bluuebunny/crossref_metadata_2025_split huggingface dataset:
Avemar inhibits the growth of mouse and human xenograft mammary carcinomas comparable to endocrine treatments
Authors: Tejeda M. , Gaál D. , Szűcs I. , Telekes A. 
Published: March 2020

21132 Background: An in vitro study demonstrated that Avemar increased the effect of Tamoxifen on MCF7 (ER+) mammary carcinoma cells. Methods: MXT (ER+) mouse mammary tumor tissue was transplanted s.c. into BDF1 mice. The tumor bearing animals were treated p.o. with Avemar. Then the most effective Avemar dose (3.0 g/kg), Tamoxifen (0.5 mg/kg s.c.), Examestane (10 mg/kg i.p.) and Anastrasol (5 mg/kg i.p.) monotherapies and their combinations with Avemar was compared. All treatments were given once daily, for 10 days, starting 7 days after the tumor transplantation. The same experimental schedule was repeated using T47/D (ER+) human breast carcinoma cell lines transplanted into C.B-17/Icr-scid/scid mouse. Finally, the growth of T47/D and MDA-MB-231 (ER-) xenografts treated by Avemar was compared. Tumor volume was measured up to 25 days after transplantation in MXT and 55 days in xenograft. Results: In MXT model all monotherapies and combinations led to retardation of tumor growth. Combination of Avemar with any of the endocrine treatment enhanced the efficacy compared to endocrine monotherapy. Out of the four monotherapies the best result was achieved by Avemar (50% inhibition). The combination of Avemar with Examestane increased the tumor growth inhibition to 60.4% compared to control. The other treatments did not exceed the effect of Avemar monotherapy. In xenograft model Avemar produced 50% tumor growth inhibition compared to control and was more effective than the other treatments Examestane (26%), Anastrasol (25%) or Tamoxifen (42%). Combined treatment with Avemar always improved efficacy within the range of 3–10%. Avemar showed similar efficacy when T47/D (49%) and MDA-MB-231 (52%) xenografts were compared. Conclusions: The tumor growth inhibitory effect of Avemar on ER positive MXT mouse breast carcinoma as well as in T47/D xenograft models are comparable (equal or better) to standard endocrine treatments. Avemar certainly did not reduce the effect of endocrine treatments. The antitumor activity of Avemar did not depend on the estrogen receptor status. No significant financial relationships to disclose.
The effect of surgical resection on serum proteomic profiles in non-small cell lung cancer (NSCLC)
Authors: Alzetani A. , Ward D. G. , Rathinam S. , Starczynski J. , Rajesh P. B. , Martin A. , James N. D. , Johnson P. J. 
Published: March 2020

21143 Background: Surface-enhanced laser desorption/ionisation time-of-flight mass spectrometry (SELDI) was used to detect characteristic serum proteomic profiles that discriminate between Non-small Cell Lung Cancer (NSCLC) and non-cancer controls. The changes in these profiles in response to curative resection were examined to determine if they returned to “normal” as would conventional tumor markers. Methods: Serum samples were collected from 70 patients and 75 controls. Further samples were obtained from 25 of these patients following resection with curative intent. SELDI analyses using CM10 & IMAC ProteinChip arrays were undertaken. The Wilcoxon rank test was used to detect differentially expressed peaks. Results: A preliminary analysis using CM10 on 39 patients, 38 controls, and 17 follow-ups showed 19 differentially expressed peaks (p<0.01) but no evidence of return to normal after treatment. The IMAC chip analysis, on all samples, revealed 40 discriminatory peaks (p<0.01). These data were used to classify patients with a specificity and sensitivity of more than 75%. Some of these cancer associated peaks returned to normal at follow-up. We have identified 10 of the discriminatory proteins. Conclusions: SELDI profiling has detected differentially expressed proteins in the serum of lung cancer patients. Successful treatment resulted in some, but not all, of the discriminatory peaks returning to non-cancer levels. It could be hypothesized there is a tumour specific profile which changes with treatment and a host specific profile that represents the patient's response to the presence of the disease or its inducing factors. No significant financial relationships to disclose.
The effect of antisense oligodeoxynucleotides targeting Aurora A kinase on cell proliferation and chemosensitivity to paclitaxel in human lung cancer cell line A549
Authors: Meng R. , Wu G. , Yang K. Y. , Cheng J. 
Published: March 2020

