tbuckley/cabot-search huggingface dataset:
PTU-213 Oncological outcomes following local excision with and without (chemo)-radiotherapy for anal margin squamous cell carcinoma
Authors: TF Bullen, G Nanayakkara, L Malcomson, MP Saunders, R Kochhar, B Chakrabarty, PE Fulford, MS Wilson, ST O’Dwyer, AG Renehan
Journal: Gut (2015)

<h3>Introduction</h3> The mainstay of treatment for anal squamous cell carcinoma (ASCC) is chemo-radiotherapy (CRT). Less than 5% of initial presentations are confined to the anal margin and amenable to local excision (LE) with or without post-operative (C)RT. However, treatment is poorly defined and outcome is understudied. <h3>Method</h3> PLATO is the next UK anal cancer trial; a three-part umbrella trial where the first stream (ACT 3) is a phase II study to assess the use of LE, for T1N0 anal margin tumours, combined with low-dose post-operative CRT (41.4Gy in 23 fractions) for close margins (≤ 1 mm), evaluated against a minimally tolerated loco-regional actuarial relapse rate of 10%. To inform this trial, we report the characteristics, treatment and outcomes of patients treated through a large anal cancer MDT (2004 to 2013), supplemented by a literature review. <h3>Results</h3> From 446 patients with new ASSC, there were 20 (4%) anal margin tumours treated by LE. Thirteen (65%) were T1; 7 (35%) were T2. All were N0 and M0. The lateral and deep margins were close (≤ 1 mm) in seven patients (35%). Five patients had additional therapy: 2 RT; 3 CRT. With a median follow-up of 38.6 months, there were no primary site recurrences; 3 patients developed nodal relapses (3-year loco-regional relapse = 11%). Three patients died attributed to their disease – the 3-year disease-free survival rate was 89%. The literature search identified six studies – there was a near total paucity of data on tumour characteristics, excision margin status, and the impact of these on subsequent treatment or outcome. <h3>Conclusion</h3> There is a need for a contemporaneous prospective study of this sub-population of patients with anal cancer, through centralisation of patients to anal cancer MDTs with pro-active identification and recruitment of these patients for the ACT3 trial. <h3>Disclosure of interest</h3> None Declared.
Abstract 1382: Use of polarized light spectroscopy (CD) to study STAT3 folding and STAT3:ligand interactions
Authors: Khondaker M. Rahman, Jonathan Palmer, Samantha Essex, Edwin Nkansah, Giovanna Zinzalla, Andrew F. Wilderspin, Tam T.T Bui, Alex F. Drake, David E. Thurston
Journal: Cancer Research (2011)

Abstract STAT3 is a homodimeric transcription factor that is over-expressed in variety of solid tumours. It is known to trigger transcription of a range of genes associated with tumour growth and metastasis. In order to use the STAT3/STAT3 dimer for drug discovery, the factors affecting dimerisation of the monomeric protein and the interaction with ligands must be understood. In this study, we have demonstrated that Circular Dichroism (CD) can be used as a tool to study these processes. We have found that formation of the dimeric STAT3/STAT3 complex results in an induced CD signal which is absent in monomeric protein. Thus, CD can be used to optimize conditions for the production and storage of un-phosphorylated (un-P-) and phosphorylated (P-) STAT3. A similar induced signal was observed when a small molecule (or peptide ligand) interacted with either un-P- or P-STAT3 due to chiral perturbation of the protein structure or electron rearrangements. Crucially, the intensity of the induced CD signal was found to depend on the strength and geometry of the interaction of the binding partner. CD was also used to determine the secondary structure of un-P- and P-STAT3. HIS- and FLAG-tagged STAT3 were examined using the far-UV spectral region (190-250 nm), and the regular folded environment of the peptidic bonds was used to determine the alpha-helix, beta-sheet, and random coil content of different batches of STAT3 protein. For batches of P-STAT3, the composition was found to be 28.3% α-helix, 22.3% β-sheet and 49.4% random coils. For un-P-STAT3, the β-sheet content was slightly higher (23.2%) while the α-helix content was lower (26.8%). Next, protein:ligand interactions which alter the conformation of the protein were studied. Titration of un-P-STAT monomer with different small-molecule inhibitors produced a significant change in the CD spectrum consistent with modification of secondary structure due to altered folding. In particular, significant effects on the secondary structures of both un-P- and P-STAT3 were observed upon binding of the natural peptidic ligands LKTKF and LPQTV. Crucially, the different complex geometries adopted by the proteins upon interaction with ligands could be used to determine the stoichiometry of interaction and the orientation of the ligands in the binding pocket of the protein. These results demonstrate that CD spectroscopy can be used to evaluate STAT3 structure and ligand interactions at the molecular level, and thus represents a useful analytical tool in the development of small molecule inhibitors for potential therapeutic use. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1382. doi:10.1158/1538-7445.AM2011-1382
Tc-99m Sestamibi Imaging in the Diagnostic Assessment of Patients With Lymphomas: Comparison With Clinical and Radiological Evaluation
Authors: SIMONE MAUREA, WANDA ACAMPA, PAOLA VARRELLA, VINCENZO DE ROSA, PIETRO FIMIANI, GIUSEPPE ABATE, MARCO SALVATORE
Journal: Clinical Nuclear Medicine (1998)

