tbuckley/cabot-search huggingface dataset:
Anal intraepithelial neoplasia progression to squamous cell carcinoma.
Authors: Bhavna Gami, Paul Ziprin, Robert D Goldin, Michael Osborn, Linda Greene, John Walsh
Journal: Journal of Clinical Oncology (2013)

353 Background: In the U.K., the annual incidence of anal cancer is up to 1.5 per 100,000 per year. Anal intra-epithelial neoplasia (AIN) is believed to be a precursor to squamous cell carcinoma whose incidence is still undetermined. This cell transformation has been associated with human papillomavirus (HPV) infections, in particular HPV 16 and 18. Our aim was to determine the frequency of progression to squamous cell carcinoma (SCC) of the anus in patients with known AIN. Methods: Study subjects with diagnosis of AIN from January 1 st 1997 to January 1 st 2009 were identified from a prospective database in a single hospital trust. The incidence of a subsequent diagnosis of anal SCC was determined from the local pathology and anal cancer database and cross referenced with the regional cancer database, Thames Cancer Registry. Results: We identified 397 patients (303 males) diagnosed with AIN in the database and HPV infection was identified in n= 395 patients. 15 (4%) patients were diagnosed with anal SCC a median of 5 months, Interquartile range 27 (2- 29 months) after their initial diagnosis. The distribution of AIN 1, 2 and 3 at presentation was 2, 1 and 12 respectively. Of interest, number of patients developed other HPV related cancers during the study period, such as vulva (n=8), cervical (n=3) and penile cancers (n=1). Conclusions: The incidence of anal cancer is higher in patients with known AIN compared to the general population. This justifies surveillance of these patients for anal and other HPV related intraepithelial neoplasia, however the nature of this, anoscopy or clinical examination alone, has yet to be determined.
A meta-analysis of neoadjuvant chemotherapy for resectable stage 1–3A non-small cell lung cancer
Authors: Y. Huang, Y. Wu, X. Yang
Journal: Journal of Clinical Oncology (2005)

7265 Background: Adjuvant chemotherapy has showed survival benefit for patients with early stage NSCLC in last two years. There were some clinical trials in evaluating the role of neoadjuvant chemotherapy for resectable stage 1–3A non-small cell lung cancer. The evidence was not enough to recommend as guideline in practice. Methods: Clinical control trials published between 1994 and 2004 on neoadjuvant chemotherapy for resectable NSCLC were included. Statistical analysis was performed using SPSS, including tests for homogeneity of studies and publication bias. Trials were analyzed by odds ratio (OR). Revman4.1 software was applied to process data. Results: Eight trials were included in meta analysis. A total of 1965 patients were included in the analysis (1001 cases in the neoadjuvant group and 964 in the surgery group). There was statistical significant difference in survival between the two groups. The odds ratio (OR) was 0.68 with 95% CI 0.56 to 0.83, p=0.0002). After further analysis, there was not statistical significant difference in survival in the higher quality trials (review scores >8). The OR was 0.80 with 95% CI 0.58to 1.09, p=0.15). There was statistical significant difference in survival in the lower quality trials (review scores <8). The OR was 0.62 with 95% CI 0.48 to 0.62, p=0.0002). Conclusions: It is not certain that neoadjuvant chemotherapy improved survival in patients with resectable stage 1–3A NSCLC. It is needed more RCT to answer this question. No significant financial relationships to disclose.
A phase I trial of VB-111, a tissue- and condition-specific dual action vascular disruptive and antiangiogenic agent, for treatment of patients with advanced metastatic cancer.
Authors: A. J. Brenner, Y. Cohen, F. J. Giles, E. C. Borden, E. Breitbart, L. Bangio, N. Sher, P. L. Triozzi
Journal: Journal of Clinical Oncology (2011)