21147 Background: Aurora kinases representing a family of evolutionarily conserved mitotic serine/threonine kinases have been found elevated in lung andenocarcinoma cell line A549. It is suggested that the overexpression of Aurora A contributes to the carcinogenesis, chromosomal instability (CIN), and de-differentiation of lung cancers. To address its possibility as a therapeutic target for lung cancer, we employed the antisense oligodeoxynucleotide (ASODN) technique to inhibit Aurora A expression and investegate its effect on tumor growth and cell cycle of A549, as well as the chemosensitivity of paclitaxel. Methods: Aurora A ASODN was synthesized and transfected into A549 cells by lipofectAMINE 2000.Aurora A mRNA and protein expression were examined by reverse transcription -polymerase chain reaction (RT-PCR) and Western blot respectively.Cell cycle distribution was observed by flow cytometer.MTT assay was used to evaluate cell inhibition ratio before and after transfection. Results: The proliferation of the A549 cells was inhibited by Aurora A ASODN dose and time dependently. It was also observed that the IC50 of A549 cells after 48 hours’ treatment of ASODN was about 300nmol/L and under such circumstances, the Aurora A mRNA and protein expression significantly decreased (P<0.05), along with the induction of accumulation of cells in S phase and the G2-M transition. Furhermore, cell inhibition ratio of the combination of Aurora A ASODN and paclitaxel was higher significantly than paclitaxel(P<0.05) or Aurora A ASODN alone (P<0.05). Conclusions: Inhibition of Aurora A expression can results in the suppression of cell growth and chemosensitizing activity to paclitaxel in human lung cancer cell line A549. No significant financial relationships to disclose.
Time to recurrence and survival in triple negative early-stage breast cancer
Authors: Gerson R. , Villalobos A. , Alban L. , Serrano A. 
Published: March 2020

21151 Background: Breast cancer (BC) is the most common neoplasm among Mexican women. Clinical, tumoral and biologic factors have proven useful in predicting prognosis regarding recurrence and survival. Triple negative (TN) phenotype (ER, PR and HER2 negative) has been reported to be associated with more aggressive clinical behavior. Objective: To compare clinical, tumor, biologic characteristics of TN time to recurrence and survival to other phenotypes in early BC. Methods: Records of women with stage I - II BC evaluated from Jan. 2000 to June 2006 were reviewed. ER/PR+: > 10 fmol/pgr and HER2+, 3+ by immunohistochemistry or FISH > 2.2 were considered. Five groups were designed: 1) TN, 2) triple positive, 3) HER2-/ER/PR+, 4) HER2+/ER/PR-, 5) HER2-/ one hormonal receptor (HR) +. ANOVA, Chi-2 and Kruskal-Wallis tests were applied for the statistical analysis. Results: 110 patients were included (17, 14, 52, 11, 16 respectively). Median age (43, 49.5, 55, 53 51 yrs); clinical stage; tumor size, axillary lymph node status and angiogenesis score were similar in all groups, p > 0.05. Median Ki67 was higher in TN group (47.5, 20, 20, 42.5, 10, p< 0.000). Proportion of patients with conservative surgery was similar, p= 0.308. Fourteen recurrences were observed, 2 local and 12 systemic (3, 1, 3, 5, 2 in each group). Median time to recurrence (6, 54, 30, 20, 27 mos); there were 7 deaths due to tumor. Number of deaths was higher in TN and HER+/HR- (17.4, 7.1, 0, 18.1, 6.2%). Conclusions: TN phenotype represents 15% in this early BC population and was associated to higher Ki67. There are premature signs (age, number of recurrences and deaths) that suggest a poor prognosis for TN patients, similar to those with HER2+/ERPR- . No significant financial relationships to disclose.
Cancer prevalence in kidney transplant recipients in two general hospitals from Peru
Authors: Beltran B. E. , Morales D. , Medina M. , Espejo J. , Castillo R. , Riva L. , Hurtado de Mendoza F. , Salinas E. , Carrasco A. , Malaga J. 
Published: March 2020

