bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4864: Targeted melanoma therapies as radiosensitizers
Authors: Smith Jessica L. , Chang Cecilia , Wang Tim , Rizos Helen , Shen Han , Carlino Matteo , Hau Eric 
Published: August 2019

Abstract
Introduction: In BRAFV600 mutant melanoma combination of BRAF and MEK inhibitors is associated with a rapid response in approximately 70% of patients, and an improvement in survival. Radiotherapy is used in the treatment of melanoma in multiple clinical settings including stereotactic radiosurgery for brain metastasis, oligo-metastatic extracranial disease and palliative radiotherapy to symptomatic lesions. Preclinical studies, and a small number of clinical case reports suggest the BRAF inhibitor vemurafenib and the MEK inhibitor trametinib leads to increased radiosensitivity.
Aims: To determine if BRAF Inhibitors dabrafenib, vemurafenib and encorafenib, alone or in combination with their corresponding MEK Inhibitors, are radiation-sensitising in BRAF-mutant treatment naive melanoma cells.
Methods: Three melanoma cell lines harbouring a BRAF V600E mutation were studied: A375, SkMel28 and MM200. The half-maximal inhibitory concentration (IC50) for each cell line was determined by MTS assays for vemurafenib, dabrafenib, encorafenib, and the MEK inhibitors trametinib, binimetinib and cobimetinib. Clonogenic assays were conducted on each cell line. The optimal dose of BRAF and MEK inhibitors was determined from MTS assay and single drug clonogenic assays. Cells were treated with BRAF or MEK inhibitor alone and in combination. Cells were also treated with increasing doses of radiation (X-RAD 320 irradiator, PXI). The mode of cell death and changes in cell morphology were determined by live cell imaging (Wide Field Live Cell Observer, Ziess) for five days following the above treatments.
Results:Using Clonogenic assays, we confirmed that radiation sensitivity varies across different melanoma cell lines, with MM200 being significantly more sensitive to radiation then SKMel28. Clonogenic assays demonstrated that vemurafenib, dabrafenib, encorafenib, trametinib and binimetinib increased radiosensitivity across all three-cell lines. Further, the level of radiosensitsation was greater in combination across all three sets, than with either BRAF or MEK inhibitor alone. Using live cell imaging, we were able to confirm this increase in cell death, and visualise differences in the mode of cell death and morphology with these therapies.
Conclusions: Vemurafenib, dabrafenib, encorafenib, trametinib and binimetinib were shown in this study to be radiosensitisers in BRAFV600Emutant melanoma cell lines. Radiosensitisation was greatest with combined BRAF and MEK inhibition. Further studies are being conducted to determine if this sensitisation continues after BRAF resistance develops.
Citation Format: Jessica L. Smith, Cecilia Chang, Tim Wang, Helen Rizos, Han Shen, Matteo Carlino, Eric Hau. Targeted melanoma therapies as radiosensitizers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4864.
Abstract 4867: Radiosurgery consultation to treatment interval, additional brain metastases during the interim and outcomes after therapy
Authors: Ampil Federico , Caldito Gloria , Richards Troy 
Published: August 2019

Abstract
Background: Expediting the process of diagnosis and treatment should theoretically improve outcome. Delays in beginning therapy can cause anxiety to the patients and physicians who may be concerned about tumor progression before treatment is initiated. Treatment delays can be characterized as patient-generated or logistical medical infrastructure prolongations.
Objective: The goal of the present study was to determine the impact of stereotactic radiosurgery (RS) consultation to treatment interval (CTI) and the development of additional brain metastases (BRM) during the interim on outcomes after RS.
Methods: Between October 2014 and April 2018, 15 individuals developed more contrast-enhancing BRMs during the CTI. These patients were treated with gamma knife RS (including the six patients who underwent gross resection of metastatic intracranial neoplasm). The median duration of CTI was 19 days (range 5-61 days). A comparison of the ≤19 days CTI (eight patients) to the &gt;19 days CTI (seven patients) was performed to assess the effects of the extent of delay to RS. The total number of BRM for RS was 68. The median target volume was 0.48 cm3, and the median margin dose was 24 Gy.
Results: Most (67%) of the subjects exhibited good performance status. The overall crude survival rate at two years was 27%; acute or late toxicity after RS was not observed. Comparison of the CTI groups revealed: i) A longer CTI was not associated with a poorer prognosis; ii) BRM recurrence after RS was less common in this patient subgroup; iii) Quality of life (QOL) was satisfactory even though the CTI was prolonged.
Conclusion: Acceptable longevity with minimal morbidity satisfying the QOL consideration was found in this audit of cases about CTI and the occurrence of more BRMs during the interim. Decreasing CTI in patients with BRM remains an important goal of quality improvement.
Citation Format: Federico Ampil, Gloria Caldito, Troy Richards. Radiosurgery consultation to treatment interval, additional brain metastases during the interim and outcomes after therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4867.
Abstract 4872: Disulfiam, a re-positioned aldehyde dehydrogenase inhibitor, enhances radiosensitivity of human glioblastoma cells in vitro
Authors: Koh Hyeon Kang , Seo Soo Yeon , Kim Jin Ho , Kim Hak Jae , Chie Eui Kyu , Kim Seung-Ki , Kim Il Han 
Published: August 2019

