bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4658: Use of a defined oleander extract by advanced cancer patients: Case reports on toxicity and tumor-related outcomes
Authors: Block Keith I. , Gyllenhaal Charlotte , Newman Robert A. 
Published: May 2015

Abstract
The present study reports cases of advanced cancer patient taking an extract of Nerium oleander now in Phase 1 clinical trials in cancer patients. A phytochemical constituent of the extract, oleandrin, has multiple anticancer activities including inhibition of NF-kappaB and induction of apoptosis. We present case reports of 9 metastatic cancer patients who received the extract on personal use exemptions. Five of the patients also received full integrative programs at an integrative medicine center. Cases included 4 colon cancer patients, 3 pancreatic cancer patients (1 neuroendocrine and 2 adenocarcinoma), 1 renal cell carcinoma and 1 lung cancer patient. For the patients at the integrative center, all of whom took the extract during periods when they were receiving chemotherapy, toxicity grading of chemotherapy side effects was performed. We analyzed the case records for potential effects of the extract on tumor regression/stability in the absence of chemotherapy, survival time, use concurrent with chemotherapy and toxicity. The renal cell patient experienced tumor regression for 12 months with the extract alone; the 3 pancreatic cancer patients and a colon cancer patient experienced disease stabilization. Survival times were extended for all patients with survival times ranging from 32 months to 11 years for these patients with metastatic disease. Chemotherapy was well tolerated by colon cancer patients with only grade 1-2 toxicity during as many as 70 cycles of chemotherapy. Mild toxicities thought to be related to the extract included lightheadedness and mild tingling and burning of the mouth with use of the sublingual preparation. Severe toxicities including one myocardial infarction and one deep-vein thrombosis were observed but not suspected to be related to the extract. Good clinical outcomes and low toxicity were thus observed for the extract in these patients.
Citation Format: Keith I. Block, Charlotte Gyllenhaal, Robert A. Newman. Use of a defined oleander extract by advanced cancer patients: Case reports on toxicity and tumor-related outcomes. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4658. doi:10.1158/1538-7445.AM2014-4658
Abstract 466: LMO1 is a novel oncogene in neuroendocrine lung cancer
Authors: Zhao Zhenze , Ma Xiuye , Yu Xiaojie , Hsiao Tzu-Hung , Chen Yidong , Suraokar Milind , Wistuba Ignacio , Minna John D. , Pertsemlidis Alexander , Du Liqin 
Published: May 2015

Abstract
Introduction. The aim of the study is to characterize the role of LMO1 in tumorigenesis of neuroendocrine lung cancer. LMO1 is a transcription factor that belongs to the LMO protein family containing the cysteine-rich LIM domains. LMO1 has been demonstrated to function as an important oncogene in the development of T-lineage leukemia and lymphoma. A recent study in neuroblastoma suggests that aberrant overexpression of LMO1 may play a critical role in the development of neuroendocrine cancers. The role of LMO1 in neuroendocrine lung cancer, however, was not investigated.
Experimental Approaches. By analyzing a large panel of cell lines including lung cancer cell lines and normal lung epithelial cells, we compared the relative expression of LMO1 in different subtypes of lung cancers, and examined the correlation of LMO1 expression levels with neuroendocrine differentiation markers. Using in vitro approaches, we investigated the function of LMO1 in regulating lung cancer cell growth. To investigate the clinical significance of LMO1 dysregulation in lung cancer patients, we analyzed the correlation of LMO1 tumor levels with lung cancer patient survival.
Results. We show that LMO1 is significantly overexpressed in small cell lung cancer (SCLC), an aggressive and major subtype of neuroendocrine lung cancers, relative to non-small cell lung cancer (NSCLC) and normal lung cells. In addition, in NSCLC cells, LMO1 mRNA levels are significantly correlated with expression of neuroendocrine differentiation markers. Functional in vitro investigations indicate that LMO1 overexpression significantly promotes growth of cultured lung cancer cells, suggesting its oncogenic function in lung cancer. More strikingly, our investigations of two independent lung cancer patient populations indicate that high tumor LMO1 mRNA level is an independent predictor of poor patient survival.
Conclusions. Altogether, our findings strongly suggest that LMO1 is a neuroendocrine-specific oncogene in lung cancer that plays an important role in determining the cancer aggressiveness. Further studies are certainly warranted to define the mechanisms underlying the oncogenic function of LMO1 in neuroendocrine lung cancer and to further evaluate the clinical significance of LMO1 as a diagnostic and prognostic marker for neuroendocrine lung cancers in prospective studies.
Citation Format: Zhenze Zhao, Xiuye Ma, Xiaojie Yu, Tzu-Hung Hsiao, Yidong Chen, Milind Suraokar, Ignacio Wistuba, John D. Minna, Alexander Pertsemlidis, Liqin Du. LMO1 is a novel oncogene in neuroendocrine lung cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 466. doi:10.1158/1538-7445.AM2014-466
Abstract 4663: KRAS, BRAF, and EGFR mutational analysis in ovarian, colon, and lung cancers by highly multiplex PCR/barcoded-magnetic-bead (BMB) suspension-array assays
Authors: Lei Jason , Hsu Julia , Jen Peggy , Huang Daniel , Chung Andre , Kao Lloyd , Chang Miller , Yuan Chiou-Chung , Lee Wei-Hwa , Yeh Chi-Tai , Tsao Dean 
Published: May 2015

