tbuckley/cabot-search huggingface dataset:
Experimental Chemotherapy (L1210) With 5-Aza-2′-deoxycytidine in Combination With Pyran Copolymer (MVE-4), an Immune Adjuvant
Authors: D S Zaharko, J M Covey, C C Muneses
Journal: JNCI Journal of the National Cancer Institute (1985)

The life-span of CDF1 (BALB/C × DBA/2)F1 mice that received intraperitoneal implants with 105 L1210 tumor cells was prolonged to 23 days (compared to 8 days in L1210 tumor-implanted, untreated mice) when 5-aza-2′-deoxycytidine (DAC) was given to the mice after the tumor cells were allowed to metastasize (3 days after implant); DAC, however, resulted in no cures (survival beyond 48 days). When the pyran copolymer MVE-4, an immune adjuvant, was given the day after DAC, 25% of the mice treated were cured and the life-span of dying mice was increased by 7 days. When MVE-4 was repeated weekly for 4 weeks, 79% of treated mice were cured. Cured mice were able to resist a subsequent challenge of approximateoy 2 logs of L1210 cells. This combination of DAC plus MVE-4 was more effective than DAC alone only if the tumor cells and MVE-4 were given intraperitoneally. When this combination was repeated weekly, it became lethally toxic after 3 weeks, but only to L1210-tumor-bearing mice and not to normal mice. When DAC alone was given 2 days before tumor implant, it induced an apparent immune effect so that mice could resist a subsequent challenge of approximately 1.5–2 logs of L1210 cells. Support for part of the antitumor action of DAC exerted through the immune system was given by data that show that later treatment with noncurative doses of DAC is superior to early treatment in mice with large L1210 tumor burdens.
Expression of key signaling molecules in resected pancreatic cancer
Authors: M. Resnick, M. Cohen-Uram, B. Smith, D. Iannitti, S. Reinert, A. Rosmarin, H. Safran
Journal: Journal of Clinical Oncology (2004)

9679 Background: Epidermal Growth Factor Receptor (EGFR) inhibitors are promising therapeutic compounds in gastrointestinal malignancies and other cancers, but predictors of response to these agents are currently undefined. Mediators of signal transduction pathways may predict response to therapy, but there are no comprehensive reports of their expression or activation in a well-defined cohort of patients with pancreatic cancer. Recently, it has been suggested that IGFR-I signaling through phosphoinositide 3-kinase may represent a novel and potentially important mechanism of resistance to anti-EGFR therapy. Methods: We performed a retrospective immunohistochemical analysis of tissue arrays derived from 69 archival specimens of resected pancreatic cancer from Rhode Island Hospital, The Miriam Hospital, and other Brown University Oncology Group (BrUOG)-affiliated institutions between the years of 1992–2003. Monoclonal antibodies or polyclonal antisera directed against the following molecules were used to interrogate the tissue microarrays: EGFR, Insulin-like Growth Factor Receptor (IGFR), AKT, and activated ERK (phospho-ERK). Results: Kaplan-Meier survival curves demonstrated a median survival of approximately 500 days. There was no statistically significant correlation of any of the above parameters with survival. Conclusions: There was no clear correlation of expression of signaling molecules with stage or grade of disease, or with survival. These studies suggest that these signaling pathways are frequently activated in pancreatic cancer and these signaling molecules may provide novel, therapeutic targets for this disease. No significant financial relationships to disclose.
Detection of disseminated epithelial cells in patients with breast cancer: comparison of blood and bone marrow for CK19 en MAM mRNA expression
Authors: I. Benoy, H. Elst, I. dan der Auwera, S. van Laere, G. dan den Eynden, P. van Dam, E. van Marck, P. Vermeulen, L. Dirix
Journal: Journal of Clinical Oncology (2005)

