bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of expression of FIP200 protein in progression of hepatocellular carcinoma
Authors: Ueda H. 
Published: August 2020

e22147 Background: FIP200 protein is a newly identified protein, and recent report has shown that FIP200 interacts with p53 and inhibit progression and proliferation. Although expression of FIP200 has been confirmed in normal liver,the expression and function in human HCC is completely unknown. In this study, we examined expression of FIP200 in HCC cell lines and investigated the involvement of FIP200 in proliferation and apoptosis. We also examined expression of FIP200 using HCC tissues and the correlation between FIP200 expression and clinical outcome. Methods: The study was conducted using HCC cell lines (HepG2, HuH7, and Hep3B). P53 status in HepG2, HuH7 and Hep3B are wild type, mutant type and deficient types respectively. Expression of endogenous FIP200 was assessed by western blotting. To investigate antitumor function, we carried out BrdU incorporation assay with transfected FIP200. TUNEL was carried out for identification of apoptosis. We also reviewed 14 patients who had undergone initial liver resection for HCC. Immunohistochemistry analysis for FIP200 was performed and we investigated the FIP200 expression levels according to differentiation degree of HCC tissues. Results: Endogenous FIP200 was detected in all cell lines, and those expression levels were different among cell lines. Overexpression of FIP200 significantly decreased BrdU incorporation in HepG2 and HuH7 but not Hep3B. In the study of TUNEL, apoptosis was observed for p53 wild HepG2 transfected with FIP200. In Hep3B, there was no significant difference observed. As for clinical samples, FIP200 were detected in all HCC and non-HCC tissues. FIP200 expression levels in HCC tissues were decreased compared to non-HCC tissues. Furthermore, as differentiation degree poored, those expression levels were decreased in the same tissue as well as in the different tissue. Conclusions: Endogenous FIP200 was expressed in all cell line. Those expression levels were different according to p53 status. Our study demonstrated that FIP200 inhibit proliferation in HCC expressed p53, and induce apoptosis in p53 wild HCC but not p53 deficient HCC. Furthermore, the FIP200 expression levels were significantly associated with differentiation degree. These data suggest that FIP200 plays an important role in promoting tumor progression in HCC. No significant financial relationships to disclose.
A genomic and transcriptomic approach to distinguish primary and metastatic ovary tumors
Authors: Meyniel J. , Cottu P. H. , Stern M. , Lebigot I. , Mignot L. , Roman-Roman S. , Sastre-Garau X. 
Published: August 2020

e22150 Background: Distinction of primary ovarian tumors from metastatic tumors involving the ovary is in some cases challenging for final pathologic diagnosis and for treatment with efficient chemotherapy Methods: We gathered from our biobank 16 pairs of breast/ovarian tumors for some of which the diagnosis was uncertain. We investigated the possibility to improve diagnosis using genomic and transcriptomic tools. The pangenomic profiles of 16 pairs of primary breast carcinoma and ovary tumors (primary tumors or metastases from breast carcinoma) from the same patients were analyzed using the Affymetrix GeneChip Mapping 50K (XbaI) SNP arrays. The data were normalized with ITALICS algorithm. We analyzed the transcriptome of the paired samples using Affymetrix U133plus2 arrays. The data were normalized with GCRMA algorithm and a hierarchical clustering of these samples was performed, together with a dataset of primary and secondary ovary tumors. Results: Primary infiltrating lobular carcinoma (ILC) was observed in 6 patients, infiltrating ductal carcinoma (IDC) in 7 patients, 1 patient had one ILC and one IDC, 1 patient had a mixed IDC+ILC and 1 patient an undifferentiated cancer. All patients received adequate loco-regional and systemic therapies. Median time to diagnosis of ovarian tumor was 54 months. Ovarian tumors were considered as primary in 7 patients, and metastatic in 9 patients, and diagnosis was ambiguous in 4 of them. Four patients developed extra-abdominal metastases. Median survival from breast cancer diagnosis was 78 months, and from ovarian tumor diagnosis was 29 months. CGH array: In 12 pairs, the comparison of genomic profiles one with each other, confirmed the pathological characteristics of the tumors. In 4 cases, the genomic profiles established clearly the status of the ovary tumor whereas the pathological analysis did not. Transcriptome: The status established by the transcriptomic analysis was for each sample in total agreement with the status established by the genomic analysis. Conclusions: We clearly established in this training series that CGH array analysis could help to discriminate between primary and secondary ovarian tumors from breast cancer. Transcriptomic data confirmed these results. Further validation data are warranted. No significant financial relationships to disclose.
Compliance and toxicity profiles of the CARISSA trial of postoperative cisplatin-based chemoradiation ± gefitinib in head and neck cancer
Authors: Thariat J. , de Raucourt D. , Giraud P. , Peyrade F. , Dassonville O. , Cosmidis A. , Dolivet G. , Calais G. , Santini J. , Bensadoun R. 
Published: August 2020