Tc-99m MIBI imaging has been used in nuclear oncology, but its role in detecting lymphomas has not been widely investigated. In this study, 31 patients with lymphomas (20 non-Hodgkin's and 11 Hodgkin's) underwent Tc-99m MIBI whole-body imaging. A total of 74 tumor lesions were detected in 25 patients, while the remaining 6 patients were disease-free. The diagnostic accuracy of MIBI imaging for lesion detection was 85%. A total of 11 unknown tumor lesions in 3 patients were discovered on MIBI scans. Tumor size was significantly (p = 0.01) higher in lesions with increased MIBI uptake (3.5 ± 2.0 cm) compared with those with no uptake (1.8 ± 1.0 cm). No false positive MIBI findings were observed. The accuracy of MIBI scintigraphy in patients with Hodgkin's disease was lower (72%) compared to that of patients with non-Hodgkin's lymphomas (94%). However, this difference was not related to tumor type, but to lesion size. In fact, tumor size was significantly (p = 0.02) lower in lesions of patients with Hodgkin's disease (2.5 ± 1.3 cm) compared to those of patients with non-Hodgkin's lymphomas (3.7 ± 2.2 cm). MIBI imaging may be useful in patients with lymphomas for detecting tumor lesions and, hence, may be considered an alternative to gallium scanning, providing better imaging quality. However, the intense Sestamibi activity in the lower chest and abdomen as well as tumor size may limit the diagnostic sensitivity of this radionuclide technique in patients with lymphomas.
Abstract 3000: New epigenetic biomarker for colorectal cancer.
Authors: Kiyoko Takane, Yutaka Midorikawa, Koichi Yagi, Ayako Sakai, Hiroyuki Aburatani, Tadatoshi Takayama, Atsuhi Kaneda
Journal: Cancer Research (2013)

Abstract DNA is released and circulate in the blood of cancer patients. Epigenetic changes in the levels of circulating DNA has been associated with tumor burden and malignant progression. Public physical examination recommends occult fecal blood test for colorectal cancer (CRC) screening but its false positive rate is too high. As for serum marker for CRC including CEA and CA19-9, their sensitivity are nor satisfactory especially in early stage CRC patients and therefore, the potential use of circulating DNA for CRC screening has emerged. The aim of this study is the clinical utility of cell-free DNA as blood biomarkers. Based on our previous report about the new methylation markers for CRC on a genome-wide scale, we selected 4 methylation markers positive for CRC and established CRC screening panel. First, we collected plasma DNA from blood samples of 100 CRC patients preoperatively and 50 age-matched healthy volunteers. Then, we performed pyrosequence about plasma DNA after bisulfite treatment. Using this cancer screening panel, 82 CRC patients were positive for at least 1 marker. On the other hand, no control samples were positive for any markers and therefore, sensitivity and specificity using this cancer screening panel for CRC were 82.0% and 100%, respectively. According to TNM classification, positive rate for earlier stage including 1 and 2 patients were lower than advanced CRC patients. Similarly, the patients with abnormal serum CEA level harbored higher positive rate for the cancer panel, but serum CA19-9 level which is another CRC marker was not associated with positive rate. Two markers of the panel were relatively high in old age although they were negative for control samples. Considering that no hypermethylation was detected in control samples, this cancer panel is superior to preexisting blood tumor markers for CRC and available for cancer screening. Citation Format: Kiyoko Takane, Yutaka Midorikawa, Koichi Yagi, Ayako Sakai, Hiroyuki Aburatani, Tadatoshi Takayama, Atsuhi Kaneda. New epigenetic biomarker for colorectal cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3000. doi:10.1158/1538-7445.AM2013-3000
Improvement of Gastric Emptying in Diabetic Gastroparesis by Erythromycin
Authors: J. Janssens, T.L. Peeters, G. Vantrappen, J. Tack, J.L. Urbain, M. De Roo, E. Muls, R. Bouillon
Journal: New England Journal of Medicine (1990)

