Rui Zhao, Fuqiang Hu, Hong Yuan
Journal: Advanced Healthcare Materials (2019)

Calcium (Ca2+ ) hemeostasis is crucial for the normal function of cellular biochemistry. The abnormal frequency of Ca2+ signaling in cancer cells makes them more vulnerable to Ca2+ modulation than normal cells. Here in this study, a novel cancer-specific therapy by artificially triggering Ca2+ overload in cancer cells is proposed. The feasibility of this therapy is illustrated by successful coupling of selective extrusion (Ca2+ ) inhibition effect of Curcumin (Cur) and the effective Ca2+ generating capability of amorphous calcium carbonate (ACC) into a facilely prepared water responsive phospholipid (PL)-ACC hybrid platform (PL/ACC-Cur). The obtained results demonstrate that PL/ACC-Cur can specifically boost the intracellular Ca2+ concentration to cause Ca2+ overload and to trigger mitochondria-related apoptosis in MCF-7 cells while sparing normal hepatocyte (L02), which might be a promising approach for effective cancer therapy.
Third-line antiretroviral therapy in low-income and middle-income countries (ACTG A5288): a prospective strategy study
Authors: Beatriz Grinsztejn, Michael D Hughes, Justin Ritz, Robert Salata, Peter Mugyenyi, Evelyn Hogg, Linda Wieclaw, Robert Gross, Catherine Godfrey, Sandra W Cardoso, Aggrey Bukuru, Mumbi Makanga, Sharlaa Faesen, Vidya Mave, Beatrice Wangari Ndege, Sandy Nerette Fontain, Wadzanai Samaneka, Rode Secours, Marije van Schalkwyk, Rosie Mngqibisa, Lerato Mohapi, Javier Valencia, Patcharaphan Sugandhavesa, Esmelda Montalban, Anchalee Avihingsanon, Breno R Santos, Nagalingeswaran Kumarasamy, Cecilia Kanyama, Robert T Schooley, John W Mellors, Carole L Wallis, Ann C Collier, B Grinsztejn, PN Mugyenyi, A Collier, R Salata, C Godfrey, E Hogg, M Hughes, J Ritz, L Wieclaw, T Sise, JW Mellors, C Wallis, CV Fletcher, M Gandhi, R Gross, RT Schooley, R Walensky, M van Schalkwyk, S Faesen, R Mngqibisa, J Valencia, E Montalban, N Kumarasamy, C Kanyama, SW Cardoso, BR Santos, B Mansfield, H Mugerwa, BW Ndege, R Secours, W Samaneka, D Kadam, V Mave, M Makanga, SN Fontain, P Sugandhavesa, A Avihingsanon, L Nakibuuka, H Nassolo, P Anthony, V Kulkarni, M Nsubuga, J van Wyk, J Rooney, Y van Delft, R Leavitt, R Luk, A Benns, L Hovind, A Shahkolahi
Journal: The Lancet HIV (2019)
Biomedical journals not dead yet
Authors: S E Quinn, G S Kenyon
Journal: BMJ (1995)

Electronic publications are hard to access

EDITOR,--We are sure that the paper free electronic dissemination of scientific journals is further away than Tony Delamothe and Ronald E Laporte and colleagues envisage.1 2 Computer literacy is not widespread, even in the United States, and is not helped by the computer industry, which often seems to conspire to make the use of personal computers an ordeal. Manuals are often written without simple …
Multiscale reverse engineering of the human ocular surface
Authors: Jeongyun Seo, Woo Y. Byun, Farid Alisafaei, Andrei Georgescu, Yoon-Suk Yi, Mina Massaro-Giordano, Vivek B. Shenoy, Vivian Lee, Vatinee Y. Bunya, Dongeun Huh
Journal: Nature Medicine (2019)
H pylori-positive gastric diffuse large B-cell lymphomas are potentially curable by H pylori eradication therapy
Authors: S. H. Kuo, L. T. Chen, M. S. Wu, C. W. Lin, K. T. Kuo, H. P. Wang, P. N. Hsu, J. T. Lin, A. L. Cheng
Journal: Journal of Clinical Oncology (2007)

