bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regenerating gene 1α (REG 1α) expression and new treatment strategies in early non-small cell lung cancer
Authors: Tojo T. , Tojo T. , Naito H. , Kimura M. , Takasawa S. , Dohi Y. , Nagata Y. , Taniguchi S. 
Published: August 2020

e22178 Background: Regenerating gene (REG) I was originally isolated as an endogenous growth factor from pancreatic islet β cells. REG Iα protein is suggested to be involved in carcinogenesis in various gastroenterologic tissues. In the present study, to elucidate roles for REG Iα in non-small cell lung cancer (NSCLC), we investigated REG Iα expression in NSCLCs, focusing especially on its relationship with prognosis. Methods: We enrolled 70 NSCLCs (adenocarcinoma (AC)(n=48) and squamous cell carcinoma (SCC)(n=22)) who received surgery at Nara Medical University Hospital. Total RNA was extracted from each tumor tissue and corresponding normal lung tissue (NL)(n=70), cDNA was then reverse-transcribed from total RNA, and quantitative real-time reverse transcriptase-polymerase chain reaction was then carried out. The expression level of REG Iα in each sample was normalized with respect to that of β-actin, and the cutoff level was set at average+3SD expression of the 70 NLs. We also examined the relationship between REG 1α expression in the tumor tissue and the prognosis. Results: Six (12.5%) of the 48 ACs and 5 (22.7%) of the 22 SCCs were positive for REG Iα gene, and which is higher than that of NLs (2 of 70: 2.9%). After median follow-up of 26.2 months, 12 patients died due to disease progression. The survival rate among the REG 1α positive patients was significantly worse than among the REG 1α negative patients in ACs (P<0.05), and not significantly but worse in SCCs (P=0.07). In case of stage I, none of REG 1α negative patient died in both ACs and SCCs compared with 4 patients died of positive patients (AC:2, SCC:2), and also the survival rate among the REG 1α positive patients was significantly worse than among the negative patients in ACs (P<0.01) and SCCs (P<0.05). Disease free survival of REG 1α positive patients was also worse than negative patients in ACs (P<0.05) and SCCs (P=0.16). Conclusions: REG Iα expression in NSCLCs may be the risk factor for poor prognosis, and we anticipate that it will enable us to provide more appropriate and individualized treatment to patients of early NSCLC. No significant financial relationships to disclose.
APC allele-specific expression in carriers of Ashkenazi Jewish mutation I1307K
Authors: Capella G. , Castellsague E. , Rennert G. , Gruber S. 
Published: August 2020

e22181 Background: I1307K is a missense APC variant with incomplete penetrance that has been found in 6% of Jewish Ashkenazi population and confers a two-fold increased risk to develop multiple adenomas and colorectal tumours. It is believed that it creates a hypermutable region within the gene that leads to an accumulation of mutations. It remains unknown whether the presence of this mutation modifies APC expression. Our goal was to study whether allele-specific expression (ASE) of I1307K is present at the germline and tumoral level. Methods: Paired germline/carcinoma RNA and DNA was studied from eleven I1307K carriers. To analyze changes in the mutant/wt allelic ratio we used single nucleotide primer extension (SNuPE) for the I1307K and the rs2229992 APCcoding SNP. Fourteen controls were also analyzed. Results: No germline allele specific expression was found in I1307K carriers (range=0.954–1.173). Significant ASE was observed in 8 of the 10 carcinomas analyzed. In 4 cases the I1307K allele was overexpressed (range=2.51–9.51) and in 4 cases was underexpressed (range=0.09–0.28). Tumor ASE correlated with the DNA mutant/wt allelic dose. Conclusions: I1307K variant is not associated with allelic specific expression at the germline level. I1307K overexpression is not selected for during tumor progression. No significant financial relationships to disclose.
KI67 in breast cancer: Correlation between proliferation cellular and other prognostic factors
Authors: Gerson R. , Alban L. , Martínez A. , Villalobos A. , Serrano A. 
Published: August 2020