Erythromycin mimics the effect of the gastrointestinal polypeptide motilin on gastrointestinal motility, probably by binding to motilin receptors and acting as a motilin agonist. Erythromycin may thus have clinical application in patients with disturbances of gastroduodenal motility, such as diabetic gastroparesis.
Combination Therapy of Gemcitabine and 24-H Infusion of Cisplatin for Advanced Urothelial Carcinomas
Authors: K. Ina, R. Furuta, H. Totani, S. Kayukawa, S. Hibi, M. Kabeya, Y. Sirokawa, C. Koga, T. Kataoka
Journal: Annals of Oncology (2013)
Abstract 3334: Repression of mammary stem/progenitor cells by p53 is mediated by notch and separable from apoptotic activity
Authors: Luwei Tao, Amy L. Roberts, Karen A. Dunphy, Carol Bigelow, Haoheng Yan, D. Joseph Jerry
Journal: Cancer Research (2011)

Abstract Breast cancer is the most common tumor among women with inherited mutations in the p53 gene (Li-Fraumeni syndrome). The tumors represent the basal-like subtype which has been suggested to originate from mammary stem/progenitor cells. In mouse mammary epithelium, mammosphere-forming potential was increased with decreased dosage of the gene encoding the p53 tumor suppressor protein (Trp53). Limiting dilution transplantation also showed a 3.3-fold increase in the frequency of long-term regenerative mammary stem cells in Trp53-/- mice. The repression of mammospheres by p53 was apparent despite the absence of apoptotic responses to radiation indicating a dissociation of these two activities of p53. The frequency of long-term label-retaining epithelial cells (LRECs) was decreased in Trp53-/- mammary glands indicating that asymmetric segregation of DNA is diminished and contributes to the expansion of the mammary stem cells. Treatment with an inhibitor of γ-secretase (DAPT) reduced the number of Trp53-/- mammospheres to the level found in Trp53+/+ cells. These results demonstrate that basal levels of p53 restrict mammary stem/progenitor cells through Notch and that the Notch pathway is a therapeutic target to prevent expansion of this vulnerable pool of cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3334. doi:10.1158/1538-7445.AM2011-3334
Differences in breast cancer subtype distribution exist among ethnic subgroups of Asian women in California.
Authors: ML Telli, AW Kurian, ET Chang, TH Keegan, LA McClure, JM Ford, SL Gomez
Journal: Cancer Research (2009)

Abstract Abstract #2088 Background: Distinct breast cancer subtypes have been identified by gene expression analysis. Little is known about the distribution of these subtypes among Asian women. We previously reported an increased frequency of HER2-positive breast cancers among certain ethnic subgroups of Asian women in California. To follow up on that finding in detail, we undertook the current analysis to explore factors associated with differences in breast cancer subtype distribution among Asian women in California.&amp;#x2028; Methods: We defined immunohistochemical surrogates for each breast cancer subtype among Chinese, Japanese, Filipina, Korean, Vietnamese and South Asian patients in the population-based California Cancer Registry diagnosed in the period 1999-2005. Subtypes were defined using combinations of immunohistochemical markers: luminal A (ER+ and/or PR+, HER2-), luminal B (ER+ and/or PR+, HER2+), basal-like (ER-, PR-, HER2-) and HER2+/ER- (ER-, PR-, HER2+). Polytomous logistic regression was used to evaluate associations between breast cancer subtype and age, race, AJCC stage, tumor grade, tumor histology, socioeconomic status, nativity and hospital ownership (private vs. public). Models were used to compare differences in these characteristics simultaneously across the four breast cancer subtypes.&amp;#x2028; Results: Of 12,245 Asian women diagnosed with invasive breast cancer, 7,217 (59%) women had data for all three immunohistochemical markers. The majority of breast cancers among Japanese women were of the luminal A subtype (67%), with a low frequency of basal-like (10%) and HER2+ (22%) cancers. Korean, Filipina and Vietnamese women had a high frequency of HER2+ cancers (35%, 31% and 31%, respectively) compared to Non-Hispanic White women diagnosed during this period (n=12,996, 21%). In regression analyses among Asian women, the four subtypes varied significantly in their associations with age group (p=0.01), detailed Asian ethnicity (p&amp;lt;0.0001), stage (p&amp;lt;0.0001), grade (p&amp;lt;0.0001), histology (p&amp;lt;0.0001), year of diagnosis (continuous; p=0.03) and hospital ownership (p&amp;lt;0.0001). However, there was no significant variation among the subtypes in their relationships with socioeconomic status (p=0.94) or nativity (p=0.29).&amp;#x2028; Conclusions: Differences in the distribution of breast cancer subtypes exist among Asian women according to ethnicity, as well as other demographic and disease characteristics. These differences were not associated with place of birth or socioeconomic status. Breast cancers among Japanese women had the most favorable subtype distribution, while Korean women had the least favorable distribution. Further study may identify genetic and environmental risk factors responsible for these differences, with implications for prevention and treatment. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2088.
Chloromycetin in the Treatment of Pneumonia in Infants and Children
Authors: Adrian Recinos, Sidney Ross, Benett Olshaker, Ellsworth Twible
Journal: New England Journal of Medicine (1949)