8093 Background: We have recently demonstrated that early-stage gastric diffuse large B-cell lymphomas (DLBCLs) with MALToma, as well as their MALToma counterparts, may respond to H pylori eradication therapy (HPET). The present study was conducted to evaluate the effect of HPET in stage IE gastric DLBCLs without MALToma. Methods: Seven patients (4 men and 3 women; age range, 35 to 83 years) with H pylori infection and stage IE gastric DLBCL without MALToma received HPET as first-line treatment from June 2002 through May 2006. Additional immunohistochemical reaction with anticytokeratin was performed to exclude lymphoepithelial lesions (minimal MALToma components) in DLBCL. All patients received intensive endoscopic follow-up examinations with biopsy to evaluate tumor response. Patients with significant improvement of gross lesions that accompanied regression of tumor cells were followed up without additional treatment. Patients without significant improvement were immediately referred to systemic chemotherapy. Tumors that resolved to Wotherspoon grade 2 or less after successful HPET were considered as complete histologic remission. Results: Successful HPET was achieved in all patients. There were 5 patients with complete histologic remission. The complete remission rate was 71.4% (95% confidence interval, 45.1% to 97.7%). The median duration between HPET and complete histologic remission was 2.6 months (range, 1.1 to 5.7 months). At a median follow-up of 24.2 months (range, 5.7 to 56.8 months), all patients with complete histologic remission after HPET were alive and free of lymphoma. Conclusions: A substantial portion of early-stage gastric DLBCLs without MALToma remain H pylori-dependent and can potentially be cured by HPET. No significant financial relationships to disclose.
The predictive value of pretreatment 18-FDG- PET CT in locally advanced nasopharyngeal cancer patients treated definitively with induction chemotherapy followed by concurrent chemoradiotherapy.
Authors: Hala AHMED EL Lathy, Gehan Khder, Yousry Rostom, Tamer Refaat
Journal: Journal of Clinical Oncology (2013)

e17013 Background: This study aimed to evaluate the role of pretreatment [18F] fluorodeoxyglucose positron emission tomography (18F-FDG-PET) as a predictor of disease-free survival (DFS), and overall survival (OS) in locally advanced nasopharyngeal carcinoma (LANC) patients treated definitively with docetaxel-based induction chemotherapy followed by concurrent chemoradiation (CRT). Methods: After obtaining the institutional review board approval, we conducted a retrospective analysis of LANC patients (T1,N1-3 and T2-T4,anyN disease) treated definitively between January 2007 and December 2011 with induction chemotherapy docetaxel , cisplatin, and 5- flurouracil (TPF) followed by CRT utilizing weekly cisplatin and had pretreatment 18F-FDG-PET. We examined the association between the pretreatment primary tumor maximum standardized uptake value (SUVmax) and the treatment outcomes. The disease-free survival (DFS), and overall survival (OS) were calculated by the Kaplan-Meier method, and the differences were evaluated on logrank test. The prognostic significance was assessed by univariate and multivariate analyses. Results: The study included 38 eligible LANC patients. The 4-year OS and PFS rates were 94.9% and 84.7%, respectively. The median OS and PFS intervals were not reached. On univariate analysis, the 4-years DFS was significantly higher in patients with pretreatment SUVmax ≤ 8 compared to &gt; 8 (92.3% vs 56%, P = 0.017). It was also significantly correlated to pretreatment T stage (P=0.001), N stage (P=0.011) and the treatment response (P &lt; 0.001) and treatment breaks (P&lt; 0.001). On a multivariate analysis, the SUVmax category was the only factor correlated with 4-year DFS (hazard ratio = 13.2, 95% C I 1.27-136.8, P= 0. 030) but not for OS (P = 0.068). Conclusions: This study shows that the pretreatment primary tumor SUVmax is a potential independent prognostic predictor of clinical outcomes in patients with LANC treated definitively with TPF induction chemotherapy followed by CRT. Further randomized controlled clinical III trials are needed to provide clear evidence of this benefit.
Outpatient chemotherapy with gemcitabine and oxaliplatin in advanced biliary tract cancer; a phase II study
Authors: J. Harder, B. Riecken, O. Kummer, C. Lohrmann, M. Geissler, F. Otto, O. Opitz, H. Henss
Journal: Journal of Clinical Oncology (2006)