3038 Background: VB-111 is a tissue and condition specific vascular disrupting and anti-angiogenic agent based on a novel Vascular Targeting System (VTS) which contains the modified angiogenic specific pre-proendothelin promoter, and a FAS/TNF receptor chimeric transgene. Preclinical studies have shown that VB-111 has significant antitumor activity. We report the results of a phase I single-dose escalation study of VB-111 in patients with advanced metastatic solid tumors. Methods: Eligible patients had advanced solid tumors, with no existing curative therapy, and adequate organ function and performance status. VB-111 was administered as a single intravenous infusion at escalating doses ranging from 1X1010 to 1X1013 viral particles in seven successive cohorts. Primary and secondary endpoints were safety and efficacy at 56 days post dosing, respectively. Results: Thirty three patients enrolled in two cancer centers. VB-111 was well tolerated; most patients in Cohorts 5 to 7 developed self-limited fever and chills. Neutralizing antibodies to Ad-5 at baseline were elevated in over half of the patients. Ad-5 DNA blood levels gradually declined within 1 to 56 days post dosing; some patients had up to 103 copies/ µg genomic DNA at day 56. As expected from the specificity of VB-111, no expression of the Fas chimeric transgene in the blood was found. However, in a patient with esophageal cancer, transgene expression was detected in the aspirate from a subcutaneous metastasis 4 and 28 days after treatment. Three out of 14 (21%) evaluable patients in cohorts 1 to 5 vs. 9 out of 18 evaluable patients in cohorts 6 and 7 (50%) had stable disease at day 56. One patient with papillary thyroid carcinoma had PR at 6 months, which persisted for 18 months. Three patients, one with neuroendocrine and two with thyroid carcinoma had a significant decline in tumor-markers. Conclusions: VB-111 was found to be safe, well tolerated and showed some evidence for anti-tumor effect in patients with advanced metastatic cancer at a single administration of up to 1X1013 VPs. Repeat dose administration as well as evaluation in specific tumors will be explored in future studies.
Salvicine inactivats beta-1 integrin and inhibits MDA-MB-435 cell adhesion to fibronectin via reactive oxygen species signaling.
Authors: Jin Zhou, Yi Chen, Jin-yu Lang, Jin-sheng Zhang, Jian Ding
Journal: Cancer Research (2007)

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

3038 

Salvicine (SAL) is a novel diterpenoid quinone compound synthesized by the structural modification of a natural product isolated from a Chinese medicinal plant, Salvia prionitis lance . It possesses a broad spectrum of antitumor and antimetastatic activities in vitro and in vivo . It shows well-tolerability in Phase I study and is now under Phase II clinical trials in China. Our previous study indicated that its antimetastatic effect is closely related to Rho pathway. In this study, we revealed that salvicine inhibited the integrin-mediated human breast cancer cells MDA-MB-435 cell-ECM adhesion and spreading via reactive oxygen species (ROS) generation, which also contributed to its antimetastatic effect.

SAL inhibited MDA-MB-435 cells adhesion to fibronectin and collagen in a dose-dependent manner. When incubated with 8 μM salvicine for 1h, the adhesion to fibronectin and collagen was only 12.7% and 14.3% compared to control. But it had no effect on the nonspecific adhesion to poly-L-lysine. The formation of focal adhesions and actin stress fibers were also disrupted by SAL. Flow cytometry assay declared that the expression level of β1 integrin didn’t change after exposure with 8 μM SAL for 1h, but its affinity and clustering were obviously decreased. Furthermore, we investigated the mechanism that how SAL blocked integrins function, and revealed that ROS acted as an important role. SAL treatment quickly stimulated ROS generation in 435 cells, which started at 5min and peaked at 60min. N-acetyl-cysteine (NAC), a widely used ROS scavenger, not only abrogated the SAL-induced ROS enhancement, but also reversed β1 integrin affinity, restored cell adhesion and spreading. The formation of focal adhesions and actin stress fibers, which disrupted by SAL were also protected by NAC. Simultaneously, hydrogen peroxide exhibited the similar results, it also inhibited cell adhesion and was reversed by NAC. These data gave the direct evidence to prove that ROS resulted in β1 integrin inactivation, which maybe play a vital role in salvicine-induced cell-ECM attachment inhibition. Moreover, SAL activated ERK, p38 MAPK and AKT in a dose- and time-dependent manner. Pretreatment with U0126 or SB203580, the inhibitor of ERK or p38 MAPK respectively, partly reversed the cell adhesion and β1 function, whereas PI3K inhibitor Wortmannin couldn’t do. So ERK and p38 MAPK might be ROS effectors, which were responsible for the inhibition of integrin function induced by salvicine.

