tbuckley/cabot-search huggingface dataset:
Cognitive Complaints in Survivors of Breast Cancer After Chemotherapy Compared With Age-Matched Controls: An Analysis From a Nationwide, Multicenter, Prospective Longitudinal Study
Authors: Michelle C. Janelsins, Charles E. Heckler, Luke J. Peppone, Charles Kamen, Karen M. Mustian, Supriya G. Mohile, Allison Magnuson, Ian R. Kleckner, Joseph J. Guido, Kelley L. Young, Alison K. Conlin, Lora R. Weiselberg, Jerry W. Mitchell, Christine A. Ambrosone, Tim A. Ahles, Gary R. Morrow
Journal: Journal of Clinical Oncology (2017)

Purpose Cancer-related cognitive impairment is an important problem for patients with breast cancer, yet its trajectory is not fully understood. Some previous cancer-related cognitive impairment research is limited by heterogeneous populations, small samples, lack of prechemotherapy and longitudinal assessments, use of normative data, and lack of generalizability. We addressed these limitations in a large prospective, longitudinal, nationwide study. Patients and Methods Patients with breast cancer from community oncology clinics and age-matched noncancer controls completed the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) at prechemotherapy and postchemotherapy and at a 6-month follow-up as an a priori exploratory aim. Longitudinal models compared FACT-Cog scores between patients and controls at the three assessments and adjusted for age, education, race, menopausal status, and baseline reading ability, anxiety, and depressive symptoms. A minimal clinically important difference cutoff determined percentages of impairment over time. Results Of patients, 581 patients with breast cancer (mean age, 53 years; 48% anthracycline-based regimens) and 364 controls (mean age, 53 years) were assessed. Patients reported significantly greater cognitive difficulties on the FACT-Cog total score and four subscales from prechemotherapy to postchemotherapy compared with controls as well as from prechemotherapy to 6-month follow-up (all P &lt; .001). Increased baseline anxiety, depression, and decreased cognitive reserve were significantly associated with lower FACT-Cog total scores. Treatment regimen, hormone, or radiation therapy was not significantly associated with FACT-Cog total scores in patients from postchemotherapy to 6-month follow-up. Patients were more likely to report a clinically significant decline in self-reported cognitive function than were controls from prechemotherapy to postchemotherapy (45.2% v 10.4%) and from prechemotherapy to 6-month follow-up (36.5% v 13.6%). Conclusion Patients with breast cancer who were treated in community oncology clinics report substantially more cognitive difficulties up to 6 months after treatment with chemotherapy than do age-matched noncancer controls.
Abstract LB-083: Regulation of the mitotic centrosome by heat shock protein 70
Authors: Chieh-Ting Fang, Hsiao-Hui Kuo, Ling-Huei Yih
Journal: Cancer Research (2015)

Abstract A functional centrosome is essential for the assembly of a bipolar mitotic spindle and accurate chromosome segregation. Loss of centrosome integrity frequently occurs in transformed cells or in tumor tissues. Pathways maintaining the quality control of proteins are known to regulate the biogenesis and duplication of the centrosome. In this study, we explored the role of heat shock protein 70 (HSP70), an essential molecular chaperone for protein quality control, on maintaining the centrosome integrity during mitosis by treating cells with a HSP70 inhibitor or transducing cells with HSP70-specific shRNA. The effects of these treatments on mitosis progression, mitotic spindle assembly, and cell viability were investigated. Our results showed that inhibition or depletion of HSP70 disrupted microtubule nucleation and polymerization, induced abnormal mitotic spindles, and interfered with mitosis progression. In addition, HSP70 accumulated at the spindle pole and co-localized with γ-tubulin and pericentrin during mitosis. Loss of centrosomal HSP70 impeded the recruitment of pericentriolar components essential for centrosome maturation. These results indicate that HSP70 is required for the maintenance of a functional mitotic centrosome to support the assembly a bipolar mitotic spindle. Citation Format: Chieh-Ting Fang, Hsiao-Hui Kuo, Ling-Huei Yih. Regulation of the mitotic centrosome by heat shock protein 70. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-083. doi:10.1158/1538-7445.AM2015-LB-083
Survival of Patients Diagnosed with Primary Refractory and Relapsed Acute Myeloid Leukemia from 2008-2012: A Single Institution Experience
Authors: Simon B. Zeichner, Shannon Gleason, Ana G. Antun, Amelia Langston, Leonard T Heffner, Vamsi K Kota, Manila Gaddh, Martha Arellano
Journal: Blood (2015)
A Rapidly Expanding Scalp Mass
Authors: Ruth J. Davis, Shih-Chun Lin, Wojciech K. Mydlarz
Journal: JAMA Oncology (2016)