e22152 Background: Concurrent cisplatin and postoperative irradiation (PORT) is the standard treatment for resected poor-risk squamous cell carcinoma of the head and neck (HNSCC) . However, a substantial number of patients fail to respond. Anti-EGFR agents, such as gefitinib, may improve outcomes and molecular markers might predict treatment efficacy. This was the basis for the CARISSA trial. There was some concern after hemorrhagic events occurred in a large independent trial of recurrent unresectable HNSCC. This caused a temporary interruption and safety profile analysis of CARISSA, which resumed after security reports showed no excess of hemorrhagic events. Methods: The CARISSA multicenter blinded randomized phase II trial compares PORT and cisplatin alone (arm A) or in combination with the EGFR Inhibitor ZD1839 gefitinib (arm B) in HNSCC and analyses EGFR-binding, gene polymorphisms, Western Blotting and immunohistochemistry. Patients are followed weekly. Toxicities are graded according to the NCI/CTCv.3 scale. Results: Thirty-eight patients have been included. Compliance to cisplatin was 56% in arm A and 44% in arm B (NS). Compliance to gefitinib was 60% with half cases interrupting treatment for toxicity. There were 18 and 20 grade (G) 3/4 non-hematological toxicities, 12 and 6 hematological G3/4 toxicities in arms A and B, respectively. Mucositis was the most common toxicity. G3 mucositis occurred in 4 and 5 cases in arms A and B, dermatitis in three cases in each arm and diarrhea in one case in each arm (NS). There were 7 cancer- related deaths and 3 of other causes. One tumor-bleeding event occurred in the arm without gefitinib. Full-dose radiotherapy was delivered in all but one case in each arm. Mean doses were 63.9 ± 1.9 (arm A) and 65.5 ± 0.9 Gy (arm B) or 64.7 ± 0.9 (arm A) and 65 ± 0.9 Gy (arm B) in groups where RT was uninterrupted or temporarily interrupted, respectively (NS). The two patients who did not receive full dose received 60 Gy. Conclusions: Compliance to PORT was similar with cisplatin alone or cisplatin + gefitinib. While there was no excess of hemorrhagic morbidity postoperatively (no gross disease), accrual continues with particular caution. No significant financial relationships to disclose.
Clinical and pathologic correlation of p73 expression in surgically staged endometrial cancer
Authors: Resnick K. E. , Suarez A. , Nagel C. , Cohn D. , O'Malley D. 
Published: August 2020

e22153 Background: p73 is a p53 homologue that has been implicated both as a tumor suppressor and oncogene. While known to play a role in the apoptotic response, homozygous p73 knockout mice have not shown an increased susceptibility to tumor formation. However, recent literature suggests that p73 dysregulation may play a role in retinoblastoma, ovarian and bladder cancer. We sought to correlate p73 status with clinical-pathologic factors including mismatch repair status, in a large cohort of comprehensively staged endometrial cancers. Methods: Primary endometrial and colon cancers were used to create a tissue microarray (TMA). Two-hundred eight endometrial specimens were available for evaluation. Immunohistochemistry with p73 was performed using commercial available antibodies. Positive staining was defined as > 10% cells having positive nuclear staining. Microsatellite (MSI) instability testing as well as IHC for p53 had been previously performed. Statistical analysis was performed using Fisher's exact test. Results: In six non-neoplastic control endometrial samples examined, p73 appears to stain mainly surface epithelial cell nuclei and superficial glands. p73 expression was identified in 71 (34%) of endometrial cancer specimens. There was no correlation between p73 status and histology, stage, grade or MSI status. Strong correlation that was noted between p53 status and p73 status. Ninety-eight (71%) of the 137 p73 negative tumors were noted to be wildtype(negative staining) for p53 (p<.001). However, when the (-)p73 (+)p53 and (+) p73 (+)p53 phenotypes were examined separately, there was no correlation with stage or grade. Conclusions: p73 is a p53 homologue with uncertain potential as an oncogene and tumor suppressor gene. To date, we offer the largest study of p73 expression in comprehensively staged endometrial cancer. While we show significant loss of p73 expression among cancer specimens, we were unable to demonstrate a relationship between p73 and clinical factors. However, an interesting correlation between p53 status and p73 does appear. The potential role for p73 and p53 in the apoptotic response to cytotoxic chemotherapy is interesting and deserves further study. No significant financial relationships to disclose.
Circulating tumor cells in locally advanced breast cancer
Authors: García-Sáenz J. A. , Martín M. , Maestro M. , Vidaurreta M. , Veganzones S. , Rafael S. , Casado A. , Bobokova J. , Sastre J. , Arroyo M. , Diaz-Rubio E. 
Published: August 2020