Abstract
Purpose : Glioblastoma, the most common brain tumor in adults, has poor prognosis. The purpose of this study was to determine the effect of disulfiram (DSF), an aldehyde dehydrogenase inhibitor, on in vitro radiosensitivity of glioblastoma cells with different methylation status of O6-methylguanine-DNA methyltransferase (MGMT) promoter and the underlying mechanism of such effect.
Materials and Methods : Five human glioblastoma cells (U138MG, T98G, U251MG, U87MG, and U373MG) and one normal human astrocyte (NHA) cell were cultured and treated with DSF or 6MV x-rays (0, 2, 4, 6, 8 Gy). For combined treatment, cells were treated with DSF before irradiation. Surviving fractions fit from cell survival based on colony forming ability. Apoptosis, DNA damage repair, and cell cycle distribution were assayed by Western blot for cleaved caspase-3, γH2AX staining, and flow cytometry, respectively.
Results : DSF induced radiosensitization in most of the glioblastoma cells, especially, in the cells with radioresistance as wildtype unmethylated promoter (MGMT-wt), but did not in normal NHA cell. DSF augmented or induced cleavage of caspase-3 in all cells after irradiation. DSF inhibited repair of radiation-induced DNA damage in MGMT-wt cells, but not in cells with methylated MGMT promoter (MGMT-meth). DSF abrogated radiation-induced G2/M arrest in T98G and U251MG cells.
Conclusion : Radiosensitivity of glioblastoma cells were preferentially enhanced by pre-irradiation DSF treatment compared to normal cell, especially radioresistant cells such as MGMT-wt cells. Induction of apoptosis or inhibition of DNA damage repair may underlie DSF-induced radiosensitization. Clinical benefit of combining DSF with radiotherapy should be investigated in the future.
Citation Format: Hyeon Kang Koh, Soo Yeon Seo, Jin Ho Kim, Hak Jae Kim, Eui Kyu Chie, Seung-Ki Kim, Il Han Kim. Disulfiam, a re-positioned aldehyde dehydrogenase inhibitor, enhances radiosensitivity of human glioblastoma cells in vitro [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4872.
Abstract 4874: Incidental gallbladder cancer: Best step forward
Authors: Galodha Saurabh , Mahajan Puneet 
Published: August 2019

Abstract
Objective: There is a rising trend of Incidental Gall Bladder Cancer (IGBC) with increase in laparoscopic cholecystectomy. Objective of our study was to evaluate the efficacy of further management (completion surgery and adjuvant chemotherapy) in IGBC in terms of long-term survival (&gt; 5 years).
Material and Method: Clinic-pathological and survival data of 145 IGBC patients was analysed from a prospectively maintained database of GBC. Patients investigated with triple phase CT abdomen and if required PET-CT. Diagnostic laparoscopy with Completion extended cholecystectomy performed in patients amenable for resection. Adjuvant therapy consisted of gemcitabine and cisplatin. Patients followed up with OPD visits and telephonic enquiry.
Results: 864 patients of GBC were treated during the period of January 1989 to December 2012. Out of these 145 patients were IGBC [113 women (77%), median age; 52 years)]. 96 patients were detected on histopathology while 49 were diagnosed intra-operatively. Open cholecystectomy was done in 88, laparoscopic in 45 while 12 underwent laparoscopic converted to open cholecystectomy. Commonest T stage was T3 (n=71). All patients were re-evaluated after diagnosis of IGBC. 80 patients (55%) were taken up for surgery of which, 50 (62.5%) underwent completion extended cholecystectomy (rest had metastases or locally advanced unresectable disease). Median time interval between index surgeries to re-exploration was 35 days (0-250). It was longer in patients who could not undergo completion extended cholecystectomy (70 days vs. 49 days). Overall 5-year survival in pT1b, pT2 and pT3 stage was 49.5%, 36.1% and 8.4% respectively, but was considerably better in patients who underwent completion extended cholecystectomy compared with those who did not undergo re-surgery [pT1; 62.5% vs. 29.1%, pT2; 52.2% vs. 15.9%, pT3; 22.6% vs. 7.2%, p&lt;0.001]. Prognostic factors associated with poor prognosis were higher T stage, R1 resection, bile spillage during index surgery, no completion surgery and residual disease on re-exploration on univariate analysis. On multivariate analysis factors portending poor prognosis were higher T stage, R1 resection and residual disease.
Conclusion: Early recognition, early completion radical surgery and adjuvant therapy lends considerable survival benefit to patients of incidental carcinoma gall bladder. Residual disease and R1 resection portends a poorer survival. High index of suspicion should be kept in patients with thick walled GB to avoid missing a malignancy at index surgery.
Citation Format: Saurabh Galodha, Puneet Mahajan. Incidental gallbladder cancer: Best step forward [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4874.
Abstract 4876: Clinical significance of diffuse-type histological type coexistence in Stage II/III gastric cancer
Authors: Tanaka Hiroaki , Muguruma Kazuya , Tamura Tatsuro , Toyokawa Takahiro , Shibutani Masatsune , Fukuoka Tatsunari , Nagahara HIsashi , Ohira Masaichi 
Published: August 2019