e22184 Background: Breast cancer (BC) is the most common tumor in Mexican women between 35 to 50 years old. KI67 is a nuclear antigen considered as a proliferation marker with potential prognostic significance in BC survival. Objective: To determine the correlation between KI67 and prognostic factors in BC patients (pts). Methods: Of 340 consecutive BC pts seen from January 2000 to September 2008, pts with invasive BC that have a complete IHC assay determination were analyzed (estrogen receptor [ER], progesterone receptor [PR], HER2, p53, KI67). KI67 was determined by monoclonal antibody MIB-1. Patients ´s clinical characteristics and tumor immunohistochemical factors were registered. Patients were divided into 4 groups according to KI67 levels: 1) KI67 < 5%, 2) 6 to 20%, 3) 21 to 50% and 4) > 51%. Descriptive statistical methods and X2, ANOVA tests were used. Results: 154 pts analyzed, mean age 53.5 ± 12 yrs, range 28 -83, median KI67: 25, (0 - 95%). Group 1: 22 pts (14.3%), Group 2: 52 (33.8%); group 3: 49 (31.8%), group 4: 31 pts (20.1%). Median KI67 by group: 5, 15, 30 70%. Among pts with KI67 > 51% we observed: higher proportion of advanced stages (III-IV) [27.3%, 7.7%, 25.6%, 38.7% (p= 0.027)], positive lymph nodes (59%, 25%, 42.8% 70.9%, [p=0.003]), ER negative (27.3%, 5.8%, 28.4%, 51.7% [p= 0.000]), PR negative (36.4%, 26.9%, 22.5%, 61.3%; [p= 0.003]); P53 +ve (9.1%, 71.1%, 73.4%, 77.4%; [p= 0.028]), angiogenesis [> 15 vessels × field] (31.8%, 21.1%, 24.5%, 54.5%; [p=0.006])), triple negative phenotype (4.5%; 3.8%, 10.2%, 41.9%; [p=0.000]). We do not observe correlation among KI67 status age, tumor size and HER2 (p > 0.05). Conclusions: High cellular proliferation through KI 67 (> 51%) was related to poor prognostic factors in BC. No significant financial relationships to disclose.
Breast cancer in young women less than 30 years from southern India: Study on clinical profile and outcome
Authors: Rejiv R. , Biswajit D. , Neelesh R. , Sridevi V. , Sagar T. G. , Shanta V. 
Published: August 2020

e22196 Background: Breast cancer in young patients have an aggressive behaviour with poorer outcome. The patients are in their reproductive age group and are concerned with fertility issues,pregnancy and lactation. The literature pertaining to patients less than 30 years is limited. Methods: 213 Patients under the age of 30 years with breast cancer were studied for Demographics, clinical presentations, pathological profiles, treatment and survival. The case records were retrospectively analyzed between Jan 1993 - Dec 2003 at Cancer Institute (WIA) Chennai. Results: The mean age of the study population was 28 years and ranged between 17 to 30 years. Early menarche, defined as less than 12 years (17.5 %), Nulliparity (21.1%), first child birth less than 18 years (26.8%) were the major risk factors noted. Family history of breast and ovarian cases were seen in 6.6% of the patients. The Stage distribution included Stage I (1.4%), Stage II (31%), Stage III (49.6) and Stage IV (11%) and unclassifiable (7%). Node positive tumours constituted 158 patients (74.1%). Hormone receptor studies were negative in 62% of the patients. Modified radical mastectomy was performed in 164 (77%) of the patients. Non infiltratring ductal carcinoma histopathology was noted in 13.6%. Surgical and radiocastration was performed in 35.2% and 17% of the cases respectively. Of 201 (94.3%) patients who received chemotherapy anthracycline based chemotherapy was delivered in 30.3%. Recurrence pattern included local, local and distant and distant recuurences in 8.5%, 23.5% and 2.3% respectively. The 5 year over all survival for the evaluable patients was 53.2%. Conclusions: Very young Indian patients less than 30 years constitute a unique subset of breast cancer patients with majority being hormone receptor negative and locally advanced stage at presentation. The over all outcome is inferior compared to older patients with breast cancer. More aggressive adjuvant treatment may help in improving survival. No significant financial relationships to disclose.
Comparison of three methods to detect mutations in the PI3K oncogene in FFPE cancer samples
Authors: Rodgers J. , Murray C. , Leaves N. 
Published: August 2020