A woman in her 80s presented with a 2-week history of an enlarging left parietal scalp mass that continued to enlarge. She subsequently developed progressive generalized weakness, slowed speech, and focal right-handed weakness. What is your diagnosis?
Results of the first national public breast cancer screening program in the Kingdom of Saudi Arabia
Authors: A. Omalkhair, F. Tahan, A. Al Naeem, S. Young, S. Musaad, A. Jazieh
Journal: Journal of Clinical Oncology (2009)

1524 Background: Despite the relatively low incidence in the Kingdom of Saudi Arabia (KSA) compared to Western countries, breast cancer (BC) is the most common cancer among Saudi females for the past 11 consecutive years (National Cancer Registry 1994–2004). The objective of this study is to report the results of the first public national BC screening program in KSA and to evaluate the relationship between imaging and pathological findings and known BC risk factors. Methods: Asymptomatic women 40 years of age or older underwent BC screening at Abdulatif Charitable Cancer Screening Center, Riyadh, KSA. Mammograms were scored using American College of Radiology Breast Imaging Reports and Data System (BIRADS). Correlations between imaging findings and risk factors, as well as pathological findings, were analyzed. Results: A total of 1,215 women were enrolled between September 2007 and April 2008. Median age was 45 years (19–91) and median body mass index (BMI) was 31.6 kg/m 2 (16.7–58). A total of 16 cases of cancer were diagnosed (80% are less than stage IIB). No cancer was diagnosed in 942 women with R1/R2 scores and only one case of cancer was diagnosed in 228 women with R0/R3 scores. However, among 26 women with R4/R5 scores, 50% had malignant disease and 35% had benign lesions (odds ratio = 1.96; 95% confidence interval = 1.5, 2.6) (p &lt; 0.0001). No correlation between known risk factors and imaging score or cancer diagnosis. Conclusions: The public acceptance of BC screening program was encouraging. Longitudinal follow-up and inclusion of more participants will help in better determining the risk factors relevant to our patient population. No significant financial relationships to disclose.
Acute skin and hair symptoms followed by severe, delayed eye complications in subjects using the synthetic opioid MT-45
Authors: A. Helander, M. Bradley, A. Hasselblad, L. Norlén, I. Vassilaki, M. Bäckberg, J. Lapins
Journal: British Journal of Dermatology (2016)