9539 Background: Although current adjuvant therapies in patients with breast cancer (BC) are individualized according to different prognostic and predictive factors, current recommendations fail to accurately identify the population at risk. Detection of minimal disease at distant sites is one option to individualize treatment strategies. Detection of tumour cells in bone marrow (BM) is an obvious choice in BC, but blood sampling is more convenient. The aim of this study was to compare blood (PB) and BM for the detection of disseminated epithelial cells (DEC). Methods: PB and BM samples were collected from 149 patients with BC. DEC were detected by measuring relative gene expression (RGE) for CK-19 and MAM using a quantitative RT-PCR detection method. Results: Elevated BM CK-19 expression was detected in 69% of patients with advanced BC (M+). PB samples of these patients tested positive for CK-19 expression in 32% of the cases. CK-19 RGE in primary non-metastatic patients (M0) was increased in 12% and 53% of the PB and BM samples. MAM expression was elevated in 6% (PB) and 15% (BM) of the M0 group and in 42% (PB) and 38% (BM) of the M+ group. A significant correlation was found for CK-19 and MAM RGE comparing PB and BM samples (CK-19: Spearman Rho=0,4, p=0,003/MAM: Spearman Rho=0,3, p=0,002). There was a 54% (CK-19) and 85% (MAM) concordance between PB and BM samples. The Kappa value is slight for CK-19 expression (0, 152) and according to McNemar statistics there is a significant difference between PB and BM (p<0,0001). The Kappa value for MAM expression is moderate (0,41) and there is no difference according to McNemar (p=0,21). Conclusion: We observed higher detection rates of DEC in BM samples than in peripheral PB samples. DEC may indeed not circulate continuously, and the small volume of PB may result in sampling error. The occurrence of DEC in the BM of patients with BC is probably less time-dependent and may also act as a filter for circulating breast cancer cells. Statistically, no association is found between CK-19 expression in PB and in BM. No significant financial relationships to disclose.
Different systolic blood pressure targets for people with history of stroke or transient ischaemic attack: PAST-BP (Prevention After Stroke—Blood Pressure) randomised controlled trial
Authors: Jonathan Mant, Richard J McManus, Andrea Roalfe, Kate Fletcher, Clare J Taylor, Una Martin, Satnam Virdee, Sheila Greenfield, F D Richard Hobbs
Journal: BMJ (2016)

<b>Objective</b>&nbsp;To assess whether using intensive blood pressure targets leads to lower blood pressure in a community population of people with prevalent cerebrovascular disease. <b>Design</b>&nbsp;Open label randomised controlled trial. <b>Setting</b>&nbsp;99 general practices in England, with participants recruited in 2009-11. <b>Participants</b>&nbsp;People with a history of stroke or transient ischaemic attack whose systolic blood pressure was 125 mm Hg or above. <b>Interventions</b>&nbsp;Intensive systolic blood pressure target (&lt;130 mm Hg or 10 mm Hg reduction from baseline if this was &lt;140 mm Hg) or standard target (&lt;140 mm Hg). Apart from the different target, patients in both arms were actively managed in the same way with regular reviews by the primary care team. <b>Main outcome measure</b>&nbsp;Change in systolic blood pressure between baseline and 12 months. <b>Results</b>&nbsp;529 patients (mean age 72) were enrolled, 266 to the intensive target arm and 263 to the standard target arm, of whom 379 were included in the primary analysis (182 (68%) intensive arm; 197 (75%) standard arm). 84 patients withdrew from the study during the follow-up period (52 intensive arm; 32 standard arm). Mean systolic blood pressure dropped by 16.1 mm Hg to 127.4 mm Hg in the intensive target arm and by 12.8 mm Hg to 129.4 mm Hg in the standard arm (difference between groups 2.9 (95% confidence interval 0.2 to 5.7) mm Hg; P=0.03). <b>Conclusions</b>&nbsp;Aiming for target below 130 mm Hg rather than 140 mm Hg for systolic blood pressure in people with cerebrovascular disease in primary care led to a small additional reduction in blood pressure. Active management of systolic blood pressure in this population using a &lt;140 mm Hg target led to a clinically important reduction in blood pressure. <b>Trial registration</b>&nbsp;Current Controlled Trials ISRCTN29062286.
Impact of PIK3CA mutations and p95HER2 expression on the outcome of HER2-positive metastatic breast cancer patients treated with a trastuzumab-based therapy.
Authors: Andrea Fontana, Giacomo Allegrini, Mazhar al Zoubi, Paola Collecchi, Chiara Mazzanti, Irene Stasi, Sara Lucchesi, Eleonora Bona, Ilaria Ferrarini, Barbara Salvadori, Giada Arrighi, Lorenzo Marcucci, Mario Filidei, Cinzia Orlandini, Alfredo Falcone, Generoso Bevilacqua, Katia Zavaglia
Journal: Journal of Clinical Oncology (2012)