e22212 Background: PI3Kinase is an important target for new oncology therapies, since it is central to several cell signalling pathways associated with proliferation and survival. Many pharmaceutical companies have PI3K inhibitors in their drug development pipelines all of which are in early phase trials. Activating mutations in exons 9 and 20 of the PI3KCA oncogene have been observed in a number of important cancer types including: gastrointestinal, breast, liver, lung and genito-urinary cancers. The presence of such mutations may prove useful as companion diagnostic biomarkers for prediction of response to therapy. Methods: Source BioScience (Nottingham, UK) tested three different methods for the detection of PI3K mutations in archival tumour samples, in their CPA and GLP accredited laboratories. Eighty formalin-fixed paraffin-embedded (‘FFPE') samples from histologically confirmed breast cancer samples were tested by the new DxS P13K Mutation Test Kit using real-time PCR, by pyrosequencing (Qiagen), and by conventional bidirectional capillary sequencing. Tumour content was evaluated by pathology review. Results: The results of the comparison showed that the DxS test using rtPCR technology was easy to perform, convenient and robust. The DxS test had a high degree of sensitivity provided there was more than 20% tumour content in the test sample as determined by histology and pathology review. Conclusions: In conclusion, the DxS test is a valuable tool for detecting PI3K mutations in FFPE samples from breast cancer patients. No significant financial relationships to disclose.
Potential diagnostic markers in bronchial fluid of small cell lung cancer (SCLC)
Authors: Carrera Revilla S. , Muñoz A. , Zalacain R. , López-Vivanco G. , Uribarri M. , Simón L. , Calvo B. , Jangi M. , Rubio I. , Ruiz de Lobera A. 
Published: August 2020

e22221 Background: Lung cancer is a major cause of mortality worldwide and overall survival rate has not improved significantly over the past 20 years. An early diagnosis could improve prognosis and survival among these patients. The aim of this study was to identify protein markers obtained from bronchial fluids of SCLC patients which may differ from non-pathological bronchoscopy samples. Methods: We have included 43 patients with SCLC diagnosed using bronchoscope and 49 consecutive patients with non pathological bronchoscopy. Bronquial fluid was obtained from each patient and potential protein markers were studied. After being centrifuged, supernatant proteins were analysed using bidimensional electrophoresis with poliacrilamid gel stained with silver nitrate. Gel was scanned and analysed with Progenesis PG6220 program, which measures intensity of each spot. Resultant intensities in each group of patients (SCLC/non pathological bronchoscopy) were compared using T-Student method. We selected as potential markers those spots with a p value of less than 0.05. We calculated “fold change” of each spot as the ratio between mean intensity in SCLC bronchoscopy samples and non pathological bronchoscopy samples. Results: Optimal bidimensional gels of each sample were obtained. Among 300 comparable spots, 10 of them were expressed with a different intensity in both groups of patients; 6 of these potential markers were over expressed in SCLC samples, whereas 4 of them were underexpressed. The “fold change” of these 10 spots ranges from 1.5 to 8.67. Conclusions: Different protein markers can be detected in bronchial fluid obtained from SCLC samples. Significant differences in expression of these biomarkers were detected between SCLC patients and non pathological bronchoscopy patients. The development of an early diagnostic test using these proteins must be validated in future studies. No significant financial relationships to disclose.
Expression of steroids and HER2-neu receptors in breast tumors associated with BRCA1 gene mutations
Authors: Zarubina N. A. , Petrova V. D. , Sinkina T. V. , Terekhova S. A. , Lazarev A. F. , Boyarskikh U. A. , Pechkovsky E. V. , Mishukova O. V. , Filipenko M. L. 
Published: August 2020

e22223 Background: Hereditary breast carcinomas that are attributable to BRCA1 mutations have their own morphological and immunohistochemical characteristics. This study was aimed to analyze the level of expression of steroids (estrogen and progesterone) and HER2-neu receptors in BRCA1 associated breast cancer. Methods: DNA patterns from 264 patients with hereditary breast cancers (breast cancer diagnosed at the age under 40; bilateral breast cancer; combination of breast and ovarian cancers; 2 and more breast cancers in blood relatives). All the patients were residents of the Altai Territory. BRCA1 gene mutations were registered in 34 patients (12.9%): 5382insC gene mutation - in 28 patients; 300A/C - in 2 patients; 4153del - in 3 patients; 185del - in 1 patient. The frequency of the BRCA1 5382insC allele mutation was 7.3; 300A/C - 0.52; 4153del - 0.26; 185del - 0.83. Immunohistochemical characteristics of BRCA1-associated breast tumors tissue from these patients were investigated. Results: 32 BRCA1-associated breast carcinomas were estrogen receptor- negative; 1 - week positive (H-score 50–100); 1 - moderate positive (H- score 100–200). 33 BRCA1-associated breast carcinomas were progesterone receptor- negative; 1 - positive (H-score 200 and more). HER2-negative were 31 BRCA1-associated breast carcinomas; 2 were week positive (HER2-neu +); 1 - was moderate positive (HER2-neu ++). Conclusion: BRCA1-associated beast carcinomas have been found to be more frequently estrogen receptor-, progesterone receptor-, and HER2- negative. These data show that hereditary breast cancer associated with BRCA1 gene mutations poses poor prognosis. No significant financial relationships to disclose.
Risk and endocrine responsiveness (ER) categories in operated breast cancer (BC) patients (pts) from Tucuman, Argentina
Authors: Holgado S. , Elias de Vacaflor A. , Sanchez Segura M. , Viñuales A. , Audi V. , Raul A. , Vigo G. , Pedruzzi R. , Zarba J. J. 
Published: August 2020