21155 Background: Malignancy following kidney transplantation is an important medical problem during long-term follow-up. The accrual risk is approximately 100 times greater than the general population. We report some features of the cancers developed in our patient population Methods: We retrospectively reviewed records of 1050 kidney transplant recipients who received both unrelated or related allograft transplants from January 1972 to April 2006 and recorded the incidence of de novo malignancies that developed in this cohort. The study was carried out in two centers in Peru. The statistical method was descriptive and parametrical. Survival was calculated using the Kaplan-Meier method. Results: Forty-six cancer were diagnosed in 42 recipients (4.3%). Twenty six were men and 16 women, mean age was 46.0 years old (range:17–67). Malignancy was diagnosed between 2 to 240 months after transplantation. The tumors included Kaposi's sarcoma (KS) in ten patients, squamous cell carcinoma (SCC) in seven, basal cell carcinoma (BCC) in six, cervix cancer in four, colon and breast cancer in three and hepatocarcinoma in two. Also they were reported one case of small intestine cancer, osteosarcoma, pancreatic cancer, lung cancer, bladder cancer, schwanoma, melanoma, tongue cancer, postransplant lymphoproliferative disease, pelvis renal cancer and carcinomatosis from unknown primary. Thus, KS was the most common malignancy encountered in our series, with a prevalence of 0.95%, followed by SCC observed in 0.66% and BCC found in 0.57% of the patients. The average latency period between transplantation and development of malignancy was 25 months for KS, 72.0 months for SCC and 36.0 months for BCC. KS occurred earlier compared with the other cancers ( P < 0.05); We failed to demonstrate any correlation between age/sex and specific type of cancer. The 10 year - survival was 71%. Conclusions: The prevalence of cancer in our renal transplant recipients was 4.3%. KS and non melanoma skin cancer were the most frequent cancer. Low incidence of postransplant lymphoproliferative disease was found. No significant financial relationships to disclose.
Outcome of patients with locally advanced breast cancer (LABC) followed at the University of Cincinnati (UC)
Authors: Komrokji R. S. , Nahleh Z. , Dhaliwal S. , Sivasubramaniam D. 
Published: March 2020