629 Background: Currently, no biomarkers of trastuzumab (T) clinical resistance have been validated. The aim of this pilot study was to evaluate the impact of PIK3CA mutations and p95HER2 (pHER2 truncated form) expression on the efficacy of a T based-therapy in a HER2-positive metastatic breast cancer (MBC) patients (pts). Methods: 107 HER2-positive MBC pts, treated in the last 10 years, were evaluated. Median age was 54 years (25-79); ECOG performance status was 0 in 56% of pts; all pts received several lines of treatment including T; biomarkers molecular analysis was performed in 70 tumor specimens. The IHC expression of p95HER2 was evaluated by a monoclonal antibody that specifically recognizes only the HER2 external domain; the HER2 integrity was defined by the presence of a homogeneous membrane staining (moderate or intense) in at least 30% of the cells, otherwise the HER2 was defined as p95HER2 positive. PIK3CA mutations in exons 9 and 20 were detected by automated sequencing. The molecular data were correlated to Time to progression (TTP) of the first line treatment including T and the Overall Survival (OS) by using the Kaplan-Meir method and the log-rank-test. Results: p95HER2 positive pts and PIK3CA mutations in exon 9 or 20 were detected in 42% and 22% of tumor specimens, respectively. p95HER2 positive tumors showed a shorter TTP and OS that did not reach statistical significance; PIK3CA mutations correlated with a worse TTP (median 7,6 vs 11,3 months) and OS (median 20,1 vs 41,0 months, p= 0,046). Conclusions: These preliminary results suggest a possible role of PIK3CA mutational status in predicting the outcome of MBC pts treated with T.
Feasibility of ovarian preservation in patients with early stage endometrial carcinoma: A retrospective study
Authors: T. Lee, J. Jung, J. Kim, J. Kim, N. Park, Y. Song, S. Kang, H. Lee
Journal: Journal of Clinical Oncology (2006)

15064 Background: The treatment of endometrial cancer involves surgical removal of the ovary; this elimination induces an abrupt menopause and may deteriorate the qualities of life. Therefore, ovarian preservation may be a consideration for premenopausal women. Our main objectives are to examine the occurrence of ovarian metastasis or synchronous malignancy and to evaluate the feasibility of ovarian preservation in patients with early stage endometrial carcinoma. Methods: We reviewed the medical records of 259 patients undergoing surgical treatment for endometrial cancer at a single institute from 1992 to 2004. Results: Among the 224 patients with endometrial adenocarcinoma who had undergone ovarian removal, cancer in ovarian tissue was detected in 21 cases (9.4%, 14 ovarian metastasis, 7 synchronous cancer). Synchronous ovarian cancer showed abnormal gross finding in all 7 cases. Thirteen cases of ovarian metastasis were high grade lesion in preoperative evaluation, or showed intraoperative peritoneal seeding or abnormal gross lesion around adnexa. In 35 patients, grossly normal ovary was saved selectively in compliance with patients’ need (19 bilateral, 16 unilateral). Thirty-one of 35 (89%) were under 45 years and mostly showed early stage (Ia, 24; Ib, 7; Ic, 1; IIa, 1; IIb, 2). Pre-operative MRI was available in 30 cases, and none of them showed findings suggesting tumor extension outside of uterus. In 2 cases of IIb, postoperative radiation therapy was done. There was no recurrence or death in all cases of ovarian preservation except one in which a patient died of sepsis caused by postoperative bowel perforation (median duration of follow-up, 76 mon.; range 3∼121). Conclusions: Ovarian preservation can be cautiously performed, preceded by a thorough preoperative and intraoperative assessment of the adnexa in young women with endometrial carcinoma. The patients who desire ovarian preservation should be counseled regarding the rate of ovarian metastasis or synchronous malignancy. No significant financial relationships to disclose.
Abstract P308: {gamma}-Glutamyltransferase and Mortality from Cardiovascular Disease: EPOCH-JAPAN
Authors: Yuanying Li, Hiroyasu Iso, Renze Cui, Shinya Nagasawa, Yoshitaka Murakami, Katsuyuki Miura, Hirotsugu Ueshima, Tomonori Okamura
Journal: Circulation (2012)

Background: Recently, γ-Glutamyltransferase (γ-GTP) has been positively associated with risk of cardiovascular disease (CVD), especially among non-drinkers. But the evidence is limited in Asian pop...
Successful Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplant in an Acute Leukemia Patient With Chemotherapy-Induced Marrow Aplasia and Progressive Pulmonary Aspergillosis
Authors: Chang Q. Xun, Peter A. McSweeney, Michael Boeckh, Rainer F. Storb, Virginia C. Broudy, John A. Thompson
Journal: Blood (1999)
Effect of hematologic improvement (HI) on survival in patients (pts) given targeted therapy (TT) as initial treatment of acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (HR-MDS)
Authors: M. Yanada, X. Huang, S. O'Brien, G. Garcia-Manero, F. Ravandi, G. Borthakur, J. Issa, F. Giles, H. Kantarjian, E. Estey
Journal: Journal of Clinical Oncology (2007)