e22224 Background: BC is the most common malignancy and the 1st cause of death by cancer in women in Tucuman, Argentina.The expression of hormone receptors and Her 2 neu in tumor tissue with other microscopic variables have shown to be indicators of prognosis and is also useful in therapeutic decisions.The molecular basis for treatment selection is actually the best way for a treatment “target” identification.The objective of this trial was to determine the patients profile in the population with BC under program (all pts studied under methodologic norms of a BC Detection Program) from Tucumán Argentina, defined by risk categories (high, intermediate or low) and endocrine response (high, incomplete or no response)according St Gallen 2007. Methods: The population included in the study were 246 pts with BC from public and private institutions in the province of Tucumán.HE routine biopsies were used for the assessment of histological type and subtype, tumor grade (according to Elston et al. and Nottinghan breast cancer grading method), axillary nodes status, tumor size, and the IHC staining for estrogen, progesterone receptors and Her2 neu.The results were studied grouping and evaluating the data for risk and endocrine responsiveness.The statistic applied was the exploratory analysis.IHC methods were validated with external and internal controls, in 7 cases Her2 was determined also by Fish. Results: 217/246 pts completed all parameters and were classified on risk categories: high (60 patients- 27,6%-); intermediate (156 patients-71,9%-) and low (1 patient-0,5%).No significant differences were found between the ages of groups with different levels of risk.The ER of the pts(n:242/246) showed highly endocrine responsive in 109/242 (45%), incompletely endocrine responsive in 49/242 (20,2%), endocrine no responsive 84/242 (34,7%). and association between endocrine levels of response and age range and tumor size (p <0001 chi-square test and p<0,017). Conclusions: These results are comparable with international data and allows us to know the patients profiles in our population under BC program. No significant financial relationships to disclose.
The impact of genetic factors in the development of thrombosis in cancer patients
Authors: Özkan M. , Koçyigit I. , Dikilitas M. , Özkul Y. , Sari I. , Karaca H. , Emirogullari F. , Eser B. , Er O. , Unal A. 
Published: August 2020

e22227 Background: Thromboembolism is frequent in patients with cancer. Although it is known that several acquired factors take place in this process, the role of the genetic factors is controversial. In this study we analysed the most common genetic polymorphisms which have a role in the development of thrombosis. Methods: Study population consists of 292 (158 with thrombosis and 134 without thrombosis) patients treated between 2004 and 2008. Thrombosis was diagnosed by clinically and radiological measures in any time during the course of disease. Factor V Leiden G1691A, Prothrombin G20210A, Methlene Tetra Hydrofolate Reductase (MTHFR) C677T and Plazminogen Activator Inhibitor (PAI-1) 4G/5G were analysed with PCR-RFLP (Polymerase Chain Reaction- Restriction Fragment Length Polymorphism). Results: In the study group 48 and 1 patient had heterozygot and homozygot polymorphism for Factor V Leiden G1691A respectively. In the control group 32 heterozygot and 1 homozygot polymorphism and there was no statistically significant differents between study and control group (p=0,462).For Protrombin G20210A 11 and 4 heterozygot polymorphism were observed in control and study group respectively. While there was 1 homozygot polymorphism in study group there was no in control group and the difference between two groups was not statistically significant (p=0,198). For MTHFR C677T, 48 and 24 heterozygot polymorphism, 15 and 12 homozygot polymorphism were observed in study and control group respectively. The difference between two groups were statistically significant (p=0,04). There was no statistically significant difference between two groups for PAI-1 4G/5G polymorphisms (p=0,362). In subgroup analyses, statistically significant difference was found only in MTHFR C677T polymorphism in patients with GI cancer and with and without thrombosis (p=0,028). Conclusions: The studies investigating the relationship between genetic factors and thrombosis revealed controversial results. However, we found no genetic factor relevant to thrombosis other than MTHFR C677T polymorphism. Further studies investigating genetic and acquired factors in the development of the thrombosis in detail are warranted for documenting clearly the role of genetic polymorphisms. No significant financial relationships to disclose.
Identification and characterization of SP cells in human lung adenocarcinoma SPC-A1 cells
Authors: Zhu Y. , Chen L. 
Published: August 2020