In summary, our data discloses a novel role of ROS in regulation integrin affinity and cell adhesion through the mode of ROS-MAPK-β1 integrin. And to our knowledge, this is the first time to reveal that p38 MAPK may also exert inhibitory role in integrin activation.
Deficiency of 2,3-Dimethoxy-5-Methyl-6-Decaprenyl-1,4-Benzoquinone (Mitoquinone) and Hyperlactic Acidosis in Human Immunodeficiency Virus (HIV) Patients with Head and Neck Squamous Cell Carcinoma (HNSCC) Treated with Nucleoside Reverse Transcriptase Inhibitor (NRTI)-Based HAART and Chemoradiation.
Authors: Eugene McPherson, E. Mejia, E. Hazel, P. Tassy
Journal: Blood (2005)
Autologous Stem Cell Transplantation (ASCT) for Enteropathy-Associated T-Cell Lymphoma (EATCL): A Retrospective Study of the European Group for Blood and Marrow Transplantation (EBMT)
Authors: Esa Jantunen, Ariane Boumendil, Alessandro Rambaldi, Marc Schapira, Jian Jian Luan, Martin Gramatzki, Stig Lenhoff, Gunnar J. Oberg, Peter Dreger, Anna Sureda
Journal: Blood (2011)
Outcomes of patients (pts) with BRAF mutated (BRAF MT) Colorectal Cancer (CRC): The Royal Marsden Experience.
Authors: Hamzeh Kayhanian, Emily Goode, Joo Ern Ang, David Gonzalez de Castro, Francesco Sclafani, Ann Petruckevitch, Sheela Rao, David J. Watkins, Marco Gerlinger, David Cunningham, Ian Chau, Naureen Starling
Journal: Journal of Clinical Oncology (2016)

644 Background: BRAF MT metastatic CRC (mCRC) is associated with a poor prognosis. For the first time, we report outcomes for BRAF MT mCRC at a single tertiary centre, compared to a matched control group, since introduction of routine somatic BRAF and RAS mutation testing. Methods: Pts with BRAF MT mCRC (diagnosed Oct 2010-Nov 2014) were compared to a matched group of BRAF wildtype (WT) pts treated in same time period who were randomly selected after matching for age, sex and stage. Demographic, tumour characteristic and treatment data were collected. Overall (OS) and progression-free survival (PFS) were calculated using the Kaplan-Meier method and comparisons made using χ² test or Cox regression. Results: Of 503 pts tested, 59 (11.7%) had BRAF MT tumours (16 early stage, 16 recurrent and 27 de novo metastatic). Median age (years) at diagnosis was 68 (27-85) compared with 70 (29-85) for BRAF WT pts (p = 0.995). Median OS for pts with mCRC was 18.2 months (m) for BRAF MT and 41.1m for BRAF WT pts (HR 2.73 P &lt; 0.01). For BRAF MT and BRAF WT pts with mCRC, median PFS on first-line treatment (1L) was 8.1m (n = 37) and 9.2m (n = 81) respectively (HR = 1.10 [P = 0.69]), PFS on 2L was 5.1m (n = 21) and 9.0m (n = 49) respectively (HR = 1.84 [P = 0.03]) while PFS on 3L was 1.7m (n = 10) and 6.6m (n = 20) respectively (HR = 2.75 [P = 0.02]). Fluoropyrimidine based doublet regimens were used in 94.6%, 85.7% and 20% of BRAF MT pts in 1L, 2L and 3L respectively compared with 87.2%, 92.5% and 52.4% in BRAF WT pts. Pts with localised disease had a recurrence rate of 50% (16/32) for pts with BRAF MT compared with 52.4% (33/63) for BRAF WT pts (p = 0.83). Conclusions: In this case-control study, poor OS of pts with BRAF MT mCRC is associated with reduced clinical benefit beyond 1L. Sequential doublet chemotherapy remains a reasonable option in these pts. The role of BRAF mutation in predicting recurrence of early CRC warrants further study. [Table: see text]
A predictive model to identify cancer patients at risk for in-hospital mortality based on admission criteria.
Authors: K. Ramchandran, J. Shega, M. Schumacher, A. Rademaker, b. B. Weitner, E. Szmuilowicz, S. A. Weitzman
Journal: Journal of Clinical Oncology (2011)