21160 Background: LABC poses a difficult clinical challenge . The correlation of complete clinical (cCR) and pathological response rates (pCR) based on molecular tumor characteristics with outcome is of great clinical interest. Methods: We conducted a retrospective chart review on consecutive patients diagnosed with LABC who completed NC between 2001–2006 at UC. Pathological response was classified as pCR (no invasive tumor in breast and axillary lymph nodes), RDLN (disease in lymph nodes), RDB( disease in breast), and RDBLN (disease in both). Overall survival (OS)and event free survival (EFS) were calculated using Kaplan-Meier analysis. Result: We included 45 patients. Median age 51, 40% (n=18) white and 60% (n=27) African American, Stage IIB 9%, IIIA 29%, IIIB 51 % and IIIC 11%. 75 % invasive ductal, 9% invasive lobular and 16% inflammatory breast cancer (IBC). ER+/or PR+ in 47% (18% ER + / PR +, 27% ER +/PR -, 2% ER-/PR+), and 53% ER -/PR-. HER2 neu + ( IHC 3 + or FISH ratio > 2.2) was identified in 27% of patients. NC regimens included: doxorubicin or epirubicine plus taxane (paclitaxel or docetaxel) 80 %, anthracycline only 10%, single agent taxane 4%, and 6% other regimens (2 CMF, 1 capecitabine). One patient received NC with trastuzumab. Response to NC was as follows: Clinically, 55% (n=25) achieved cCR, 38% partial clinical response, 4% stable disease and 2% progressive disease. Pathpogically, pCR was achieved in 22% (n=10) of all patients, 7% pPRLN, 24% pPRB and 47% RDBLN . None of the patients with IBC had pCR. Among ER+ and or PR + tumors , 19% achieved pCR compared to pCR of 25% among ER-/PR-. Among HER2 neu +, 17% achieved pCR compared to 25% in HER2 neu -. Among all patients who achieved cCR, only 36% actually had pCR. For patients who did not achieve pCR, OS and EFS were 5.7 years and 19 months respectively compared to both not yet reached for those with pCR. Conclusion: LABC has poor prognosis overall using standard chemotherapy. Clinical response followingNC was not well predictive of pathological response. ER-/PR - tumors respond better to neoadjuvant chemotherapy compared to ER+/orPR+ tumors. Less than 20% of HER2 neu + tumors achieve pCR before trastuzumab's routine use. More research is urgently needed to optimize treatment strategies and improve outcome of LABC and IBC. No significant financial relationships to disclose.
Multi-clinical laboratory validation of a gene expression-based tissue of origin test applied to poorly differentiated and undifferentiated cancers
Authors: Monzon F. A. , Dumur C. I. , Lyons-Weiler M. , Sciulli C. M. , Price M. , Buturovic L. , Becker S. , Rigl C. T. , Anderson G. G. 
Published: March 2020

21161 Background: This multi-clinical laboratory validation assessed the accuracy, reproducibility and robustness of the Pathwork™ Tissue of Origin Test. We focused on tumor specimens that are poorly differentiated to undifferentiated (G3-G4; high grade) because this type of specimen can consume a disproportionate amount of physician time and diagnostic resources. A subset of this type of specimen ultimately will be categorized as cancer of unknown primary (CUP), which comprises 4–5% of all malignancies. The Test uses proprietary analytics and a companion genomic microarray (Pathchip™) to compare expression levels of poorly differentiated to undifferentiated specimens with 15 types of cancer. Test development involved over 2000 specimens from 14 labs, representing 15 cancers and sixty morphologies. Methods: The studies addressed operability limits, specimen stability, potential interferences and reproducibility, as well as validation in molecular diagnostics and commercial laboratories. In all, over 700 frozen tumor specimens and microarrays were analyzed. Results: Clinical validation data demonstrated that the percent agreement of the Tissue of Origin Test was 88% across all tissue types. Between-lab concordance was 95%. If the quantitative result (Similarity Score) exceeded the recommended threshold, the probability that the indicated tissue is present was 95% across all tissue types. If the Similarity Score was less than 5, the probability that the indicated tissue is absent was 98% across all tissues types. Conclusions: The Pathwork™ Tissue of Origin Test, which is under development, is accurate and highly reproducible across laboratories in this study. The test gave consistent results for different tissue handling and extraction methods and has the potential to be an effective aid in the diagnosis of cancer patients presenting with poorly differentiated and undifferentiated tumors. No significant financial relationships to disclose.
Synergistic tumoricidal effect between celecoxib and gabexate mesilate on the human breast cancer cells
Authors: Suh Y. , Chun C. , Song B. , Oh S. , Jung S. 
Published: March 2020

