bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical significance of ERas oncogene on cancer
Authors: Yasuda K. , Yashiro M. , Sawada T. , Ohira M. , Hirakawa K. 
Published: March 2020

15083 Background: Embryonic stem (ES) cells are pluripotent cells derived from early mammalian embryos. When ES cells are subcutaneously injected into immunodeficient or isogenic mice, a teratoma is formed within a few weeks. This tumor is composed of all three germ layers in a disorganized fashion. Thus there could be some common molecular mechanisms shared by ES cells and somatic cancer cells. The ERas oncogene is a recently identified gene that supports the tumorigenic growth of ES cells by producing a constitutively active Ras protein. There have been no report about expression of ERas oncogene on cancer cells until now. The aim of this study is to investigate expression and clinical significance of ERas oncogene on cancer cell lines and clinical cancer tissues. Methods: A panel of 35 human cancer cell lines, 5 normal cell lines, and 20 patiants with gastric cancer tissues were used in this study. ERas mRNA expression was examined by reverse transcription-polymerase chain reaction. The effect of the DNA methyl transferase inhibitor, 5-aza-2’- deoxycitydine on the ERas expression was analyzed. Methylation of CpG islands of ERas promoter lesion was investigated using bisulfate-directsequence analysis. Results: Expression of ERas mRNA was not found in any normal cells. In contrast, ERas mRNA was found in 15 of 35 cancer cell lines, including 8 of 15 gastric cancers, 4 of 7 colorectal cancers, 2 of 6 pancreas cancers, 1 of 3 breast cancers and none of esophageal cancers. Eras mRNA was found in all gastric cancer tissues, but not normal tissues. 5-aza-2’-deoxycytidine treatment at 2, 5, and 10μM for 24 h resulted in ERas expression in 10 of 20 cancer cell lines with respect to the silencing of ERas, including 7 of 7 gastric cancers, 1 of 3 colorectal cancers and 2 of 3 breast cancers. Methylation of CpG island were found in the cancer cell lines without ERas expression, but not in these with ERas expression. Conclusions: ERas oncogene is associated with the carcinogenesis pathway in human cancer. Eras might be useful marker for cancer diagnosis. No significant financial relationships to disclose.
Neoadjuvant and combined chemoradiotherapy followed by surgery in locally advanced esophageal cancer: A single-centre experience
Authors: Diaz R. , Reynes G. , Tormo A. , Segura A. , Santaballa A. , Ponce J. , Giménez A. , De Juan M. , Artes F. , Fleitas T. 
Published: March 2020

15086 Background: Concomitant chemoradiotherapy (CT-RT) with CDDP-5FU CT is a standard treatment in locally advanced esophageal cancer (EC). Long-term results are poor. The role of neoadjuvant CT (nCT) and of radical surgery after CT-RT is unclear. Methods: Single-institution, prospective trial in pts with stage II-IVA EC (TNM). PS 0–1. Staging: CT scan, barium x-ray, esophagoscopy and endoscopic ultrasound. Treatment schema: 1 cycle of neoadjuvant CT (CDDP 100 mg/m2 d1 and 5-FU 1,000 mg/m2/24 h d1–5); after 21 days, 50 Gy of RT (1.8 cGy/day, M to F) and 2 cycles of reduced-dose CT (CDDP 15 mg/m2 d1–5 and 5-FU 800 mg/m2/24 h d1–5, q21 days). In pts deemed resectable, surgery was done after 4–6 weeks. In the remainder, a 10 Gy boost was given with 1 cycle of modified CT. Primary endpoint: clinical and pathological response rate (RR) after 1st phase. Secondary endpoints: OS and toxicity rates. Results: 71 pts accrued between 1998 and 2006. Median age 61 yrs (r 44–80). 96% males. 