Abstract
Anti-epithelial growth factor receptor (EGFR) monoclonal antibodies and small molecule EGFR inhibitors have been used for treating metastatic colorectal cancer (mCRC) and non-small cell lung cancer (NSCLC), respectively. However, since a relatively large proportion of the mCRC and NSCLC patients carry the activating KRAS/BRAF mutations that can render these EGFR-targeted therapies ineffective, the KRAS/BRAF mutation testing is now required for such prescription. In contrast, epithelial ovarian cancer (EOC) thus far has been treated by surgery, radiotherapy, and/or chemotherapy depending on the tumor stages. However, it has been shown that a high percentage of tumors of the mucinous, endometrioid, low-grade serous, and other types of EOC patients also contain KRAS or BRAF somatic mutations, suggesting that drugs targeting the mediators of the EGFR pathway may have implications on treating EOC of certain types. The conventional analysis of the KRAS, BRAF, and EGFR mutations has been done by multiple reactions with one mutation target per reaction, thus requiring a large amount of precious patient sample for complete testing. Here we present three highly multiplex molecular diagnostic assays, utilizing amplification by allele-specific PCR and automatic detection by a platform designed around the barcoded-magnetic-bead (BMB) suspension-array technology, for detection of 12 KRAS (in codons 12 and 13), six BRAF (in codon 600), and 21 EGFR (in exons 18-21) mutations in mCRC, NSCLC, and EOC patient samples. The results indicate that, albeit all the reaction components are in single wells, these highly multiplex PCR/BMB assays, by comparing with the sequencing results, not only are sensitive and specific but also can conserve precious tissue specimens, save operating time and labor, reduce turnaround time, and increase assay throughput.
Citation Format: Jason Lei, Julia Hsu, Peggy Jen, Daniel Huang, Andre Chung, Lloyd Kao, Miller Chang, Chiou-Chung Yuan, Wei-Hwa Lee, Chi-Tai Yeh, Dean Tsao. KRAS, BRAF, and EGFR mutational analysis in ovarian, colon, and lung cancers by highly multiplex PCR/barcoded-magnetic-bead (BMB) suspension-array assays. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4663. doi:10.1158/1538-7445.AM2014-4663
Abstract 4667: The impact of IASLC/ATS/ERS classification of lung adenocarcinoma on survival after recurrence in resected adenocarcinoma
Authors: Hung Jung-Jyh , Chou Teh-Ying , Hsu Wen-Hu , Wu Yu-Chung 
Published: May 2015