6045 Background: To develop a predictive model to identify cancer patients at risk for in-hospital mortality based on admission criteria. Methods: A retrospective review of all patients admitted to the hematology-oncology floors from 08/01/08 to 07/31/09 was done. Data was obtained on day 1 of patient admission and included basic demographic information such as age, gender, admission type, as well as basic vital signs and laboratory data (one entry within 12 hours of admission). Survival data was confirmed with the social security index. Results: Our analysis was based on 3188 adult cancer patients who were admitted during the specified time period. The overall observed hospital mortality was 11%. Significant variables on our multivariate analysis included age (p=0.0001), assistance with a activities of daily living (p=0.0235), admission type (elective versus emergency) (p=0.0003), oxygen use (p<0.0001), vital sign abnormalities (pulse oximetry (p=.0372), temperature (p <.0001), heart rate (p=.0002) and bilirubin (p<0.0001). Based on the data from our multivariate analysis we developed the following model: Trigger Score = 19.4185 + 0.98*(admit type) + 0.6081*(ADL) + 0.0276*(admit age) – 0.2124*(temperature) + 0.019*(heart rate) – 0.0468*(pulse ox) – 0.00968 (systolic bp) + 0.9283*(O2 on admission). Higher values indicated greater risk of expiring. The median (range) of the scores was -2.91 (-5.47 to 3.85) for patients who survived and -1.57 (-4.28 to 1.40) for patients who expired. The C statistic was .790 and the Hosmer-Lemeshow goodness of fit test had a p value of .73. Conclusions: This study shows shows that a simple equation based on basic admission data can identify a subgroup of cancer patients at high risk for death during that hospitalization. Establishment of goals of care/ advance care planning for these patients is advisable. Prospective independent validation in different medical settings is warranted.
The Canadian partnership for quality radiotherapy: A model for radiation treatment quality and safety.
Authors: Jeffrey Quoc Cao, Jean-Pierre Bissonnette, Michael Donald Brundage, Peter Dunscombe, John French, Caitlin Gillan, Margaret Keresteci, Michael Milosevic, Matthew Parliament, Jason Schella
Journal: Journal of Clinical Oncology (2012)

266 Background: Innovative, overarching national, and international strategies for the assurance of safe and high quality radiation treatment (RT) are needed, given the rate of technologic innovation and shifts in traditional roles associated with RT planning and delivery. Methods: The Canadian Partnership for Quality Radiotherapy (CPQR) was created as an interprofessional alliance of the Canadian Association of Radiation Oncology (CARO), Canadian Organization of Medical Physicists (COMP), Canadian Association of Medical Radiation Technologists (CAMRT) and Canadian Partnership Against Cancer (CPAC), aimed at developing and promoting coordinated national strategies for high quality and safe RT. Results: A steering committee of national leaders from each profession and content experts in RT quality and safety was created, with financial and strategic backing provided by the federal government through CPAC. The vision and strategy were communicated broadly to the RT treatment community and to other stakeholders provincially, nationally, and internationally. ‘Quality Assurance Guidance for Canadian Radiation Treatment Programs’ was published online in April 2011 and empowered programs across the country to evaluate their internal procedures against these indicators. This document was downloaded over 875 times in the first 6 months, a measure of the demand and broad uptake in Canada and internationally. This early success has fostered other foci of activity, including engagement by the Canadian medical physics community around synthesis of detailed quality control guidelines for equipment, a dialogue about national incident reporting, and support from international partners in relation to collaborative programs. The goal is to incorporate RT quality and safety indicators into national accreditation programs for cancer care to assure long-term sustainability. Conclusions: CPQR has established a model for quality and safety that is fostering the evolution of a new national quality culture. This model is applicable to other jurisdictions, recognizing that a coordinated international approach to setting guidelines and standards will ultimately lead to higher quality and safer RT on a global scale.
Coronary heart disease 55+ years after lower-dose thoracic irradiation: Preliminary results.
Authors: M. J. Adams, S. G. Fisher, S. E. Lipshultz, R. E. Shore, L. S. Constine, M. Stovall, A. Dozier, R. G. Schwartz, R. C. Block, T. A. Pearson
Journal: Journal of Clinical Oncology (2010)