85% squamous cell carcinomas. Middle third: 51%; upper third: 27%; lower third 22%. Gastric involvement: 11%. cT3: 46%, cT4: 28%. cN positive: 48%. Grade 3–4 toxicity with nCT and CT-RT: mucositis (9 and 19.5%), emesis (9 and 9%) and infection (6 and 9%). Full dose CT-RT: 87%. Clinical RR after 1st phase: CR 50%, PR 25%, SD 9%, PD 7%. Confirmation (CT- biopsy): 69%. Surgery: 30%. Reasons for no surgery: comorbidity (11%) and age (10%). Pathologic RR: CR 39%, microscopic rest 39% and macroscopic rest 22%. Downstaging 50%. No pN positive. 3 pts had unresectable disease. 62% received 2nd phase RT boost, 31% with CT. Clinical RR: CR 69%, PR 6%, PD 25%. Median follow-up 50 m (r 6–129 m). Median OS 10.5 m (r 7.4–12.8 m). 4-year OS of 18%. 47% deaths due to progression, 5% treatment-related deaths and 10% in the postoperative period. Only a clinical CR after 1st phase was found to improve OS (13.5 vs 7 m, p 0.0141). Conclusions: This regimen is well tolerated and offers a high response rate. Clinical response evaluation overestimates the pathologic response rate. In our series, the possible survival benefit of surgery is offset by the postoperative death rate. No significant financial relationships to disclose.
Comparison of gross tumor volume delineated by anatomic imaging and FDG PET/CT for esophageal carcinoma and validation with pathological specimen
Authors: Yu J. M. , Zhong X. J. , Zhang B. J. , Mu D. B. , Han A. Q. , Sun X. D. , Yuan S. H. , Song P. P. , Li H. , Fu Z. 
Published: March 2020

15090 Background: Although results of clinical studies have demonstrated FDG PET/CT improved target volume delineation in various tumors, only few studies compared delineation based on PET/CT with pathologic examination. Aim of our study was to compare anatomic imaging modalities including computed tomography (CT), esophagram, endoscopy with FDG PET/CT for delineation of gross tumor volume (GTV) in esophageal carcinoma and to validate the results with the pathologic examination. Methods: Thirty patients with stages II-III squamous cell carcinoma underwent transthoracic esophagectomy were enrolled. PET/CT, esophagram and endoscopy were performed with patients before operations. The length of the lesion on the PET/CT scan and on the CT portion of the PET/CT and the PET scan alone was determined independently by 3 separate investigative groups. PET/CT scan was evaluated by visual inspection for abnormality. A standard uptake value (SUV) of 2.5 was used in the PET scan to delineate the tumor extent. The lengths of GTVs determined with the five modalities (PET/CT, PET, CT, esophagram and endoscopy) were compared quantitatively and validated with the pathologic specimen. The sizes of the tumors were measured by pathologic examination which was considered as the gold standard. Results: Of the 30 patients, 9 had T2 tumors, 20 had T3 tumors and 1 had T4 tumor with an involvement of pleura. Three tumors were located at the upper esophagus, 14 at the middle esophagus, 13 at the lower esophagus. The mean length of the carcinoma was 5.85cm(SD 2.50cm) measured by pathologic examination, 5.79cm (SD 2.04cm) as determined by PET scan, 5.14cm (SD 1.65cm) by PET/CT scan, 5.42 cm(SD 2.42cm)by CT scan, 5.50cm(SD 2.79cm) by endoscopy, and 6.07cm(SD 2.75cm) by esophagram respectively. Although the lengths of the tumors as measured by the five imaging modalities were no significant difference, the result of PET was the most accurate. Conclusions: Compared with tumor lengths measured by pathologic examination, PET with a SUV 2.5 was found to be the most accurate modality and can help the radiation oncologist delineate the GTV of esophageal carcinoma precisely. No significant financial relationships to disclose.
Adjuvant treatment in resected pancreatic adenocarcinoma: A retrospective analysis of survival and prognostic factors in 141 patients
Authors: Bujold A. , Létourneau R. , Lapointe R. , Dagenais M. , Roy A. , Lambert C. , Donath D. , Fortin B. , Tardif M. , Jolicoeur M. 