The introduction of unclassified new psychoactive substances (NPS) on the recreational drugs market through open online sale ('legal highs' or 'Internet drugs') continues unabated and represents a growing health hazard. The use of NPS has resulted in numerous, severe, adverse events and fatalities, due to unintended overdose or unknown toxic side‐effects. To try to find a possible common underlying cause for the skin–hair–eye symptoms complex observed in three men. From late 2013 to mid‐2014, three Swedish men aged 23–34 years with a history of recreational drug use independently presented with similar and very remarkable clinical signs, requiring extensive examination and prolonged treatment. Common clinical signs included hair depigmentation, hair loss, widespread folliculitis and dermatitis, painful intertriginous dermatitis, dry eyes, and elevated liver enzymes. Two of them also showed transverse white Mees' lines (leukonychia striata) on the fingernails and toenails, suggesting a temporary, drug‐induced, disorganized keratinization. The clinical signs gradually disappeared over time. However, later on, two developed severe bilateral secondary cataracts requiring surgery. Because drug tests within the Swedish STRIDA project had demonstrated intake of the NPS opioid MT‐45 in all patients, this was suspected to be the common causative agent. These cases highlight the importance for physicians and health professionals to consider the increasing number of novel, untested recreational drugs, as a potential cause of unusual and otherwise unrecognized clinical signs and symptoms.
Abstract 998: Induction of non-protective autophagy by radiation in tumor cells: Implications for autophagy inhibition as a therapeutic strategy
Authors: Shweta Chakradeo, Khushboo Sharma, Aisha Alhaddad, Duaa Bakhshwin, Ngoc Le, Hisashi Harada, W. Andrew Yeudall, Suzy Torti, Frank Torti, David Gewirtz
Journal: Cancer Research (2015)

Abstract Our laboratory has previously described the four functional forms of autophagy, specifically cytoprotective, cytotoxic, cytostatic and nonprotective (Gewirtz DA, Cancer Research 2014). Evidence for the nonprotective form was based on studies where murine 4T1 breast tumor cells failed to be sensitized to ionizing radiation by pharmacological or genetic inhibition of autophagy (Bristol ML, JPET, 2013). To determine whether radiation induces the cytoprotective and nonprotective forms of autophagy in human tumor cells lines of different tissue origin, the influence of autophagy inhibition on radiation sensitivity was studied in human breast, head and neck and non-small cell lung cancer cell lines. In order to examine the potential involvement of p53 in the protective and nonprotective forms of autophagy, the impact of autophagy inhibition on radiation sensitivity was compared in cell lines that were either wild type or mutant/null in p53. While ionizing radiation promoted autophagy in all tumor cell lines studied, autophagy inhibition resulted in radiation sensitivity only in the p53 wild type A549 and H460 NSCLC cells and the HN30 head and neck tumor cells. In contrast, pharmacological inhibition of autophagy and/or genetic silencing of autophagy genes failed to influence sensitivity to radiation in the p53 mutant Hs578t breast tumor cells, the HN6 head and neck tumor cells, and the H358 non-small cell lung cancer cells, indicative of nonprotective autophagy. The apparent requirement for functional p53 in the promotion of cytoprotective autophagy by radiation was confirmed by the observation that radiation induced autophagy was nonprotective in p53 null H1299 cells but was converted to the cytoprotective form with induction of p53. Conversely, whereas p53 wild-type HN30 cells did show sensitization to radiation upon autophagy inhibition HN30 cells in which p53 was knocked down were not sensitized. These observations have implications for efforts to modulate the response of malignancies to radiation (and possibly also to cancer chemotherapeutic drugs) through autophagy inhibition. Citation Format: Shweta Chakradeo, Khushboo Sharma, Aisha Alhaddad, Duaa Bakhshwin, Ngoc Le, Hisashi Harada, W. Andrew Yeudall, Suzy Torti, Frank Torti, David Gewirtz. Induction of non-protective autophagy by radiation in tumor cells: Implications for autophagy inhibition as a therapeutic strategy. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 998. doi:10.1158/1538-7445.AM2015-998
Immunohistochemical Expression Pattern of Programmed Cell Death Ligand 1 Might be Both Good and Bad Prognostic Factor in Adult T-Cell Leukemia/ Lymphoma
Authors: Miyoshi Hiroaki, Junichi Kiyasu, Takeharu Kato, Noriaki Yoshida, Daisuke Kurita, Sasaki Yuya, Koji Kato, Yoshitaka Imaizumi, Masao Seto, Koichi Akashi, Koichi Ohshima
Journal: Blood (2015)
The Effect of Pravastatin on Expression of Platelet-Derived Endothelial Nitric Oxide Synthase(eNOS) m-RNA and Atherosclerosis Course in Rabbits.
Authors: Liping Ma, Mafei Kang, Songmei Yin, Danian Nie, Shuangfen Xi, Yudan Wu, Lizhuo Xue
Journal: Blood (2004)
Abstract 3846: DNA double-strand breaks in hypoxic but not in normoxic conditions determine different radiosensitivity of tumors
Authors: Kazuhiro Ogi, Mayumi Kawata, Takafumi Nakagaki, Kousuke Takeda, Miyazaki Akihiro, Hiratsuka Hiroyoshi
Journal: Cancer Research (2015)