Abstract
Objective: Factors predicting post-recurrence survival (PRS) in lung adenocarcinoma have not been reported. This study aimed to investigate the prognostic factors of PRS, including the new classification of lung adenocarcinoma proposed by the International Association for the Study of Lung Cancer (IASLC), the American Thoracic Society (ATS), and the European Respiratory Society (ERS), in resected lung adenocarcinoma after recurrence.
Methods: The clinicopathological characteristics of 140 patients with recurrence after complete resection of lung adenocarcinoma at Taipei Veterans General Hospital were retrospectively reviewed. The prognostic factors of PRS were analyzed.
Results: The pattern of recurrence included local only in 22 (17.1%), distant only in 40 (31.0%), and both local and distant in 84 (51.9%) of patients. The 2- and 4-year PRS were 67.2% and 39.1%, respectively. The most common organ sites of metastasis were the contralateral lung (40.7%), followed by the brain (37.1%) and bone (30.7%). Univariate analysis showed that N2 status (vs. N0 and N1) (P = 0.007), stage III (vs. stage I and II) (P = 0.043), micropapillary/solid predominant pattern group (P = 0.012), liver metastasis (P = 0.033), and no treatment for recurrence (P &lt; 0.001) were significant predictors of worse PRS. Multivariate analysis revealed that N2 status (P = 0.036), micropapillary/solid predominant pattern group (P = 0.018), and no treatment for recurrence (P &lt; 0.001) were still significant predictors of worse PRS.
Conclusions: N2 status, micropapillary/solid predominant pattern group, and no treatment for recurrence predict worse PRS in patients with resected lung adenocarcinoma. The new classification of lung adenocarcinoma had significant impact on PRS.
Citation Format: Jung-Jyh Hung, Teh-Ying Chou, Wen-Hu Hsu, Yu-Chung Wu. The impact of IASLC/ATS/ERS classification of lung adenocarcinoma on survival after recurrence in resected adenocarcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4667. doi:10.1158/1538-7445.AM2014-4667
Abstract 4668: A next generation sequencing assay to detect the fusion products of ALK, ROS1 and RET with any fusion partner genes and hotspot mutations in FFPE samples
Authors: Xu Qiang , Wang Guan , Li Bo , Qian Maoxiang , Fang Douglas , Sun Lele , Chen Yundi , Sun Hongye 
Published: May 2015

Abstract
Targeted drugs have been widely used in the treatment of lung cancer, especially for non small cell lung cancer (NSCLC) patients. NCCN guideline lists multiple drugs which are particularly effective in the subgroup of patients with specific gene mutation variants, including the fusion transcripts of ALK, ROS1 and RET, and the mutations of EGFR, KRAS, BRAF and HER2. Multiple techniques have been developed to detect fusion transcripts in tumor samples, such as FISH, IHC and PCR assays. FISH is the most accurate method for fusion detection currently. The split probe FISH assay, which does not require the pre-knowledge of what is the fusion partner with ALK for example, can detect unknown ALK fusion products as well. However, it fails to identify which gene is fused with ALK (or other oncogene) in the chimera products, therefore is not informative for the mechanism or drug resistance study. In addition, due to the limitation on the fluoresce dye, it is quite difficult to multiplex fusion FISH probes for different genes into one assay.
We describe here a next generation sequencing assay to detect a panel of fusion transcripts and mutations in one single assay. Our single assay can detect the fusion products of ALK, ROS1 and RET with any known or unknown fusion partners, together with the hotspot mutations in EGFR, KRAS, BRAF and HER2. Our assay can identify not only the exact sequence of the unknown fusion partners, but also any mutations within the full coding regions of ALK, ROS1 and RET. This information is critical for the resistance mechanism study and the next generation inhibitor drug development, since about half of the ALK inhibitor resistance was caused by the mutations in ALK gene itself. We have identified a novel ALK fusion gene with a never-reported fusion partner in a lung cancer patient. The xenograft model derived from this patient responds to crizotinib well in the in vivo study (published on Journal of Thoracic Oncology). We have demonstrated that our assay can reliably detect both the novel fusion and the well known EML4-ALK fusion from only 1-2 5um FFPE slides of the lung tumor tissues, together with other possible fusions and mutations as well.
Note: This abstract was not presented at the meeting.
Citation Format: Qiang Xu, Guan Wang, Bo Li, Maoxiang Qian, Douglas Fang, Lele Sun, Yundi Chen, Hongye Sun. A next generation sequencing assay to detect the fusion products of ALK, ROS1 and RET with any fusion partner genes and hotspot mutations in FFPE samples. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4668. doi:10.1158/1538-7445.AM2014-4668
Abstract 4669: Prevalence of high risk human papillomavirus infection in different cervical cytological features among health examination of women in National Cancer Institute, Thailand
Authors: Sangrajrang Suleeporn , Laowahutanont Piyawat , Kalalak Anant , Jamsri Paphawin 
Published: May 2015