Published: March 2020

15104 Background: Resectable pancreatic adenocarcinoma (PA) remains highly lethal. It is debatable whether adjuvant therapy can improve prognosis. Furthermore, what treatment should be delivered and for whom it is indicated is still of controversy. Methods: Between 1992–2004, retrospective data from the 141 patients who had a PA resected with curative intent in our centres were reviewed. Adjuvant treatment was as follows: 41 had chemoradiation (CRT), 1 neoadjuvant CRT, 10 chemotherapy alone (CT), 1 radiotherapy alone, and for 7 adjuvant treatment is unknown. The other 81 patients were observed. Overall survival (OS), relapse-free survival (RFS), locoregional and distant failure-free survival (LRFFS and DFFS) were analysed according to published prognostic factors. Kaplan-Meier curves with log-rank tests and Chi-2 coefficients were computed for the analysis. Results: Median age at diagnosis was 61 years. Overall, 63% of the patients were node positive, 67% had lymphovascular invasion (LVI), 71% had elevated CA-19.9 values and 50% operative blood loss >550cc. Table 1 displays these prognostics factors by treatment groups. For the entire cohort, median OS was 16.9 months; 1-year and 3-year OS were 76% and 43% respectively. No influence of treatment arm was found on OS (p=0.71). Negative nodes, normal CA-19.9 values, absence of LVI and blood loss <=550cc had all a positive influence on OS (all p<0.05). RFS and DFFS were not affected by adjuvant treatment (p=0.61 and 0.68, resp.), but a lower LRFFS was associated with it (p=0.006). Conclusions: In this retrospective analysis, despite the imbalance of prognostic factors among treatment groups, toward more ill patients in CT and CRT arms, there is no difference in OS, DFS and DFFS between arms. Therefore, adjuvant treatment seems to counterbalance the effect of poor prognostic factors. A randomized prospective trial would be needed to further address the issue. [Table: see text] No significant financial relationships to disclose.
The nuclear expressions of ERK1/2 and p38 can be useful markers for tumor invasiveness and lymph node metastasis in stomach cancer
Authors: Chang H. , Choi K. , Lee S. , Yoon K. 
Published: March 2020

15109 Background: Extracellular-regulated kinases (ERKs) were shown to have a function in cellular proliferation or differentiation and p38 were known as to be involved in apoptotic processes in tumor development. Tissue inhibitors of metalloproteinase(TIMP) have been known to be a important role in tumor cell invasion, which was postulated to be regulated by ERKs and p38. The clinical implication of ERKs and p38 on stomach cancer was investigated Methods: By immunohistochemistry with an antibody specific for dually phosphorylated ERK 1 /2 and 2 , TIMP-1 and -2, and p38 on formaline-fixed paraffin-embedded tissue, we have examined 57 primary stomach cancer consisting of 36 cases of intestinal type and 21 cases of diffuse type carcinomas. One-way ANOV(non-parametric) was used to compare differences among more three groups and paired T-test were used between groups.P<0.05 was considered as statistic significant. Results: The expression rate of ERK1/2 in the nuclei of the tumor cells was 21.5%, The expressions of ERK 2, TIMP-1 TIMP-2, were 56.4%, 50.9%, 61.4%. The expression rate of p38 in the tumor cells was 37.7%.. The p38 expression had significant correlation with invasion depth of tumor(p=0.016), lymph node metastasis(p=0.030), and TIMP-2 expression(p=0.038). ERK1/2 had significant association with tumor invasion(p=0.003), lymph node metastasis(p-0.013), tumor cell grades(p=0.030), and TIMP-1(p=0.029). ERK-2, TIMP-1 and 2 had no significant relationship to tumor invasion and metastasis Conclusions: These results suggest that the nuclear expressions of ERK1/2 and p38 can be the useful markers predicting the progression of stomach cancer towards invasiveness and metastasis No significant financial relationships to disclose.