e22230 Background: There has been an increasing interest in recent years in the role stem cells play in health and disease. With an extensive understanding of their biology, a major role for stem cells in the malignant process has been proposed and the existence of cancer stem cells(CSCs) has been confirmed in hematopoietic malignancies, brain cancer, and solid organ malignancies including breast, prostate, colon, and pancreatic cancer. Lung cancer is the leading cause of cancer mortality in most large cities of China. It is possible that lung cancer contains cancer stem cells responsible for its malignancy. The aim of this study is to identify, characterize and enrich the CSC population that drives and maintains lung adenocarcinoma growth and metastasis. Methods: Side population (SP) cell analysis and sorting were applied to established human lung adenocarcinoma cell line and an attempt to further enrich them by preliminary serum-free culture before fluorescence activated cell sorting(FACS) was done. Stem cell properties of SP cells were evaluated by their proliferative index, colony-forming efficiency, tumorigenic potential, bi-differentiation capacity and the expression of common stem cell surface markers. Results: Lung cancer cells could grow in a serum-free Medium (SFM) as non-adherent spheres similar to neurospheres or mammospheres. The proportion of SP cells in cell spheres was significantly higher than that in cells grown as monolayers. SP cells had a greater proliferative index, a higher colony-forming efficiency and a greater ability to form tumor in vivo. SP cells were both CCA positive and SP-C positive while non-SP cells were only SP-C positive. Flow cytometric analysis of cell phenotyping showed that SP cells expressed CD133 and CD44, the common cell surface markers of cancer stem cells, while non-SP cells only expressed CD44. Conclusions: SP cells existed in human lung adenocarcinoma cell lines and they could be further enriched by preliminary serum-free culture before FACS sorting. SP cells possessed the properties of cancer stem cells. No significant financial relationships to disclose.
Low frequency of RAS and absence of FLT3-ITD gene mutations in patients with Myelodysplastic Syndromes in India: AIIMS experience
Authors: Chaubey R. , Sazawal S. , Mahapatra M. , Saxena R. 
Published: August 2020

e22231 Background: Chromosomal abnormalities and molecular detection has potential importance for diagnosis and prognosis of MDS, although the mechanisms underlying the development of MDS and their progressive evolution to AML are still largely unknown. Since, no studies have been reported from India on the prevalence of N-RAS, K- RAS point mutation in codon 12 and FLT3-ITD mutations in patients with MDS, we undertook this study. Methods: DNA and RNA were extracted from bone marrow /peripheral blood. Using RT-PCR the patients were screened for length mutations in FLT3 gene. PCR-RFLP and nested PCR-RFLP were used for the detection of point mutation in codon 12 of N-RAS and K-RAS. Results: A total of 53 patients (median age 39 yrs, range 9–78yrs; M: F 2:1; median TLC-3.9×109/l, range 0.8–116 ×109/l Median platelet count- 87 ×109/l, range 1–349 ×109/l, Median hemoglobin -6.8 g/dl, range 2.7- 16.1 g/dl, were studied. One out of 53 patients (2%) was found positive for N-RAS and four patients were positive for K-RAS (8%) mutation. FLT3-ITD mutation was studied in 47 patients; all the patients were found negative. The mean observation of all the patients was 30 months and the median overall survival was 28 months. Nine patients died during follow up. The presence of N-RAS codon 12 mutation was associated with the poor survival. FLT3-ITD mutation was not observed in any of our cases, which is in contrast to 3% reported from the West. Conclusions: Thus, it appears that the RAS and FLT3 mutations are uncommon in MDS patients in India. No significant financial relationships to disclose.