CHLOROMYCETIN is an antibiotic derived from a strain of Streptomyces venezuelae. Its antimicrobial spectrum is broad and embraces the following organisms: rickettsia, certain viruses of the psittacosis group, gram-positive cocci (including the pneumococcus, streptococcus and staphylococcus) and certain gram-negative organisms including Eberthella typhosa, shigella and several of the coliform group.1 The drug is well tolerated orally, and few toxic reactions have followed its use in therapeutic doses. Chloromycetin is readily absorbed after oral administration, and blood levels of 10 to 40 mg. per 100 cc. are readily obtained when 50 to 100 mg. per kilogram of body weight . . .
P5-07-06: Effect of Angiotensin-(1-7) and Angiotensin II on T47D Breast Cancer Cells in the Proliferation and cAMP Production.
Authors: Silva IDCG da, SSAA Correa-Noronha, SMR Noronha, C Alecrim, SI Shimuta, CR Nakaie, LH Gebrim, ACP Nazario
Journal: Cancer Research (2011)

Abstract Angiotensin-(1-7) [Ang(1-7)] is a peptide hormone that produces opposite responses to those of the well-characterized peptide angiotensin II (Ang II). The main actions of Ang(1-7) and AII occur, respectively, via MAS and Angiotensin type 1 receptor (AT1R), respectively. Ang (1-7) has blood pressure and proliferative effects contrary to those of AngII, exhibits significant antiangiogenic activity and may be a novel therapeutic agent for lung cancer treatment targeting a specific AT(1-7) receptor (Soto-Pantoja et al., 2009). Here, our aim was to evaluate T47D breast cancer cell proliferation and cAMP production after treatment with Ang (1-7) and AngII.By means of the cyclic AMP (cAMP) competitive enzymeimmunoassay system we measured cAMP content of T47D cells. Cell proliferation was measured using incorporation of BrdU after Ang (1-7) and AII stimulation. Intracellular cAMP increasing drugs like Forskolin (FK) and isobutylmethylxanthine (IBMX) were also used to stimulate T47D cells.AII inhibited cAMP production (−39%) and A-(1-7) increased its formation (48%). Pattern of cAMP production was not altered when cells were previously incubated with FK. Results were inverted after IBMX incubation. In proliferation, opposite responses were observed for Ang II and Ang (1-7), that is, increasing (7.6 times) and decreasing (7.5 times) proliferation rates respectively. Also both peptides decreased proliferation when cells were stimulated by FK. Exactly the opposite happened after IBMX stimulation, both peptides increased proliferation. These results suggest that Ang (1-7) inhibits growth of T47D cells probably through inhibition of the via RAS/RAF/MAP quinase, what corroboraties previous findings. On the other hand, AngII can induce cell proliferation by an alternative via (CREB/growth factor). Therefore, Ang (1-7) seems to be not only a promising target to develop novel lung cancer therapeutic drugs, but it also might help to prevent the molecular changes that lead the normal breast epithelial cells to cancer initiation. Financial Support: FAPESP. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-07-06.
A8.3 Remission as the main target of therapy in early rheumatoid arthritis (RA) patients: comparative efficacy of four treatment regimens
Authors: E Fedorenko, G Lukina, Y Sigidin
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Early RA contains the ''the window of opportunities'' for achieving the best results of therapy including remissions. Therefore it is very important to determine the influence of different treatment strategies on the remission rate in patients (pts) with early RA. <h3>Objectives</h3> To compare development of remissions in pts with early (&lt;2 years duration) RA who were randomly assigned to receive 4 different regimens of DMARDs treatment. <h3>Methods</h3> One hundred forty-one pts with RA of less than 2 years duration (122 women, mean age 51 years, mean disease duration 24 weeks, mean DAS28 59; 64% RF-positive, 59% ACCP-positive) were randomised to receive one of the following treatment regimens: methotrexate (MTX, up to 20 mg/week, 35 pts); MTX plus prednisolone (P) 10 mg daily (MTX-P, 34 pts); MTX-P plus methylprednisolone (MP) 1000 mg intravenously on the first day of treatment (MTX-P-MP, 35 pts); leflunomide 20 mg daily (LEF, 37 pts). Duration of treatment was one year. Control points were 3, 6 and 12 months from the initiation of therapy. Efficacy of therapy was assessed by EULAR criteria. The primary endpoint was the development of remission. <h3>Results</h3> At baseline all groups were comparable in their demographic, clinical and radiographic characteristics. One hundred twenty-seven pts completed the study. By the 3-d month in the MTX group only 3.1% of the patients reached clinical remission, while in the combination groups of MTX with GC (including MP intravenously) 21.3% and 28.6%, respectively. By the 6-th month the same tendency continued: combination of MTX with GC showed the greatest frequency of remissions – 33.3% and 23.5%, respectively. In the MTX and LEF monotherapy groups the corresponding figures were15.2% and 20.6%, respectively. At the end of the treatment (by the 12-th month) the frequency of remissions was significantly higher in pts treated with the combination of MTX and GC, including high doses of MP (37.5% and 29.4%, respectively) than in the MTX and LEF monotherapy groups (11.4% and 16.2%, respectively). <h3>Conclusions</h3> In pts with early RA combined treatment with MTX and GC led to the significantly higher remission rate as compared with MTX and LEF monotherapy.
P4-11-12: Molecular Phenotype of Breast Cancers in a Large Cohort of Young Women According to Time Interval Since Pregnancy.
Authors: LC Collins, S Gelber, JD Marotti, K Cole, S Kereakoglow, KJ Ruddy, EF Brachtel, L Schapira, SE Come, VF Borges, PJ Schedin, E Warner, E Winer, A Partridge
Journal: Cancer Research (2011)