Erythropoetin (epoetin beta) once weekly in anemic patients with advanced cancer of the stomach or gastroesophageal junction: Interim results of a randomized German AIO phase II trail
Authors: Moehler M. H. , Geissler M. , Raedle J. , Ebert M. , Scherubl H. , Flieger D. , Seufferlein T. , Galle P. , Kanzler S. ,   Upper-GI Group of German AIO
Published: March 2020

15133 Background: Tumor-related or chemotherapy-induced anemia is common in gastrointestinal cancer patients and results in reduced quality of life and worse prognosis. Thus, the effectiveness of erythropoetin (epoetin beta) treatment (EB) to achieve and maintain a target haemoglobin (Hb) level of ≥ 11 g/dl was assessed within a randomised German AIO phase II study to assess efficacy of irinotecan/capecitabine versus cisplatin/capecitabine in advanced gastric or lower esophageal cancer. Methods: Patients (pts) with untreated locally advanced or metastatic adenocarcinoma of stomach or gastroesophageal junction (KPS ≥ 60%, > one measurable lesion, adequate organ functions) were randomized to receive 3-weekly cycles of either irinotecan 250 mg/m2 d1 (arm A) or cisplatin 80 mg/m2 d1 (arm B). Capecitabine was administered at 2000 mg/m2 for 14 days in both arms. In both arms, EB (30,000 I.E. once weekly) was given at Hb of < 11 g/dl and continued until Hb ≥ 12 g/dl. If after 4 treatment weeks, Hb increase was < 0.5 g/dl, EB was increased to 30,000 I.E. twice weekly. FACT-An questionnaires were completed at each cycle. Results: At time of abstract submission, 81 pts were randomized to A (37 pts) or B (44 pts). 23 pts received at least 3 EB injections (A: 10 pts, B: 13 pts). Median Hb prior to EB was 10.5 g/dl (A: 10.4 g/dl, B: 10.5 g/dl) and median Hb at end of EB was 11.6 g/dl (A: 11.5 g/dl, B: 11.75 g/dl). During EB, 80 % of A and 77 % of B achieved target Hb of ≥ 11 g/dl with a median rise in Hb of 2.0 g/dl (A: 1.4 g/dl, B: 2 g/dl). 5 pts in A and 7 pts in B responded with a ≥ 1 g/dl rise in Hb during first 4 weeks. FACT-An questionnaires showed no change from baseline to end of EB. Among evaluable pts with EB (20 pts) versus without EB (34 pts), response (CR + PR) and tumor control rates (CR + PR + SD) were 60% vs 35% and 85% vs 70%, respectively. Conclusions: EB is effective in raising Hb levels in advanced or metastatic gastric cancer. Patients receiving EB tend to show a better response to chemotherapy. No significant financial relationships to disclose.
Two-fraction carbon ion radiotherapy for hepatocellular carcinoma
Authors: Kato H. , Yasuda S. , Yamada S. , Hara R. , Kano M. , Kamada T. , Mizoe J. , Tsujii H. 