Abstract
Background: Signet ring cell carcinoma (sig) and non-solid poorly differentiated adenocarcinoma (por2) are the histological forms of gastric cancer called diffuse type. They are considered to be a tissue type with a poor prognosis. Adjuvant chemotherapy using S-1 is standard therapy for stage II/III gastric cancer in Japan, however, clinical relevance of histological type to outcome of adjuvant therapy remains unclear.
Purpose: The purpose of the present study was to examine the impact of the coexistence of diffuse type on the prognosis of stage II/III gastric cancer.
Patients and Methods: We retrospectively analyzed the clinicopathologic data of 935 gastric carcinoma patients who underwent gastrectomy between 2007 and 2015 at our department.
Results: We observed that there were 62 cases (17%) with sig mixed (dominant 12 cases, inferiority 50 cases) and 104 cases (30%) with por 2 mixed (dominant 19 cases, inferiority 85 cases). The patients with por2 or sig had more peritoneum dissemination compared with intestinal types. In Stage III, the recurrence rate was high in the case with sig mixed, the 3-year relapse-free survival rate was 36% in the mixed case and 55% in the non-mixed case. However, we found no correlation of sig mixture to prognosis of patients with Stage II. Among the patient who received the S-1 adjuvant chemotherapy, the prognosis of sig mixture was relatively poor.
Conclusion: In the case of stage III gastric cancer in which there was mixed signet ring cell carcinoma in the tissue, the recurrence rate was high and the prognosis was poor. Our findings suggested that it should be needed to treat sig mixed cases as a high risk group in the future postoperative adjuvant chemotherapy for gastric cancer.
Citation Format: Hiroaki Tanaka, Kazuya Muguruma, Tatsuro Tamura, Takahiro Toyokawa, Masatsune Shibutani, Tatsunari Fukuoka, HIsashi Nagahara, Masaichi Ohira. Clinical significance of diffuse-type histological type coexistence in Stage II/III gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4876.
Abstract 4882: Expression atlas of FGF and FGFR genes in pan-cancer uncovered predictive biomarkers for FGFR inhibition response in clinical trials
Authors: Li Yuan , Wu Long , Cheng Yanlei , Tao Weiping , Wu Dawei , Ma Fei , Li Ning 
Published: August 2019

Abstract
Genomic variation of FGFR has been intensively investigated in cancer for years, however, clinical trials on the basis of FGFR mutation or amplification as a druggable target of FGFR inhibitors have produced disappointing clinical outcomes. Therefore, the identification of predictive biomarkers for FGFR-targeted agents has remained a crucial issue. Expression profiles of FGF and FGFR in 8,111 patients with 24 types of solid tumors and 879 tumor cell lines along with drug sensitivity data were obtained from public databases. Differential expression, survival and correlation analyses were performed to uncover the clinical relevance of FGF and FGFR genes expression in pan-cancer. As results, FGF and FGFR were frequently dysregulated in pan-cancer. Moreover, almost all the FGF and FGFR were significantly associated with overall survival in at least two cancer types, however, mixed prognostic values were seen in pan-cancer. More importantly, tumor cell lines with high FGFR1/3 expression were more sensitive to FGFR inhibitor PD173074, especially in breast cancer, liver cancer, lung squamous cell carcinoma and ovarian cancer. The predicted positive ratios of FGFR1/2/3/4 were generally over 10% in most tumor types, especially in squamous cell carcinoma. High positive FGFR1 or 3 expression ratio were predicted in cholangiocarcinoma (58%), followed by bladder cancer (42%), endometrial carcinoma (35%), ovarian cancer (34%) and head and neck squamous cell carcinoma (34%). FGFR expression were promising predictive biomarkers for FGFR inhibition response in clinical trials and different combination of FGFR genes should be used in screening for patients in certain tumor types.
Citation Format: Yuan Li, Long Wu, Yanlei Cheng, Weiping Tao, Dawei Wu, Fei Ma, Ning Li. Expression atlas of FGF and FGFR genes in pan-cancer uncovered predictive biomarkers for FGFR inhibition response in clinical trials [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4882.
Abstract 4924: High ALDH1 expression in colorectal carcinoma could predict early onset of the disease
Authors: Vermani Litika , Kumar N Senthil , Talukdar Anuradha , Deka Monoj , Kannan Ravi , Kumar Rajeev 
Published: August 2019