14006 Background: Biliary tract cancer is a heterogeneous tumor entity with a poor prognosis if unresectable. There is a need for an effective, safe and patient friendly treatment. Methods: Patients with typical histology for cholangiocarcinoma, adequate haematological, renal and liver function, measurable tumor formation, life expectancy for more than 3 months, and written informed consent were treated with Gemcitabine 1000mg/m 2 (30 min infusion) day 1, 8, 15 and Oxaliplatin 100mg/m 2 (2 h infusion) day 1 and 15. Chemotherapy cycles were repeated every 28 days (GEMOX-3 protocol). The data were collected according to the Simon 2-step design for a single centre phase II study (α=0.05; β=0.2). Planned sample size 29. Primary endpoint was the response rate; secondary endpoints were time to progression, median survival and safety profile. Results: Thirty-one consecutive patients were enrolled between July 2002 and April 2005. The efficacy was as follows: partial response 8 pts (26%), stable disease 14 pts (45%). Thus, the disease control rate was 71%, while 9 pts (29%) had progressive disease. Median time to progression was 6.5 months. Median overall survival after start of treatment was 10.4 months, after initial diagnosis it was 15.6 months. National Cancer Institute Common Toxicity Criteria grade 3–4 toxicities were transient thrombocytopenia in 23% of patients, peripheral sensory neuropathy 19%, leukopenia 16% and anaemia 10%. Conclusion: The GEMOX-3 protocol is active and well tolerated in patients with advanced biliary tract cancer. It can be applied in an outpatient setting with three treatments per month only. The positive results of this and other phase II trials underscore the importance of a large controlled clinical trial to verify the data. No significant financial relationships to disclose.
Effect of sequential chemotherapy and gefitinib on survival outcome in advanced NSCLC with acquired gefitinib resistance.
Authors: Wang Huijuan, Zhang Mina, Zhang guo Wei, Zhu Hui, Wang Qiming, Li Peng, Yan Xiangtao, Li Shaomei, Ma Zhi Yong
Journal: Journal of Clinical Oncology (2013)

e19085 Background: As one of the epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), gefitinib has been proven to be highly effective for patients with advanced NSCLC. However, almost all patients who experienced remarkable improvement eventually develop acquired resistance. There are no approved therapies after disease progression on gefitinib. Subsequent therapeutic modalities are needed. Methods: From September 2007 to July 2012, 74 patients with pathologically confirmed advanced NSCLC who had had disease control with gefitinib more than 6 months were retrospectively reviewed. After acquired resistance to gefitinib, 38 (51%) patients received systemic chemotherapy and sequential gefitinib, 14 (20%) received local treatment and continued gefitinib, and 22 (29%) received best supportive care (BSC) only.Our objective was to assess the survival outcome of different subsequent therapy after acquired resistance to gefitinib. Results: In chemotherapy group, Patients achieved higher response rate and disease control rate, respectively 39% and 82%. The median overall survival (OS) and progression free survival (PFS) from the time of gefetinib resistance in the subsequent chemotherapy group (13.9 m and 5.2 m, respectively) were longer than the local therapy group (7.1 m and 3.1 m, respectively) and the BSC group (3.7 m and 1.1 m, respectively; P &lt; .01). Furthermore, we found that patients who accepted subsequent therapy and continued gefitinib at the same time got better PFS and OS. Local therapy and in combination with continuation of gefitinib treatment could prolong time from local progress to distant metastasis. Conclusions: Subsequent therapy, especially sequential chemotherapy and gefitinib could bring gefetinib resistance NSCLC better survival outcome. Local therapy could also be a reasonable choice for local progress or metastasis patients during gefitinib treatment.