Published: March 2020

15134 Background: In Japan, most patients with Hepatocellular Carcinoma (HCC) have liver cirrhosis, an advanced hepatic disorder, and they often require repeated therapies owing to the multicentric nature of carcinogenesis in the cirrhotic liver. Therefore, both radical effect and minimal invasiveness are essential for the treatment of HCC. However, there were no therapies satisfying both of these essential requirements for every-sized HCC. The purpose of this trial was to evaluate the safety and efficacy of two-fraction carbon ion radiotherapy (CIRT) for HCC. Methods: Eligibility criteria for this study were as follows: biopsy-proven HCC; recurrent or residual tumor after other ineffective treatments or no indication for any other treatment; no prior radiotherapy for target tumors; hepatic disorder of Child-Pugh grade A or B; Karnofsky performance status of 60–100; no other active cancer; and digestive tract not in contact with clinical target volume. CIRT was administered within dose escalation study of 32.0 to 38.8 cobalt gray equivalent (GyE) in 2 fractions for 2 days. Results: Between April 2004 and August 2006, 40 patients were totally enrolled. All patients had chronic liver diseases of Child-Pugh grade A in 37, B in 3. The median tumor size was 4.7 cm in diameter (2.0 to 6.7 cm). During a median follow-up of 32 months (range, 5–45 months), no hepatic failure resulting from the therapy and no treatment-related death occurred. Incidence of grade 3 early hepatic toxicity according to NCI-CTC ver.2 in the essential valuables concerning hepatic function was 0% in serum-GPT, ALB, prothrombin activity (PT%) and ALP, and 3% in T.BIL. No grade 4 toxicity has occurred. In 94% and 86% out of the patients, Child-Pugh score did not increase by more than 1 point in the early and late phases, respectively. In the lower-dose group (32.0, 33.6, 35.2 GyE: n=18), 2-year local control rate and overall survival rate were 71% and 83%, respectively. In the higher-dose group (37.0, 38.8 GyE: n=22), they were 100% and 90%, respectively. Conclusions: Although 2-fraction carbon ion radiotherapy seems to be safe and effective, and to have a promising potential as a new, radical, and minimally invasive therapeutic option for Hepatocellular Carcinoma, further careful follow-up is needed to confirm it’s clinical efficacy. No significant financial relationships to disclose.
Phase I/II study of PHY906/capecitabine in hepatocellular carcinoma
Authors: Rose M. G. , Yen Y. , So S. , Saif M. W. , Chu E. , Liu S. , Jiang Z. , Foo A. , Tilton R. , Cheng Y. 
Published: March 2020

15152 Traditional botanical formulations in combination with conventional antitumor chemotherapeutics may prove a powerful approach in reducing toxicity and improving clinical outcomes. In vivo studies show that PHY906, a traditional Chinese formulation, can reduce chemo-induced gastrointestinal toxicity while enhancing the therapeutic efficacy of a broad-spectrum of common anticancer agents in various cancer models, including capecitabine, CPT-11, thalidomide, adriamycin, and sorafenib in liver cancer; gemcitabine, capecitabine, oxaliplatin, gem/ox in pancreatic cancer; and CPT-11, 5-FU, sorafenib, VP-16, L-OddC, CPT-11/5-FU/LV, and oxaliplatin/5-FU/LV in colorectal cancer. Co- administration of PHY906 with a host of chemotherapeutic agents appears to neither alter the pharmacokinetic profiles of the chemotherapeutic agents nor their respective metabolites. PHY906 is currently being studied in a phase I/II, multicenter, open-label, dose-modification, safety and efficacy study in combination with capecitabine in patients with non-resectable HCC in the U.S. and Taiwan. Phase I patients (n=18) were enrolled at COH, Yale, VA and Stanford beginning November 2003. The primary objective of phase I was the determination of a safe dose regimen by varying the dose levels of PHY906 and/or capecitabine. Three dose levels of PHY906 + capecitabine were evaluated: PHY906 1000 mg BID + Capecitabine 1000 mg/m2 BID; PHY906 600 mg BID + Capecitabine 750 mg/m2 BID; and PHY906 800 mg BID + Capecitabine 750 mg/m2 BID. The final dosing level was chosen for the phase II portion of the study. Preliminary results suggest that the quality of life of patients on PHY906 + capecitabine was improved when compared to historical controls studying capecitabine alone. There is also no evidence of drug-induced toxicity caused by PHY906; nor does PHY906 reduce capecitabine antitumor activity. For patients receiving capecitabine at 750 mg/m2 BID and PHY906 at either 600 mg BID (N=4) or 800 mg BID (N=24), 10.7% (N=3) achieved minor response (MR), 50% (N=14) had stable disease (SD) and 39.3% (N=11) had progressive disease (PD). These findings support the further investigation of PHY906 as an adjuvant therapy of capecitabine in a larger HCC population. No significant financial relationships to disclose.