Abstract Purpose: While only few biomarkers like tumor histology and stage are used in routine clinical practice to predict tumor cure probability after chemo-radiotherapy, sustained efforts are made to establish more precise predictors for individual treatment. Recently chemotherapy corresponded with radiotherapy (CCR) to oral cancer has developed treatment efficiency of killing tumor cells. However we can't distinguish the number of tumor cells that may cause recurrences after radiotherapy. Then we hypothesized that hypoxic condition may have some influence of cell death by irradiation, and we tried to demonstrate how the correlation of phosphorylated H2AX (γH2AX) was influenced by oxygenation status of the tumor regions to predict radiation treatment response. Results: We used oral squamous cell carcinoma (OSCC) cell lines and divided them into two groups that showed hypoxic response or not. HSC-2 cells increased the expression level of HIF-1 alpha under hypoxia. No difference was observed in G1 arrest to irradiation of 6Gy in these cell lines. While the expression revel of γH2AX decreased in HSC-2, its revel didn't change under hypoxic condition in HSC-3 and SAS. From these findings, we postulate that one of the mechanism by which hypoxic cells become resistant to irradiation may involve the expression of HIF-1 alpha. Conclusion: The γH2AX is highly dependent on tumor cell oxygenation. Further studied are ongoing to establish the potentially important role of γH2AX under hypoxia. Citation Format: Kazuhiro Ogi, Mayumi Kawata, Takafumi Nakagaki, Kousuke Takeda, Miyazaki Akihiro, Hiratsuka Hiroyoshi. DNA double-strand breaks in hypoxic but not in normoxic conditions determine different radiosensitivity of tumors. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3846. doi:10.1158/1538-7445.AM2015-3846
Abstract 3583: Drug-resistant NPM/ALK mutants show different sensitivity to second generation tyrosine kinase inhibitors
Authors: Luca Mologni, Monica Ceccon, Diletta Fontana, Alessandra Pirola, Rocco Piazza, Carlo Gambacorti-Passerini
Journal: Cancer Research (2015)

Abstract Rearranged or mutated forms of the Anaplastic Lymphoma Kinase (ALK) are involved in the pathogenesis of various cancers, in particular anaplastic large cell lymphoma (ALCL), non-small-cell lung cancer (NSCLC) and neuroblastoma. ALK-positive tumors are currently treated with crizotinib (XalkoriTM, Pfizer) or ceritinib (ZykadiaTM, Novartis), two oral ALK inhibitors (ALKi). Additional inhibitors are in clinical trial. Despite high response rates, drug-resistant disease often develops in patients. In order to study the mechanisms that underlie resistance, we generated several ALKi-resistant cell lines in vitro. Here we present the selection of novel NPM/ALK-positive ALCL cells resistant to ASP3026 (Astellas) that grow in the presence of up to 2 μM ASP3026 and show 10 to 60 fold shift in IC50. The established ASP3026-resistant cell lines carry several point mutations in the ALK kinase domain (G1128S, C1156F, I1171N/T, F1174I, N1178H, E1210K, and C1156F/D1203N) that confer resistance to ASP3026 when reintroduced in a Ba/F3 cell model. Furthermore, the activity profile of ASP3026, crizotinib, ceritinib, alectinib, AP26113 and PF-06463922 against a panel of 20 NPM/ALK drug-resistant mutants will be presented. We report for each ALKi the IC50 value against the mutants, the IC50 fold increase over wild-type NPM/ALK (relative resistance, RR) and the IC50 ratio between parental Ba/F3 cells and mutants (therapeutic index, TI). From our screen, the G1202R and C1156F/D1203N mutations appear to be highly resistant to all tested inhibitors, therefore they are predicted to be the most challenging mutants for ALKi therapy. Citation Format: Luca Mologni, Monica Ceccon, Diletta Fontana, Alessandra Pirola, Rocco Piazza, Carlo Gambacorti-Passerini. Drug-resistant NPM/ALK mutants show different sensitivity to second generation tyrosine kinase inhibitors. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3583. doi:10.1158/1538-7445.AM2015-3583
Ki67 as a prognostic biomarker of 5-year oncologic outcomes following ablation of liver malignancies.
Authors: C. T. Sofocleous, S. K. Garg, E. N. Petre, M. Gonen, L. Petrovic, D. S. Klimstra, S. B. Solomon, K. T. Brown, R. H. Thornton, W. Alago, N. E. Kemeny
Journal: Journal of Clinical Oncology (2011)