Abstract
High-risk (HR) human paillomavirus (HPV) testing is important in cervical cancer screening for triage colposcopy. The objective of the study was to evaluate the prevalence of HPV HR infection in different cytological features among health examination women. DNA was extracted from 2896 residual liquid-based cytology specimens collected during routine liquid-based Papanicolaou tests at National Cancer Institute. Overall, HPV HR prevalence was 9.3% including 1.6% of HPV-16 and 0.4% of HPV-18. HPV prevalent was highest in women younger than 35 years of age, decreasing in women of older age. Among women with normal cytology, HPV HR positive were found in 6.7%. In abnormal cytology, HPV HR were found in 46.7% atypical squamous cells (ASC), 54.8% were low-grade squamous intraepithelial lesions (LSIL) and 80.0% were high-grade squamous intraepithelial lesions (HSIL). HPV-16 were detected in 8.6%, 6.5% and 12.0% of ASC, LSIL and HSIL, respectively.The results of this study provide baseline information on the HPV type distribution, which may useful for clinicians to decide who should be monitored or treated more aggressively.
Note: This abstract was not presented at the meeting.
Citation Format: Suleeporn Sangrajrang, Piyawat Laowahutanont, Anant Kalalak, Paphawin Jamsri. Prevalence of high risk human papillomavirus infection in different cervical cytological features among health examination of women in National Cancer Institute, Thailand. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4669. doi:10.1158/1538-7445.AM2014-4669
Abstract 4673: ARID1A expression and its relation with microsatellite instability and clinicopathological characteristics in colorectal and gastric cancers of Korean patients
Authors: Lee Soo Young , Kim Duck-Woo , Lee Hye Seung , Ihn Myong Hoon , Oh Heung-Kwon , Kang Sung-Bum 
Published: May 2015

Abstract
AT-rich interactive domain-containing protein 1A (ARID1A) is a subunit of the SWI-SNF chromatin-remodeling complex, which is considered to perform a tumor suppressor function. Somatic mutations of ARID1A were reported to be detected in about 50% of colorectal cancer (CRC), but loss of expression seems vary according to tissue type and microsatellite instability (MSI) status. So, we designed this study to identify the frequency of loss of ARID1A expression and its clinical relevance in CRC and gastric cancer (GC) of Korean patients. Immunohistochemistry for ARID1A was performed using tissue microarray blocks containing 197 CRCs and 275 SCs, and paired normal mucosa. Data on MSI status were available in 178 of 197 CRCs and 233 of 275 GCs. Clinicopathological data of the patients were collected and analyzed. We identified 12 (12/197, 6.1%) CRCs showing loss of ARID1A expression, all of which were microsatellite stable. In 178 CRCs with identified MSI status, 3 (1.7%) MSI-H and 6 (3.4%) MSI-L tumors showed normal expression of ARID1A, contrary to MSS tumors (ARID1A loss: 10/169, 5.9%). Among GCs, 8.0% (22/275) showed loss of ARID1A expression and 6.4% (15/233) were MSI-H. Tumors with loss of ARID1A expression accounted for 13.3% (2/13) of GCs with MSI-H whereas 5.0% (11/207) of GCs with MSS. However, there was no association between ARID1A expression and MSI status in both CRCs (p=0.754) and SCs (p=0.200). Expression of ARID1A in paired normal mucosal epithelial cells was normal in all patients. Clinicopathological factors were not associated with ARID1A expression in both cancers except that CRCs with loss of ARID1A expression showed less frequent lymphatic invasion than those with normal expression (25.0% vs. 69.0%, p=0.003). There was no association between ARID1A expression and 3-year disease-free survival or 5-year overall survival in both cancers. In this study population, loss of ARID1A expression was uncommon and not relevant to MSI-H tumors. Its clinical implication for the prognosis of CRC and GC patients seems to need further studies with more accumulated data.
Citation Format: Soo Young Lee, Duck-Woo Kim, Hye Seung Lee, Myong Hoon Ihn, Heung-Kwon Oh, Sung-Bum Kang. ARID1A expression and its relation with microsatellite instability and clinicopathological characteristics in colorectal and gastric cancers of Korean patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4673. doi:10.1158/1538-7445.AM2014-4673
Abstract 4676: In-vitro adenosine triphosphate-based chemotherapy response assay (ATP-CRA) results comparison between primary and recurrent gynecologic cancer using a unique cohort
Authors: Nam Eun J. , Kim Young Tae , Kim Sang Wun , Kim Sunghoon , Yim Ga Won 
Published: May 2015