Rapamycin inhibits the growth of cholangiocarcinoma cells in vitro
Authors: Sawada T. , Okada T. , Kubota K. 
Published: March 2020

15153 Background: In the present study, anti-neoplastic effect of rapamycin against cholangiocarcinoma was studied in vitro. Methods: Expression of mTOR in 4 cholangiocarcinoma cell lines, TFK1, HuCCT1, NOZW, and OZ was evaluated by real-time PCR. Then, the four cholangiocarcinoma cell lines were cultured with rapamycin (0, 25, 50, 100, 200 nM), gemcitabine (0, 0.5, 1, 2 μM), or both, and anti-proliferative effect was evaluated by MTT assay. Results: All the four cholangiocarcinoma cell lines expressed endogenous mTOR- mRNA. Level of expression was the highest in HuCCT1 (65.8), and the lowest in TFK1 (17.6). Then, rapamycin significantly inhibited the growth of all the four cholangiocarcinoma cell lines, in dose-dependent manner. Gemcitabine inhibited the growth of NOZW (48.4%) and HuCCT1 (48.9%), but less efficiently in TFK1 (5.9%) and OZ (27.4%). Furthermore, synergistic anti-proliferative effect of rapamycin and gemcitabine was observed in TFK1 (39.1%), NOZW (38.9%), and OZ (47.1%), not in HuCCT1 (18.9%). Conclusion: Rapamycin effectively inhibited the growth of the cholangiocarcinoma cell lines, and synergistic effect with gemcitabine was observed in three of the four cell lines. No significant financial relationships to disclose.
A phase I dose escalation study of pharmacobiologically based scheduling of capecitabine and mitomycin C (MMC) in patients with gastrointestinal solid malignancies
Authors: Hill M. E. , Campbell A. , Kosuri K. , Thomas J. , Villalona M. , Bekaii-Saab T. 
Published: March 2020

15154 Background: A principal determinant of the therapeutic index of capecitabine-based treatment is the grade of thymidine phosphorylase(dThdPase) activity in malignant tissues. MMC, an agent that is active in gastrointestinal malignancies, produces significant upregulation of the dTHdPase starting 4–6 days after treatment and persisting for at least 10 days. On the basis of the time-dependency and transience of this upregulation, we performed a phase I study of capecitabine in combination with MMC. The aim was to determine the maximally tolerated dose of this combination. Methods: In this ongoing study, patients with advanced gastrointestinal solid malignancies received MMC on day 1 and capecitabine twice daily on days 8 and 21, every 4 weeks. The MMC dose was fixed at 6mg/m2, whereas capecitabine was escalated in successive patient cohorts. Patients were allowed to have had a maximum of 2 prior therapies for metastatic disease. The total cumulative dose of MMC was capped at 36 mg/m^2 to reduce the risk of cumulative toxicity. Results: So far 23 patients with a median age of 62 received capecitabine doses from 1000 to 2000 mg/m^2/d. The majority of the patients had at least 1 prior treatment (86%). Four patients were considered non-evaluable. No dose-limiting toxicities were observed as we reached our final dose level. Toxicities were generally mild with only 7 patients experiencing grade 3 toxicities and two experiencing grade 4 toxicities. The most common toxicities were fatigue (67%), nausea (43%), diarrhea (33%), and anemia (29%), and all toxicities were reversible. There were no objective responses; however, 32% of evaluable patients had prolonged stable disease (43% colorectal, 29% pancreas, 14% esophageal, and 14% gastric). Conclusions: Capecitabine in combination with MMC in the proposed schedule is well tolerated and has promising preliminary activity in various gastrointestinal malignancies. Recommended doses for phase II studies are capecitabine 1000 mg/m^2 twice daily and MMC 6 mg/m^2. This study is ongoing with 2 more patients being entered at the recommended phase II dose. No significant financial relationships to disclose.