tbuckley/cabot-search huggingface dataset:
Comparative proteome analysis of gonadal and extragonadal germ cell tumors
Authors: F. Honecker, S. Glaesener, T. Rohlfing, T. H. Brummendorf, C. Bokemeyer, S. Balabanov
Journal: Journal of Clinical Oncology (2006)

14530 Background: Germ cell tumors (GCTs) are the most common malignancy in young Caucasian males aged 20–40. Even though highly effective treatment strategies have been developed for the majority of patients (pts) with GCT, long term survival rate in pts with primary mediastinal non-seminomas nowadays remains below 50%. The molecular mechanism underlying the increased resistance to treatment remains elusive. Therefore, a systematic approach of global proteome analysis was used as a screening tool to compare GCT cell lines of gonadal and extragonadal origin. Methods: Comparative protein expression analysis of two GCT cell lines, NTERA2 (of gonadal origin) and NCCIT (of mediastinal origin) was performed using 2-dimensional gelelectrophoresis. Differentially expressed proteins were analyzed using matrix-assisted laser desorption/ionization - time of flight mass spectrometry (MALDI-TOF). Identification of proteins was performed using peptide mass-fingerprinting and NCBI/SwissProt database search. Results: On average, 761 spots on each gel were detected. Of these, 66 proteins were found to be differentially expressed in an at least in 2-fold manner. Expression of 47 proteins was found to be higher in NCCIT than in NTERA2, 19 proteins showed lower expression in NCCIT than in NTERA2. All 66 spots were analyzed, and 35 (51%) proteins were positively identified by peptid mass fingerprinting and database search. These proteins could be grouped into different categories: 9 are involved in metabolism, 5 each in protein folding and DNA-binding/transcription, 4 in cytoskeleton/cell movement, 3 in cell signaling/differentiation, and 1 each in ion transport and membrane/vesicle trafficking. Of 7 proteins, the function is currently unknown. Conclusions: This analysis demonstrates that proteomic tools are valuable in studying similarities and differences between gonadal and primary extragonadal GCTs. Further characterization and functional analysis of selected proteins is ongoing, with special emphasis on factors potentially involved in treatment resistance and sensitivity. Furthermore, the acquired proteome map of untreated cells will help to identify cellular changes occuring under different experimental conditions in vitro like induction of differentiation and response to cytotoxic treatment. No significant financial relationships to disclose.
IFCT0401 trial: Phase II study of gefitinib administered as first line treatment in non-resectable, pneumonic-type adenocarcinoma (P-ADC)
Authors: J. Cadranel, E. Quoix, P. Debove, D. Moro-Sibilot, J. M. Brãchot, P. J. Souquet, J. C. Soria, F. Morin, B. Milleron
Journal: Journal of Clinical Oncology (2006)

7186 Background: P-ADC is a peripheral lung ADC with a pneumonic radiological presentation, most often containing the bronchioloalveolar carcinoma variant in the 2004 classification. In this setting, EGF receptor tyrosine kinase inhibitors have shown promise. We therefore conducted a prospective multicentric phase II trial to evaluate gefitinib (G) (250 mg/d) as first line treatment in non-resectable P-ADC. Methods: Inclusion criteria: previously untreated, non-resectable cyto/pathologically proven P-ADC with &gt; 3-month expected survival. Primary objective: disease control rate (DCR) - objective response (OR) plus stable disease (SD) for 3 months. Secondary objectives: tolerance, quality-of-life, time-to-progression (TTP), survival, and identification of clinical, pathological and biological markers associated with DC. Results: From 04/04 to 06/05, 88/90 enrolled patients were eligible. All had stage IV disease, with pulmonary (n = 86) and/or extra-thoracic metastasis (n = 10). After review by the clinical trial panel 85/88 were evaluable for response. Tissue-biopsies were collected for central pathological review and molecular analyses. Patients: all Caucasians, median age 64 yrs (27–84), PS &lt;2 in 80.7%, 48 females (54.5%), 33 never (38.6%), 49 former, and 5 current smokers. At 3 months, DC was achieved in 25/85 patients (DCR: 29.4%, CI = [20–39]), including 11 OR (13%, CI = [6–20]) and 14 with SD (16.5% CI = [9–24]). The longest duration of OR is 19.5+ months (4+ to 19.5+) and SD 18+ (5 to 18+). Median TTP is 2.9 months (CI = [2.5–3.3]) but median survival time was not achieved after a 12-month follow-up median time. No death-related toxicity was observed. Only 1 patient stopped G because of skin toxicity (GIII). DC was associated with female gender (p = 0.095, and 0.002 for OR), non-mucinous tumor (p &lt; 0.001, and 0.006 for OR) and absence of rales (p = 0.009) but not with smoking (except for OR, p = 0.024), PS, bronchorrhea, hypoxemia, extra-thoracic metastasis, or Tx presentation. Conclusions: Gefitinib is active and well-tolerated as first-line treatment of non-resectable P-ADC in a Caucasian population, with a 13% OR rate and a 30% DCR. Interestingly, DC was maintained on a long term under G, maybe resulting in improved survival time. [Table: see text]
Absence of racial predilection for aggressive tumor phenotype among low socio-economic status women with breast cancer
Authors: K. A. Dookeran, Y. Wang, X. Gao, K. Ferrer, M. Sekosan, R. DeLaTorre, E. Radeke, W. McCaskill-Stevens, H. Zaren
Journal: Journal of Clinical Oncology (2007)