21179 Background: Selective cyclooxygenase 2 (COX2) inhibitors, including celecoxib, has shown its antitumor effects against various cancers including breast cancer. Gabexate mesilate (GM) can be found to have anti-cancer activities against tumors such as colon cancer. We tried to determine whether synergism can exist between GM and celecoxib against human breast cancer cells. Methods: MCF7/Her18 (estrogen receptor positive) and MDA-MB-436 (estrogen receptor negative) human breast cancer cells were used. Celecoxib and GM were added into the culture media at a dose of 30 and 50 μM for estrogen receptor (ER) (+) cells and 50 and 75 μM for ER (-) cells. Cellular proliferation assays wer performed and trypan blue exclusion method was adopted to count the viable cells after culture. Cell cycle analysis and fluorescein-assorted cell sortings were done to check the cell cycle changes after treatment. Immunoblotting using Akt, phosphorylated Akt (p- Akt), β-catenin, COX2 and VEGF was done to evaluate changes in expression of these proteins. Results: Combination treatment group showed significantly enhanced tumoricidal effect than either mono-treatment group on cellular proliferation study. Combined treatment yielded more G1 phase population and G2-M phase cells. (p<0.05) The level of Akt, p-Akt, VEGF, COX2 expression were decreased more significantly than either mono-treatment group. (p<0.05) Conclusions: We think that there could be synergistic effect between GM and celecoxib on the human breast cancer cells. Either drug has been used for many cases without significant problem, and can be tried for further ex vivo studies to determine synergistic effects between them. Possible antiangiogenentic actions after the combination should be evaluated thoroughly in other cell lines to get more preclinical data. No significant financial relationships to disclose.
Correlation between expression of p53, EGFR, cell proliferation defined by Ki67, and survival in stage III/IV non-small cell lung cancer (NSCLC)
Authors: Malika G. B. , Bouzid K. , R Baba-Ahmed G. , Makhloufi T , Taright S , Amrane R , Hannoun D 
Published: March 2020

21181 Background: The aim of the study was to assess the relation between expression of EGFR, p53, cell proliferation defined by the monoclonal antibody Ki67 and survival of patients with non-small cell lung cancer stage III and IV. Methods: 80 patients were included in this study (male 72 / female 8); the median follow up was 15 months. All tumor samples were formalin-fixed and paraffin-embedded. The expression of p53, EGFR and Ki 67 were assessed with the use of immunohistochemically (IHC). P53 was assessed in 66 cases, EGFR in 73 cases and cell proliferation defined by the monoclonal antibody Ki67 in 63 cases. Results: The expression of p53 was positive in 20 % of cases, EGFR was positive in 58,7 % of cases and cell proliferation in 40 % of cases. Survival was estimated from the date of first cycle of chemotherapy using median survival and the Kaplan-Meier survival analysis method. Conclusion: At this time of the study, there was no relation between expression of p53, EGFR, cell proliferation defined by ki67 and survival. Larger and longer follow-up studies may be needed to determine the prognostic role of expression of those factors in NSCLC. [Table: see text] No significant financial relationships to disclose.
No association between NQO1 polymorphism and breast cancer risk in Siberian population
Authors: Filipenko M. L. , Pechkovsky E. V. , Mishukova O. V. , Lazarev A. F. , Petrova V. D. , Selezneva I. A. , Sinkina T. V. , Dimitriadi J. N. , Zarubina N. A. , Terekhova S. A. 
Published: March 2020