7059 Background: Recent years have seen the introduction of TT for pts with AML and HR- MDS (&gt; 10% marrow blasts). New criteria, less stringent than those for CR, for response to these agents have been promulgated, giving rise to the response category HI. However, the effect of achieving HI on survival is uncertain. Methods: 180 pts, median age 73, with AML or HR-MDS received TT, most commonly decitabine (69 pts), from 2000–2006. Treatment-related death occurred in 11%, CR in 28%, CRp in 6%, and 55% (99 pts) were resistant. We examined survival in these 99 according to whether TT produced HI, blood count criteria for which were as defined by the International Working Group (IWG) for MDS. Initially, we, unlike the IWG, did not require any duration of HI, however; in subsequent analyses, we required durations of = 4 weeks (HI-4) and, like the IWG, = 8 weeks (HI-8). Results: Survival time dated from start of TT was similar in the 32 pts who achieved HI and the 67 who did not. However, the 13 pts with HI-8 lived longer than those with shorter or no HI (48% vs. 11% at 2 years, p=0.01) as did the 14 with HI-4 (p=0.01). Because HI-4 and HI-8 pts had to live long enough to achieve and maintain HI, we re-did the analysis including only the 84 pts who lived = 67 days from start of TT, the median time needed to observe HI-4. This analysis, which included HI-4, age, and cytogenetics as predictors of survival, indicated that HI-4 was the strongest predictor of longer survival (HR 0.34, 95% CI 0.13–0.86, p=0.02). Results were analogous when we limited the analysis to the 68 pts who lived at least 138 days, by which time 75% of HI-4 pts had achieved HI (p=0.06). Conclusions: Our results suggest that HI-4 (or HI-8 as defined by the IWG) following TT confers a survival benefit in AML or HR-MDS. No significant financial relationships to disclose.
EGFR mutations and the correlation with gefitinib therapy in Chinese NSCLC—A systematic review based on individual patient data from 5 medical centers in China
Authors: Y. Wu, W. Zhong, L. Li, L. Zhang, C. Zhou, W. Liu, J. Lin, Q. Zhou, C. Xu, G. Zhang, T. Mok
Journal: Journal of Clinical Oncology (2006)

7187 Background: EGFR mutations were found to have a significant association with response to gefitinib. To date, information on status of EGFR mutation in Chinese remains scanty. Comprehensive review of existing information on EGFR mutations is essential for treatment selection in Chinese patients with advanced NSCLC. Methods: We published 4 abstracts on EGFR mutation in Chinese patients at the 41st ASCO. We performed an IPD-meta-analysis on the data from the above investigators plus another one. The original individual EGFR mutations (exon 18,19,21) data was collected. Gefitinib was given with 250 mg/d until disease progression. Results: Total 407 cases were into the IPD review. The patient characteristic was male: female = 258:149; adenocarcinoma: other = 259:148; smoker: nonsmoker =178:153. The EGFR mutation rate was 3.05% (124/407). For adeno subgroup the EGFR mutation rate was 42.5% (110/259), non- adeno was 9.5% (14/148). In female the EGFR mutation rate was 41.6% (62/149), male was 24.0% (62/258). Non-smoker was 39.2% (60/153), smoker was 18.5% (33/178). In univariate analysis adeno, smoking, gender was significant predictive factors for EGFR mutation but in logistic regression only adeno is independent correlation factor (p = 0.000, 95% CI 2.078—9.001). Conclusions: The EGFR mutation is more common in no-smoking female adeno patients with NSCLC. The EGFR mutation group has a tendency of response rate to gefitinib compare to the EGFR wild group in NSCLC patients. [Table: see text] No significant financial relationships to disclose.
Herbacetin Is a Novel Allosteric Inhibitor of Ornithine Decarboxylase with Antitumor Activity
Authors: Dong Joon Kim, Eunmiri Roh, Mee-Hyun Lee, Naomi Oi, Do Young Lim, Myoung Ok Kim, Yong-Yeon Cho, Angelo Pugliese, Jung-Hyun Shim, Hanyong Chen, Eun Jin Cho, Jong-Eun Kim, Sun Chul Kang, Souren Paul, Hee Eun Kang, Ji Won Jung, Sung-Young Lee, Sung-Hyun Kim, Kanamata Reddy, Young Il Yeom, Ann M. Bode, Zigang Dong
Journal: Cancer Research (2015)