e22159 Background: A prospective study was conducted to determine the value of changes in circulating tumor cell (CTC) levels prior to and after the first cycle of neoadjuvant treatment in early prediction of pathologic response in locally advanced breast cancer (LABC). Methods: Two blood samples were obtained from 72 eligible LABC patients to isolate and enumerate CTCs before neoadjuvant chemotherapy started on day 1, and on day 21, immediately before second cycle administration. Results: Sixty patients (83.3%) had ≤1 CTC in the first sample and response rates in this cohort were: pathologic complete response (PCR) in 2 patients (5%); partial response (PR) in 35 (87.5%); stable disease (SD) in 2 (5%); progressive disease (PR) in 1 (2.5%). Twelve patients (16.7%) had ≥2 CTCs in the first sample; these patients were more likely to have triple negative tumors. All 12 had fewer CTCs in the second sample. Response rates in this second cohort of 12 patients were: PCR in 4 (34%); PR, 6 (50%); SD, 1 (8%); and PD, 1 (8%). pCR rate was markedly better in this second cohort (p<0.0042; OR 14.5, 95% CI 2.3–92). Conclusions: This study suggests that the presence of CTCs prior to neoadjuvant therapy might be a predictor of response to this therapy. No significant financial relationships to disclose.
Immunohistochemical characteristics of breast cancer in Kazakh and Russian populations
Authors: Malyshev N. V. , Kulishov V. A. , Perminov V. S. , Sirota V. B. 
Published: August 2020

e22162 Background: Ethnic differences of breast cancer were satisfactory investigated in different populations of the United States and some important findings were revealed. In other areas of the world amount of similar studies is relatively low. Our aim was to investigate the ethnical differences in the expression of standard immunohistochemical markers of breast cancer between two main nations of Kazakhstan and to reveal possible correlations between these markers and prognosis of the patients. Methods: 664 breast cancer patients, treated in Karaganda Regional Cancer Center during 2006–2007, were included in this study (222 patients of Kazakh population and 442 patients of Russian population). Immunohistochemical expression of estrogen and progesterone receptors (ER and PR) and Her2/neu was determined in all patients. Expression of steroid receptors was counted as positive if staining was presented in more than one percent of breast cancer cells. Her2/neu expression was divided in two groups: 0, 1+ - negative expression, 2+, 3+ - positive expression. The obtained data was calculated and processed by statistical program - Statistica 6.0. Results: Breast cancer in Kazakh patients demonstrated higher level of Her2/neu positive expression (31.5% versus 23.8, p<0.05) and lower level of isolated ER and PR expression (36.5 versus 44.3, p=0.05). Still, breast cancer in Russian patients was more frequently associated with basal phenotype (15.2 versus 9.5, p<0.05).Strong inverse correlation was observed between age of patients and Her2/neu status (p=0.0005) and direct correlation between age and positive expression of steroid receptors (p<0.05). These correlations were observed in both populations. Conclusions: Breast cancer in Kazakh population was statistically significantly associated with unfavorable prognostic and predictive immunohistochemical status, such as higher expression of Her2/neu and lower expression of steroid receptors. Nevertheless elder patients were more likely to have less aggressive disease, independently from population. No significant financial relationships to disclose.
Lung cancer prediction: Phase transitions and cell ratio factors
Authors: Kshivets O. 
Published: August 2020