e19554 Background: Thoracic radiotherapy (RT) for treatment of childhood cancer is reported to increase myocardial infarction (MI) incidence. Much of this evidence is based on studies of Hodgkin lymphoma survivors treated with older RT techniques that exposed the heart to the full dose of therapeutic irradiation. Our goal was to evaluate the impact of more modern cardiac shielding techniques of RT on the magnitude and timing of CV risk by studying a cohort exposed to similar levels of cardiac irradiation years ago. Methods: A population-based, longitudinal cohort of subjects exposed to irradiation for an enlarged thymus during infancy from 1926 to 1957 and of their non-irradiated siblings was reestablished between 2004 and 2008. Coronary heart disease (CHD) events were assessed using a mailed survey and checking cause of death in the National Death Index. We used Poisson regression methods to compare incidence rates by irradiation status and cardiac radiation dose. Results: Subject's median age and length of follow-up was 57.5 years (range 41.2-88.8 yrs) among both irradiated and non-irradiated siblings. Eighty-four irradiated individuals (mean cardiac dose 1.45 Gy; range 0.17-20.20 Gy) had a MI during 124,631 person-years of follow-up compared to 131 non-irradiated siblings with a MI during 210,604 person-years. This resulted in a rate ratio of 0.99 (95%CI: 0.75-1.30) after adjustment for attained age and gender. The adjusted rate ratio for all CHD events (MI, bypass surgery and angioplasty) was 1.09 (95%CI: 0.88-1.35). No significant dose-effect association was observed for incidence of MI or all CHD events. Conclusions: These preliminary results suggest reduction of cardiac radiation doses to the levels in our cohort (mean dose of 1.45 Gy) without increasing other cardiotoxic therapies may eliminate or at least delay into the 7th decade of life increased MI risk. Further analysis is required, including adjustment for other traditional CHD risk factors. No significant financial relationships to disclose.
Bacterial and Virus Diseases: Antisera, Toxoids, Vaccines and Tuberculins in Prophylaxis and Treatment
Authors: Ment By, H Parish
Journal: JAMA (1952)

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Phase II trial of docetaxel and cisplatin in 5-FU/cisplatin pretreated refractory esophageal cancer
Authors: H. Shim, W. Bae, J. Hwang, S. Cho, T. Nam, I. Chung
Journal: Journal of Clinical Oncology (2008)

15626 Background: This study was performed to determine the feasibility and safety of the salvage chemotherapy with docetaxel and cisplatin in 5-FU/cisplatin pretreated refractory esophageal cancer. Methods: Patients with histologically confirmed esophageal cancer pretreated with 5-FU and cisplatin ± radiotherapy, ECOG PS ≤ 2, at least one measurable lesion and adequate organ functions were eligible. Docetaxel (70 mg/m2) and cisplatin (75 mg/m2) were given as an 1-h intravenous infusion on day 1, repeated every 3 weeks. Results: Twenty-three patients were enrolled and twenty patients were evaluable. Their median age was 65 years (male/female =23/0); ECOG performance status 0/1/2/3=0/10/12/1; dysphagia score 0/1/2/3/4=0/4/13/5/1). The median and total number of cycles delivered was 4 (range, 1–9 cycles) and 81, respectively. Partial response was shown in four patients (20%; 95% CI, 5.7- 43.7%), stable disease was shown in eight (40%; 95% CI, 16.1–63.9%) and eight patients had progressive disease (40%; 95% CI, 19.1–63.9%). Therefore, ORR was seen in 20% and disease control rate was 60%. Nine patients (45%) improved their dysphagia by more than one grade based on DeMeester symptom scores. The median time to progression was 16.9 ± 7.1 (95% CI, 3.1–30.7) weeks, and the median overall survival was 7.1 ± 2.5 (95% CI, 2.2–12.0) months. The main hematological toxicities were neutropenia and leucopenia. Greater than grade 3 neutropenia and leucopenia were developed in 8 (34.8%) and 7 patients (30.4%), respectively. There was no febrile neutropenia. Greater than grade 3 nonhematologic toxicities were asthenia ( 2 patients) and nausea (1 patient). Conclusions: The combination chemotherapy with docetaxel and cisplatin is feasible and safe in 5-FU and cisplatin pretreated esophageal cancer. No significant financial relationships to disclose.
A tribute to Professor Shu Dong Xiao (1931–2016)
Authors: Jing Yuan Fang
Journal: Gut (2017)

institute of digestive disease in China, the Shanghai Institute of Digestive Disease, where he established endoscopy as the main focus of diagnosing and treating GI diseases.Professor Xiao was a pioneer in several fields of GI disease including GI tumours and their precancerous lesions, and most notably Helicobacter pylori infection and its related diseases.
Mutations of the TP53 Gene Play an Important Role in the Pathogenesis of Acute Myeloid Leukemia with Complex Aberrant Karyotype.
Authors: Claudia Schoch, Frank Dicker, Alexander Kohlmann, Sonja Rauhut, Wolfgang Hiddemann, Susanne Schnittger, Wolfgang Kern, Torsten Haferlach
Journal: Blood (2004)