21185 Background: NQO1 is a two-electron reductase, which metabolizes a variety of xenobiotics. This FAD-binding protein forms homodimers and reduces quinones to hydroquinones. This protein's enzymatic activity prevents the one electron reduction of quinones that results in the production of radical species. Mutations in this gene have been associated with tardive dyskinesia (TD), an increased risk of hematotoxicity after exposure to benzene, and susceptibility to various forms of cancer. Genetic polymorphism of NQO1 is a C to T point mutation at base pair 609 of exon 6, which codes for a proline to serine substitution in NQO1 protein. This mutation results in a loss of NQO1 activity. Previously it was reported that wild-type NQO1 increased lung adenocarcinoma risk among male smokers in Taiwan. The association of the P187S polymorphism with breast cancer found in study of two independent populations (one from Tyrol, Austria, and the other from Prague, Czech Republic) (Menzel et al., 2004). Methods: The purpose of this study was to determine whether polymorphism in the NQO1 gene may influence breast cancer risk in Siberian population. The prevalent case-control design was used. The cases were 203 patients with breast cancer. Controls consisted of 182 noncancer outpatients. Genotyping for detecting of NQO1 gene polymorphism was performed using PCR amplification with the primer set of 5'- ACGCTAGCTCTGAACTGATTCTCT -3' and 5'- TTTTCTCCTCATCCTGTACCTCT –3’. The amplified PCR products were digested with HinfI and analyzed using electrophoresis on a 2.5% agarose gel. Results: Compared to subjects having C alleles (genotype CC), odds ratio (chi2=0.04, p=0.84309) were 1.116 (0.376–3.311) for subjects having genotype TT. Conclusions: These results suggest that polymorphic variation P187S of the NQO1 gene has no influence on breast cancer risk in Siberian women. No significant financial relationships to disclose.
Phase I/II dose-escalation trial of amonafide for treatment of advanced solid tumors: Genotyping to optimize dose based on polymorphic metabolism
Authors: Kuhn J. G. , Burris H. A. , Jones S. F. , Hein D. W. , Willcutt N. T. , Greco F. A. , Thompson D. S. , Meluch A. A. , Schwartz R. S. , Brown D. M. 
Published: March 2020

2503 Background: Amonafide (AMF), a synthetic imide derivative of naphthalic acid, is a topoisomerase II inhibitor and is subject to polymorphic metabolism based on acetylation genotype. AMF is extensively metabolized by N-acetyltransferase 2 (NAT2) to N- acetylamonafide (AAMF) which has activity nearly equipotent to AMF. In our phase I evaluation, we observed a correlation between NAT2 genotype, AMF/AAMF pharmacokinetics and toxicity (J Clin Oncol 22 [14S]: 2023, 2004). Patients (pts) with slow (S) acetylator genotype tolerated higher doses than those with rapid/intermediate (R/I) acetylator genotype. The present Phase II portion was designed to prospectively determine the dose of AMF based on NAT2 genotype and focused on selected tumor types. Methods: NAT2 genotyping of genomic DNA from blood samples was done prospectively to determine acetylator status of each pt. AMF was administered IV weekly x 3 q4wk, escalation range 320 to 400 mg/m2 for R/I and 400 to 500 mg/m2 for S acetylators. Primary endpoints: safety, MTD, tumor measurements or sustained decreases in tumor markers. Results: Total 47 pts (21 M/26 F), median 66 yr, PS 0–2, acetylator status R/I (26), S (21) with ovarian (11) or prostate (9), breast (8), colon (4) cancers (CA) and other common tumors refractory to therapy were treated; 30 of 47 pts were dosed based on prospective genotyping. Of these 30 pts, 17 were R/I acetylators: no toxicity at 320 mg/m2 AMF in 7/11 pts and manageable myelosuppresion in 4/11 pts observed days 15–21 of cycle but not dose-limiting (DLT); DLT in 3/6 pts at 400 mg/m2. In the 13 S acetylators: at 400 mg/m2 no DLT in 8 pts; DLT in 2/5 pts treated at 500 mg/m2. Other side effects included nausea/vomiting, fatigue and anemia. Of all 47 pts, biologic activity was seen in 6 pts: 3/9 prostate CA (decreased PSA), 2/11 ovarian CA (decreased CA125) and 1/1 GIST (decreased lymph nodes). Conclusions: MTD determined to be 320 mg/m2 in R/I and 400mg/m2 weekly x 3q 4 weeks in S acetylators, respectively, supporting hypothesis that AMF dosing based on prospective NAT2 genotyping may allow for dose optimization based on drug metabolism and result in better tolerance. Phase II assessments at the MTD dose levels are currently ongoing for prostate cancer. No significant financial relationships to disclose.