e22170 Background: Search of precise prognostic factors for non-small lung cancer (LC) patients (LCP) was realized. Methods: In trial (1985–2008) the data of consecutive 490 LCP after complete resections R0 (age=56.7±8 years; m=439, f=51; tumor diameter: D=4.5±2.1 cm; pneumonectomies=206, lobectomies=284, combined procedures with resection of pericardium, atrium, aorta, VCS, carina, diaphragm, ribs=130; squamous=308, adenocarcinoma=147, large cell=35; T1=143, T2=217, T3=107, T4=23; N0=282, N1=115, N2=93; G1=114, G2=140, G3=236; early LC: LC till 2 cm in D with N0=58, invasive LC=432) was reviewed. Variables selected for 5-year survival (5YS) study were input levels of blood cell subpopulations, TNMG, D. Neural networks computing, Cox regression, clustering, structural equation modeling, Monte Carlo and bootstrap simulation were used to determine any significant regularity. Results: For total of 490 LCP overall life span (LS) was 1824±1304 days (median=1879) and real 5YS reached 62%, 10 years - 50.3%, 20 years - 45.3%. 304 LCP (LS=2597.3±1037 days) lived more than 5 years without LC progressing. 186 LCP (LS=559.8±383.1 days) died because of LC during first 5 years after surgery. 5YS of early LCP was significantly superior (100%) compared with invasive LCP (56.9%) (P=0.000 by log-rank test). 5YS of LCP with N0 was significantly better (78.4%) compared with LCP with N1–2 (39.9%) (P=0.000). Cox modeling displayed that 5YS significantly depended on: phase transition (PT) in terms of synergetics “early-invasive LC”, PT N0-N12, histology, G1–3, cell ratio factors: ratio between the total populations of leucocytes, lymphocytes, neutrophils and LC cells (P=0.000–0.044). Neural networks computing, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT “early-invasive LC”, (rank=1), PT N0-N12 (2), histology (3), G1–3 (4), T1–4 (5), ratio of lymphocytes/LC cells (6), healthy cells/LC cells (7), erythrocytes/LC cells (8), thrombocytes/LC cells (9), eosinophils/LC cells (10), neutrophils/LC cells (11). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; urea under ROC curve=1.0). Conclusions: 5YS of LCP after radical procedures depended on: 1) PT “early-invasive LC”; 2) PT N0-N12; 3) cell ratio factors; 4) LC characteristics. No significant financial relationships to disclose.
Chemokine receptor CXCR4 expression and its regulation in gastric cancer cells
Authors: Lee H. , Kim H. , Kim S. , Yun H. , Kim S. , Jo D. 
Published: August 2020

e22173 Background: The chemokine receptor CXCR4 is associated with the biological behavior in several kinds of cancer, but few studies have addressed the expression and regulation of CXCR4 in gastric cancer. Methods: Five gastric cancer cell lines were studied. The expression of CXCR4 was investigated using RT-PCR, Westerning blotting, flow cytometry, and immunofluorescence staining. The regulation of CXCR4 expression by hypoxia, dexamethasone, and the proinflammatory cytokines was evaluated. Results: CXCR4 mRNA and proteins were detectable by RT-PCR and Western blot analysis, respectively, in all five cell lines. However, MKN-28, MKN-45, MKN-74, and SNU 16 cells did not express membrane CXCR4, but had abundant CXCR4 in their cytoplasm, as determined by flow cytometry and immunofluorescence staining. In contrast, a small population of KATO III cells expressed membrane CXCR4. Hypoxia up-regulated CXCR4 proteins and enhanced membrane expression of CXCR4 in human gastric cancer KATO III cells, which constitutively expressed membrane CXCR4 in a steady state, as revealed by Western blotting and flow cytometry, respectively. This hypoxia-induced expression of CXCR4 was mediated via hypoxia-inducible factor (HIF)-1α. In addition, KATO III cells exposed to hypoxia demonstrated enhanced migration in response to stromal cell-derived factor (SDF)-1α, a specific ligand for CXCR4. However, MKN-28, MKN-45, MKN-74, and SNU-16 cells, which lack membrane CXCR4 in a steady state, showed no change in CXCR4 expression in hypoxic condition. Treatment with IFN-γ, TGF-β, TNF-α, and dexamethasone did not induce any change in CXCR4 expression in all five gastric cancer cells. Conclusions: This study suggests that hypoxia up-regulates the membrane expression of functional CXCR4 via HIF-1α in human gastric cancer cells that basally express membrane CXCR4 in a steady state in vitro. No significant financial relationships to disclose.
Comorbidity prior to diagnosis in patients with common cancer diagnoses
Authors: Olsson H. , Attner B. , Noreen D. , Lithman T. 
Published: August 2020