e21160 Background: Ki67 has been used as a prognostic biomarker of oncologic outcomes after treatment of several malignant tumors. The current study assessed the long term predictive of Ki67 positive tumor cells on tissue adherent to multitined electrodes, on local tumor progression (LTP) and overall survival (OS) after radiofrequency ablation (RFA) of liver tumors. Methods: Examination of tissue adherent to electrodes after RF ablation of liver malignancies was performed looking for proliferation (Ki-67) and apoptosis (caspase-3) markers. Clinical and technical information was collected from a hepatobiliary database. In patients with tumors smaller than 5cm in diameter a retrospective review of medical records and imaging was performed. Local Tumor Progression Free Survival (LPFS) and overall survival (OS) probabilities were estimated with the Kaplan-Meier methodology and compared using the log-rank test. Multivariate analysis was performed to assess the effect of tumor size, primary pathology, and post ablation tissue characteristics on LPFS and OS. Results: Sixty-eight ablated tumors were identified in 63 patients. Post ablation tissue examinations classified 55 specimens as completely ablated/ coagulation necrosis (CN) and 13 as viable tumor (V) containing tumor cells positive for Ki-67. Mean tumor size was larger in the V (3.4 cm) than in the CN (2.5 cm) (P = .017). Ninety-two percent of patients with V and 58% with CN have died within the median follow-up of 63 months. The 1-, 3-, and 5-year LPFS and OS probabilities were significantly prolonged in the CN group (table). Conclusions: Viable tumor cells (Ki-67+) on the electrode after RFA of hepatic tumors is an independent predictor of local tumor progression free and overall survival on multivariant analysis. Survival V CN year n=13 n=55 P LPFS 1 8% 79% 3 8% 47% .001 5 8% 47% OS 1 92% 92% 3 25% 59% .032 5 8% 33%
Methylation profile of ER- and HER2-negative (ER-/HER2-) breast tumors.
Authors: M. T. Branham, D. M. Marzese, F. Gago, O. M. Tello, J. I. Orozco, L. M. Vargas-Roig, M. Roqué
Journal: Journal of Clinical Oncology (2011)