10554 Background: Survival disparity for African-American (AA) women with breast cancer has been associated with more frequent aggressive tumor phenotype, manifested as higher stage, high grade and negative estrogen/progesterone receptor (ER/PR) status. However, AAs more often have low socioeconomic status (SES), and other studies suggest that low SES, not simply race, is associated with these prognostic features. We hypothesized that low SES AAs and non-AAs with breast cancer would demonstrate similar aggressive tumor phenotype and prognosis. Methods: Variables were analyzed for 538 consecutive low SES women treated between 1/00–12/05. Comparison between racial groups was done with independent t-test &amp; Chi-square test. Associations were examined with logistic-regression, and compared as odds ratios (OR) &amp; 95% confidence intervals (CI). Survival was computed using Log-rank test &amp; Kaplan-Meier method. Results: At median follow-up of 32 months, there were 335 AAs &amp; 203 non-AAs. No significant differences occurred between racial groups for tumor size &amp; grade, node status, stage, ER/PR status, and frequency of survival events. HER2+ status was more frequent in non-AAs (25.1% vs. 17.9% AAs; p=0.048). No significant differences occurred between races for treatment with surgery, chemo &amp; endocrine therapy, however radiation was more common in non-AAs (73.4% vs. 62.2% AAs; p=0.012) but AAs were significantly older (p=0.0001) and had more comorbid disease (p=0.0001). See Table for prevalence of aggressive tumor features. Age-adjusted logistic-regression showed no racial predilection for negative ER/PR, high grade and higher stage, but AAs were less likely to be HER2+ (OR=0.644; 95% CI=0.415–1.00; p=0.05). Log-rank tests showed no differences between racial groups for age &amp; stage-specific disease-free &amp; overall survival. Conclusions: These results confirm that among similar low SES women with breast cancer, there is no racial predilection for aggressive tumor phenotype and poor prognosis. [Table: see text] No significant financial relationships to disclose.
Whole cell preparations of MCF-7 breast carcinoma cells are more active than lysed cell preparations in lymphocyte blastogenesis assays (LBAs) of breast cancer patients
Authors: K. Hsu, J. F. Head, X. Jiang, R. L. Elliott
Journal: Journal of Clinical Oncology (2004)