Abstract Background: The increase in breast cancer risk during pregnancy and post partum is well recognized. The cross-over to protective effect does not occur until many years later and varies with age at first birth. Recently, a genomic signature specific to the pregnant compared with the non-pregnant breast has been identified; this signature remains present in the postmenopausal parous breast. Given this, we investigated whether time interval since pregnancy affects the phenotype of breast cancers arising in young women compared with nulliparous women. Methods: We examined molecular phenotype, according to histologic grade and biomarker status, in relation to time since pregnancy in an ongoing prospective cohort study (n=355) of young women (≤40yrs) with breast cancer. Medical records were reviewed for tumor stage and receptor status. Parity was ascertained from questionnaires completed within 9 months of diagnosis. Tumor grade was determined by central pathology review. Using tumor grade and biomarker expression, cancers were categorized as luminal A (ER+ and/or PR+, HER2−, histologic grade 1 or 2); luminal B ( ER+ and/or PR+, HER2+, or ER and/or PR+, HER2− and grade 3); HER2 type (ER-, PR-, HER2+); and triple negative (ER-, PR-, HER2−). Results: The median age of the study population is 37 years (range 17–40). Overall, 80% of women had stage 1 or 2 disease; 67% of cancers were ER positive and 32% showed HER2 overexpression. The distribution of breast cancer molecular phenotypes by time interval since last pregnancy is shown in the table. Distribution of molecular phenotype by interval between last pregnancy and diagnosis In our large cohort of parous young women, we found no differences in the distribution of molecular phenotype according to time interval since pregnancy. However, nulliparous young women were more likely to develop luminal A cancers compared to parous women (40% vs. 29%; unadjusted chi square p-value=0.03) and appeared less likely to develop HER2−type and triple negative cancers (7% vs. 13%, p-value=0.09 and 17% vs. 23%, p-value=0.22 respectively). There were no differences in the distribution of luminal B cancers. Conclusions: The distribution of molecular phenotypes is similar among parous young women regardless of the time interval since parturition. Nulliparous young women appear more likely to develop luminal A cancers compared to parous women. Whether the difference in molecular phenotypes of pregnancy-associated breast cancers vs. cancers arising in nulliparous women is due to the effects of genomic alteration remains to be investigated. Effects of a prior pregnancy appear consistent across a 5-year period, in keeping with the concept of genomic alterations identified in the normal pregnant breast and thereafter. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-11-12.