e21098 Background: Breast cancer is a group of clinically, histopathologically and molecularly heterogeneous diseases, with diverse outcomes and responses to treatment. ER-/HER2- is an immunohistochemical description of breast cancers with a double negative staining for ER and HER2. These tumors have an aggressive clinical behavior and poor prognosis. The hypermethylation of CpG islands (CpGI) is a common epigenetic alteration for suppressing gene expression in breast cancer. Understanding how these epigenetic changes are involved in tumor progression is important for a better comprehension of tumor biology. Here we evaluated the methylation status of ER-/HER2- compared to luminal breast tumors. Methods: For the methylation analysis, we used the methyl specific-multiplex ligation probe amplification assay. Seventy invasive ductal carcinomas (IDC) were included in the study. In 20 IDCs we analyzed 127 CpGI and in 50 IDCs we analyzed 49 CpGI. Results: Among the islands studied we found positive association between ER-/HER2- tumors and methylated MGMT (p<0.002) and CD44 (p<0.01) and non methylated GSTP1 (p<0.04), PAX6 (p<0.04), MSH2 (p<0.002), MSH3 (p<0.001) and CACNA1A (p<0.049) genes. Conclusions: ER-/HER2- cancers present a clearly different methylation profile, compared to luminal tumors. These results could add knowledge to the behavior of these tumors and improve future treatment options.
Abstract B25: Activation of Wnt/β-catenin signaling pathway enhances pancreatic cancer development and the malignant potential via up-regulation of Cyr61/CCN1
Authors: Makoto Sano, David R. Driscoll, Wilfredo E. DeJesus-Monge, Brian Quattrochi, Victoria A. Appleman, Jianhong Ou, Lihua Julie Zhu, Nao Yoshida, Shintaro Yamazaki, Tadatoshi Takayama, Masahiko Sugitani, Norimichi Nemoto, David S. Klimstra, Brian C. Lewis
Journal: Cancer Research (2016)

Abstract Pancreatic ductal adenocarcinoma (PDAC), a poor prognostic cancer, commonly develops following activating mutations in the KRAS oncogene. Activation of the Wnt signaling pathway is also commonly observed in PDAC. To ascertain the impact of postnatal activation of the Wnt signaling pathway in PDAC development, we combined the elastase-tva-based RCAS-TVA pancreatic cancer model with the established LSL-KrasG12D, Ptf1a-cre model. Delivery of RCAS viruses encoding β-cateninS37A and Wnt1 stimulated the progression of premalignant PanIN and PDAC development. Indeed, mice injected with RCAS-β-cateninS37A and Wnt1 had reduced survival relative to RCAS-GFP controls (P &amp;lt; 0.05). Active β-catenin or its DNA-binding partner TCF4 enhanced PDAC cell proliferation, soft-agar colony formation, as well as migration and invasion activity. In contrast, these phenotypes were significantly blocked by the introduction of Icat, an inhibitor of the β-catenin/TCF4 interaction. Meanwhile, we identified Cyr61/CCN1 as a target molecule for Wnt/β-catenin signaling pathway in PDAC. Nuclear β-catenin and Cyr61/CCN1 expression were predominantly detected in moderately to poorly differentiated murine and human PDAC. Indeed, nuclear β-catenin and Cyr61/CCN1-positivity independently correlated with poor prognosis (P &amp;lt; 0.01). Knockdown of Cyr61/CCN1 in a β-catenin-activated PDAC cell line reduced soft agar, migration and invasion activity. Together, these data suggest that the Wnt/β-catenin signaling pathway enhances pancreatic cancer development and malignancy in part via up-regulation of Cyr61/CCN1. Citation Format: Makoto Sano, David R. Driscoll, Wilfredo E. DeJesus-Monge, Brian Quattrochi, Victoria A. Appleman, Jianhong Ou, Lihua Julie Zhu, Nao Yoshida, Shintaro Yamazaki, Tadatoshi Takayama, Masahiko Sugitani, Norimichi Nemoto, David S. Klimstra, Brian C. Lewis.{Authors}. Activation of Wnt/β-catenin signaling pathway enhances pancreatic cancer development and the malignant potential via up-regulation of Cyr61/CCN1. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2016 May 12-15; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(24 Suppl):Abstract nr B25.
Contribution of PET/CT In the Design of the Involved Node Radiotherapy (INRT) Concept for Patients with Localized Hodgkin Lymphoma: Preliminary Results on 117 Patients.
Authors: Vincent Ribrag, Véronique Edeline, Alijosa Celebic, Christophe Fermé, Claude Ruelle, Bérénice Boulet, Théodore Girinsky, Anne Auperin
Journal: Blood (2010)