e22180 Background: Chronic disease as diabetes, hypertonia and anemia may be associated with cancer risk as well as affect the short term survival of the malignancy. Methods: Using population based registry data from specialist and primary care in our health care region comorbidity in the form of anemia, hypertonia, diabetes, rheumatoid arthritis, chronic obstructive pulmonary diasease (KOL), and alcohol related diseases for patients with colon-, rectal-, lung-, prostate and breast cancer and survival were studied. Altogether 2047 colon cancer cases, 985 rectal cancer cases, 2017 lung cancer cases, 3578 breast cancer cases and 5106 prostate cancer cases diagnosed 2000–2005 were included. Results: were age and sex adjusted and one year survival was calculated. Comorbidity was studied prior to cancer diagnosis and in order to compare with the general population all first comorbidity diagnoses within 90 days were censored. Results The prevalence of the chronic diseases in the general population was for all ages diabetes 3.2%, rheumatoid arthritis 0.5%, hypertonia 6.8%, anemia 1.1%, KOL 1.0% and alcohol related diagnoses 0.7%. Patients with colon and rectal cancer had a higher prevalence of anemia, and diabetes. Patients with lung cancer had a higher prevalence of anemia, KOL, diabetes, rheumatoid arthritis for both men and women and for men also a higher prevalence of alcohol related diseases. Except for alcohol related diseases in females with breast cancer comorbidity for the above diseases was not significantly elevated for breast or prostate cancer. For all diagnoses hypertonia was significantly lower than in the general population. Survival of the different cancer diagnoses was not significantly related to the comorbidity except for a tendency of worse survival for patients with alcohol related disease. Conclusions: The prevalence of some common chronic diseases are elevated especially in colon-, rectal and lung cancer patients. The comorbidity does not seem to affect short term survival of the cancer patient except for alcohol related diagnoses. Our study also indicates the necessity to have all levels of care included in the study base of comorbidity and also emphasizes the need to censor time prior to diagnosis when comparing data with the general population. No significant financial relationships to disclose.
Characteristics of bone mineral density at the time of diagnosis in postmenopausal breast cancer patients
Authors: Kim H. J. , Park E. , Lim W. , Sei J. , Koh B. , Son B. , Ahn S. 
Published: August 2020

e22187 Background: Bone mass has been proposed as a marker of cumulative exposure to estrogen in women. We have studied the association between bone mass and breast cancer in postmenopausal women. Methods: We investigated the association between bone mineral density(BMD), as measured at the lumbar spine and femoral neck and the breast cancer in women age 50 or older, who were received an initial diagnosis of stage 0-III breast cancer, confirmed by pathologic assessment of breast tissue. We recruited 718 women with newly diagnosed breast cancer in a Asan Medical Center from 1, Jun. 2006 to 31, Dec. 2007. BMD was measured by lunar EXPERT-XL for breast cancer patients Results: Median age at diagnosis was 58 (range 47–82). Patients with higher BMD at lumbar spine were found to have low grade disease (p<0.005). The patients with hormone receptor positive breast tumor showed higher BMD at lumbar spine and lower serum 25(OH)D than hormone receptor negative tumor. Serum estradiol level did not show a relation to BMD. There were no significant differences between breast cancer stage and serum 25(OH)D and BMD. Conclusions: The patients who have hormone receptor positive breast cancer had higher Lumbar spine BMD and lower 25(OH)D than hormone receptor negative patients. No significant financial relationships to disclose.
Contribution of BRCA1 and BRCA2 mutations to breast cancer in Tunisia
Authors: Wafa T. 
Published: August 2020

e22191 Background: Hereditary breast cancer accounts for 3–8% of all breast cancers. It was recently estimated that a combination of BRCA1 and BRCA2 genes mutations is responsible for 30% of hereditary breast cancer cases. Methods: To investigate the prevalence of BRCA1 and BRCA2 gene mutations in breast cancer patients with affected relatives in Tunisia, 36 patients who had at least one first degree relative affected with breast and/or ovarian cancer were analysed. Thirty three patients are suggestive of BRCA1 mutation and 3 are suggestive of BRCA2 mutation. Results: Four mutations in BRCA1 gene were described among which, one novel splice site mutation (330 dupA) and 3 frameshift mutations including the 4160 delAG, the 2789 delG and the 5385 insC. Our study is the first to describe the 5385 insC mutation which was described only among Jewish Ashkenazi population. Two frameshift mutations (1537 del4 and 5909 insA) were screened in BRCA2 gene. Nineteen percent (7/36) of the familial cases were altered on BRCA1 or BRCA2 genes with deleterious mutations at heterozygous state and 55% (20/36) by mutation with uncertain value (UV) or by single nucleotide polymorphisms (SNPs). Conclusions: Almost all the cases mutated by deleterious mutations on BRCA1 gene reported a family history of breast and/or ovarian cancer in the index case or in their relatives. On the contrary, patients with an UV mutation or SNPs have no history of ovarian cancer in their corresponding families. Our data are the first to contribute to information on mutation spectrum of BRCA genes and offer a recommended screening mode for clinical genetic testing policy in Tunisia. No significant financial relationships to disclose.