Ornithine decarboxylase (ODC) is a rate-limiting enzyme in the first step of polyamine biosynthesis that is associated with cell growth and tumor formation. Existing catalytic inhibitors of ODC have lacked efficacy in clinical testing or displayed unacceptable toxicity. In this study, we report the identification of an effective and nontoxic allosteric inhibitor of ODC. Using computer docking simulation and an in vitro ODC enzyme assay, we identified herbacetin, a natural compound found in flax and other plants, as a novel ODC inhibitor. Mechanistic investigations defined aspartate 44 in ODC as critical for binding. Herbacetin exhibited potent anticancer activity in colon cancer cell lines expressing high levels of ODC. Intraperitoneal or oral administration of herbacetin effectively suppressed HCT116 xenograft tumor growth and also reduced the number and size of polyps in a mouse model of APC-driven colon cancer (ApcMin/+). Unlike the well-established ODC inhibitor DFMO, herbacetin treatment was not associated with hearing loss. Taken together, our findings defined the natural product herbacetin as an allosteric inhibitor of ODC with chemopreventive and antitumor activity in preclinical models of colon cancer, prompting its further investigation in clinical trials.
Exercise and pregnancy: focus on advice for the competitive and elite athlete
Authors: Uğur Erdener, Richard Budgett
Journal: British Journal of Sports Medicine (2016)

Athletes’ safety is a top priority of the IOC, and the IOC Medical and Scientific Commission aims to reach evidence-based consensus on debatable topics. There are several guidelines regarding physical activity and exercise during pregnancy and postpartum period (American College of Obstetrician and Gynecologists, Canadian Society of Exercise Physiologists and Society of Obstetricians and Gynecologist of Canada, American College of Sports Medicine, The Royal College of Obstetricians and Gynecologists). However, until the IOC consensus meeting in September 2015, there was not any consensus statement on “Exercise in Pregnancy and the Post-partum Period in elite sports particularly for High-level Athletes”.1

The IOC consensus meeting had two aims: (1) to comprehensively review risk factors related to different physical and physiological states of a pregnant athlete and (2) to provide recommendations for training and competing during pregnancy and postpartum period for high levels athletes.

As IOC President Bach emphasised, “Sport is not just …
Targeting fanconi anemia (FA) repair pathway deficiency for treatment with PARP inhibitors.
Authors: W. Zhao, W. Duan, M. E. Leon, A. P. Chen, G. Sofletea, J. Thurmond, B. Ramaswamy, D. O'Malley, T. S. Bekaii-Saab, M. A. Villalona- Calero
Journal: Journal of Clinical Oncology (2010)

TPS168 Background: BRCA gene deficiency has been noted as a predictor of response to poly ADP-ribose polymerase (PARP) inhibitors. Although the numbers of cancer patients with germ line BRCA deficiency are low, BRCA is one of several genes that collaborate in the FA repair pathway. We have developed an immunofluorescence-based method to evaluate somatic functionality of the pathway (FancD2 foci formation) in paraffin-embedded tumor tissues, and hypothesized that across different histologies we could identify patients more suitable for treatment with PARP inhibitors. Methods: A two-step clinical trial was designed to 1) identify patients with solid tumors based on absence of FancD2 foci formation in their tumors, and 2) offer treatment with the PARP inhibitor ABT-888 either alone or in combination with chemotherapy at escalating doses. The tissue sections were incubated with a primary antibody cocktail of rabbit polyclonal FancD2 antibody and a monoclonal anti-Ki67 mouse antibody, followed by co-incubation with a secondary antibody (FITC conjugated to anti-rabbit IgG and Alexafluor 594 donkey anti-mouse), mounted on glass slides in a DAPI–containing embedding medium, and evaluated with a fluorescence microscope. FancD2 foci (+) and (- ) verified patients' tumor specimens in FFPE were run as controls. Absence of nuclear FancD2 foci formation in 100 proliferating cells was required for eligibility for step 2. Other correlatives include BRCA sequencing, FancD2 foci formation and gamma-H2AX in PBMC. Enrollment: 64 patients' tumors have been analyzed, including: NSC lung (12), SC lung (4), breast (14), ovarian (6), pancreatic (4), colon (5), prostate (2), head/neck (3), endometrial (3), thymus (2), gallbladder (2), and pleura, small bowel, bladder, adrenal, cervical, salivary gland, and unknown primary (1 each). 13 FancD2 deficient tumors (20%) included breast (4), ovarian (2), and NSC lung, SC lung, thymus, adrenal, small bowel, colon and unknown primary (1 each). 4 patients have initiated treatment. Therefore, a substantial amount of cancer patients have somatic deficiency in the FA pathway. The ongoing clinical trial will help determine if these patients are more susceptible to PARP inhibitor treatment. No significant financial relationships to disclose.