Abstract
Purpose: The standard chemotherapy regimen in gynecologic cancer treatment is not established, particularly in cases of recurrence. The objective of this study is to evaluate the role of in vitro adenosine triphosphate-based chemotherapy response assay (ATP-CRA) in recurrent gynecologic cancer.
Methods: We examined 20 matched primary and recurrent tumor pairs of each patient with recurrent gynecologic cancer, using ATP-CRA. Tumor samples were obtained from primary and secondary debulking or palliative surgery. Inhibition rates of the chemotherapeutic agents were compared.
Results: The diseases of patients analyzed in this study were composed of ovarian/peritoneal cancer [11 patients (55%)], uterine cancer [7 patients (35%)], and cervical cancer [3 patients (15%)]. The average of inhibition rate was 36.3% in samples obtained from primary surgery and 33.6% in samples from secondary debulking or palliative surgery (P&gt;0.1). In the primary surgery cases, the drugs showing high inhibition rate were ifosfamide (56.4%), cisplatin (52.6%), and irinotecan (43.3%) in the following order, and in the secondary operation cases, ifosfamide (54.3%), cisplatin (44.3%), and Topotecan (39.9%). The number of cases in which the ATP-CRA result had actual influence in choosing the regimen, were 0 (0%) in primary surgery cases, and 7 (35%) in secondary surgery cases (P&lt;0.05).
Conclusion: The drug inhibition rate did not decrease in the recurrent tumors compared to the primary tumors. The actual influence of ATP-CRA results increase significantly in the secondary surgery compared to the primary one.
Note: This abstract was not presented at the meeting.
Citation Format: Eun Ji Nam, Young Tae Kim, Sang Wun Kim, Sunghoon Kim, Ga Won Yim. In-vitro adenosine triphosphate-based chemotherapy response assay (ATP-CRA) results comparison between primary and recurrent gynecologic cancer using a unique cohort. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4676. doi:10.1158/1538-7445.AM2014-4676
Abstract 4681: The use of patient derived malignant effusions as in vitro models for a personalized healthcare-approach in anticancer therapy
Authors: Ruiz Christian , Vlajnic Tatjana , Arabi Leila , Wyttenbach Sina , Baschiera Betty , Rothschild Sacha , Kustermann Stefan , Zippelius Alfred , Roth Adrian , Bubendorf Lukas 
Published: May 2015

Abstract
Background
The use of patients' own cancer cells for in vitro selection of the most promising treatment is an attractive concept in personalized medicine. Human carcinoma cells from malignant effusions (MEs) are well suited for this purpose since they have already adapted to the liquid environment in the patient and are not enclosed by stromal cell compartments. Aim of this study was the establishment of a consistent approach for the in-vitro ex-vivo culture of MEs and the comprehensive analysis of the effect of chemotherapeutic as well as targeted drugs.
Methods
MEs from patients with lung or breast cancer were selected for this study. After morphological and molecular characterization, epithelial cells were cultured in cell culture medium supplemented with 30% of patient derived sterile filtered effusion supernatant. Growth characteristics were monitored in real-time using the xCelligence system. MEs were treated with targeted therapeutics according to their genomic profile or with chemotherapeutics based on the recommendation by the oncologist.
Results
We have developed a reliable system for the ex-vivo culture of MEs and the application of drug tests in-vitro. The use of an enrichment system for epithelial cells allowed for culturing of effusions with only moderate tumor cell content. Experiments using drugs revealed dose-dependent effects and specific growth inhibitory effects of targeted therapeutics, such as Crizotinib and Erlotinib.
Conclusions
In this study, we show that cancer cells from patient derived MEs can be cultured and treated in-vitro. Based on our developed setup, these MEs can be genomically characterized by whole genome approaches in order to identify genomic vulnerabilities and then subjected to growth tests by using the respective targeted drugs. This approach could be an important step towards personalized healthcare, at least for patients with malignant effusions.
Citation Format: Christian Ruiz, Tatjana Vlajnic, Leila Arabi, Sina Wyttenbach, Betty Baschiera, Sacha Rothschild, Stefan Kustermann, Alfred Zippelius, Adrian Roth, Lukas Bubendorf. The use of patient derived malignant effusions as in vitro models for a personalized healthcare-approach in anticancer therapy. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4681. doi:10.1158/1538-7445.AM2014-4681