Abstract
Background: Worldwide there is an increase in the trend of early onset of colorectal carcinoma in individuals who are less than 45 years of age. The composition of young age colorectal cases ranges from 35% to 40% in India. Currently, we do not have the access to any molecular marker that could predict early onset of the disease and its clinical course. Aldehyde dehydrogenase 1 (ALDH1), Twist, E Cadherin and Vimentin are markers for cancer stem cells and epithelial mesenchymal transition. However, there is paucity of data on their clinical significance in terms of their impact on early onset of colorectal carcinoma. This lack of data prompted us to investigate their role in the early onset of the colorectal cancer.
Methods: Immunohistochemisty of ALDH1, Twist, E Cadherin and Vimentin was performed in pre treatment biopsy samples collected from 103 colorectal patients who were further divided into 2 groups: viz, less than or equal to 45 years and more than 46 years.
Results: Over expression of ALDH1, Twist, E Cadherin and Vimentin was observed in 75.7%, 90.3%, 92.2% and 2.9% of pre treatment colorectal carcinoma tissue specimens respectively. ALDH1 expression was found to have strong correlation with early onset of the disease (patients who were less than or equal to 45 years of age (P=0.003). Women patients were found predominantly non smokers (P=0.001) and non tobacco chewers (P=0.004) with respect to men.
Conclusion: High ALDH1 expression correlates with the early onset of colorectal cancer. None of other markers could reach statistical significance with the early or late onset of colorectal cancer.
Note: This abstract was not presented at the meeting.
Citation Format: Litika Vermani, N Senthil Kumar, Anuradha Talukdar, Monoj Deka, Ravi Kannan, Rajeev Kumar. High ALDH1 expression in colorectal carcinoma could predict early onset of the disease [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4924.
Abstract 4938: Identification of a subtype of hepatocellular carcinoma with poor prognosis based on expression of genes within the glucose metabolic pathway
Authors: Zhang Xiaoli , Ghoshal Kalpana , Li Lang 
Published: August 2019

Abstract
Hepatocellular carcinoma (HCC) is the most prevalent primary cancer and a highly aggressive liver malignancy. Liver cancer cells reprogram their metabolic pathways to meet their needs for rapid proliferation and generation of the biomass for tumor growth. The accelerated aerobic glycolysis in tumor has been considered one of the hallmarks that distinguish cancer cells from normal cells. In the present study, liver hepatocellular cancer dataset of the Cancer Genome Atlas (LIHC TCGA) and datasets from Gene Expression Omnibus (GEO) were used to investigate the alterations in expressions of the genes involved in the glucose metabolic pathways as well as their association with the patient clinical stage and survival in liver cancer. In this study, 97 genes including glucose and lactate transporters, the enzymes involved in glucose metabolism (glycolysis, gluconeogenesis, regulation of glucose metabolism, tricarboxylic acid cycle (TCA), pentose phosphate pathway), and glycogen metabolism (glycogen synthesis, glycogen degradation, regulation of glycogen metabolism) were included. The results showed that the expressions of around 50% of genes involved in the glucose metabolic pathway are altered in liver tumors compared to the corresponding normal tissues (p-values&lt;0.005 and fold change≥1.5). More importantly, the differentially expressed genes are associated with advanced AJCC (American Joint Committee on Cancer) clinical stage (p-values&lt;0.05), and reduced overall survival (OS) and recurrence-free survival (RFS) as determined by multivariate Cox proportional hazard models (p-values&lt;0.05). Unexpectedly but interestingly, supervised clustering with the differentially expressed genes of the LIHC TCGA data identified a subgroup of patients with worse OS compared to those patients that clustered with the normal samples (p-value=0.00015, and 5-year median survival time (months) is 25.50 with 95% CI (20.90, 42.37) vs. 47.43 with 95% CI (40.33, NA)). This group of patients had decreased activation (p-values&lt;0.0001) of FXR/RXR and LXR/RXR involved in lipid, cholesterol and glucose metabolism, but had increased atherosclerosis and leukocyte extravasation signaling (p-values&lt;0.0001) activated during inflammation. This indicates those patients had decreased metabolism and increased inflammation which may contribute to the worse OS. Collectively, this study indicates that expressions of the glucose metabolic genes could be used as potential prognostic markers as well as therapeutic targets for liver cancer.
Citation Format: Xiaoli Zhang, Kalpana Ghoshal, Lang Li. Identification of a subtype of hepatocellular carcinoma with poor prognosis based on expression of genes within the glucose metabolic pathway [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4938.