2596 Background: We have previously reported that whole cell preparations of breast carcinoma cells from either an autologous or allogeneic source (MCF-7 cells) could produce immune responses, increased lymphocyte proliferation in a LBA, in breast cancer patients vaccinated with tumor cells, tumor antigens and two biological adjuvants (IL-2 and GM-CSF). We also showed that after vaccination with the tumor antigens (CEA, CA 15–3 and CA125), there were significant increases in the proliferation of the breast cancer patients' lymphocytes in response to the antigens in the LBA. The present study was undertaken to determine if tumor cell lysates would be more antigenic than the whole cell preparations. Methods: MCF-7 cells were lysed by two cycles of freeze thawing and a sample was tested in cell culture for viability. The lysate was then tested in LBAs and the results compared to those from whole cell preparations of MCF-7 cells (detached from cell culture plate, allowed to regenerate surface antigens while being agitated, and treated with mitomycin C to prevent further proliferation). Results: We found that there was significantly less activity in the lysate (38% to 81% less) than the whole cell preparation in 6 of the LBAs from 9 breast cancer patients. However, the lysate was much more active in 2 of the patients' LBAs (280% and 350% increases). One patient showed no difference between the two preparations. Conclusions: Whole cell preparations of allogeneic MCF-7 cells have immunologic activity in more breast cancer patients than cell lysates, as determined by LBAs. However, a small but significant proportion (20 to 25%) of patients have a significantly greater immunologic response to the cell lysate. Further investigation of the pre-vaccine LBA activity of the whole cell and cell lysate as they relate to immunologic response to our breast cancer vaccine is warranted to determine if the cell lysate should be added to the vaccine. No significant financial relationships to disclose.
Abstract 15382: The Value of Prehospital and Inhospital High-Sensitivity Troponin T Analysis for Rapid Rule in and Rule out of Patients with Acute Myocardial Infarction
Authors: Carsten Stengaard, Jacob Thorsted Sørensen, Søren Ladefoged, Erika Frischknecht Christensen, Jens Flensted Lassen, Hans Erik Bøtker, Christian Juhl Terkelsen, Kristian Thygesen
Journal: Circulation (2012)
14–3-3 σ and checkpoint with forkhead and ring finger (CHFR) methylation in serum in erlotinib-treated non-small-cell lung cancer (NSCLC) patients (p) with EGFR mutations
Authors: N. Reguart, R. Porta, M. Provencio, F. Cardenal, M. Cuello, J. L. Ramirez, C. Mayo, P. Lianes, M. Taron, R. Rosell
Journal: Journal of Clinical Oncology (2007)

7600 Background: 14–3-3 proteins have 130 potential binding partners, including Cbl. 14–3-3 expression can prevent mutant EGFR binding to Cbl, impairing ubiquitination and endocytosis. 14–3-3s is frequently methylated in NSCLC; we hypothesized that in the presence of EGFR mutations, methylated 14–3-3s could permit the formation of the EGFR-Cbl complex. CHFR is a checkpoint that delays entry into metaphase in response to mitotic stress. Methods: 73 stage IV NSCLC p with EGFR exon 19 deletion or exon 21 L858R mutation received first- or second-line erlotinib single therapy. 14–3-3s and CHFR methylation was examined in the baseline serum of these p. Results: Median age, 63 (range, 26–83); females, 48 p (65.8%); Caucasian, 72 p, Asian, 1 p; never-smokers, 45 p, ex-smokers, 21 p, smokers, 7 p; adenocarcinoma, 64 p, large cell carcinoma, 9. PS: 0, 19 p, 1, 42 p, 2–3, 12 p. 14–3-3s was methylated in 39.7% and CHFR in 42.5% of p. No differences in p characteristics were observed according to methylation status. Complete response was observed in 11.1% of p, and partial response in 75.4%. Overall response was 86.5%. There was a trend toward a higher response rate in p with unmethylated CHFR (94.4% vs 76.6%; P=ns). Overall median time to progression (TTP) and survival (MS) have not been reached either in first- or second-line. However, when split according to methylation status, there was a trend toward better TTP and MS in both first- and second-line in p with methylated 14–3-3s. TTP in second-line in p with methylated 14–3-3s has not been reached, while it was 10.8 months (m) for p with unmethylated 14–3-3s (P=ns). TTP in second-line in p with methylated CHFR was 5.2 m but was not reached for p with unmethylated CHFR (P=0.05). Conclusions: Methylated 14–3-3s can permit Cbl binding to mutant EGFR and predict longer-lasting response to erlotinib in p with EGFR mutations. The precise role of CHFR warrants further research. Complete data will be presented. No significant financial relationships to disclose.
A phase II study of two induction schedules of high dose carboplatin (HDC) vs weekly paclitaxel/gemcitabine (WPG) followed by paclitaxel/carboplatin/gemcitabine (PCG) in advanced ovarian cancer (AOC)
Authors: G. Bolis, G. Polverino, C. Sciatta, G. Scarfone, G. Scambia
Journal: Journal of Clinical Oncology (2006)

15062 Background: Patients (pts) with newly diagnosed AOC generally receive platinum plus taxane therapy. G represents a new active agent to improve the standard regimen. To investigate the safety of two schedules of induction treatments both followed by triplet PCG we have drafted a phase II study. Methods: 14 pts, suboptimally debulked (FIGO stage IIIc) entered the study. HDC ( AUC 7,5) was administered for 2 courses every 21 days ( arm A) and P ( 80 mg/sqm, d 1,8,15,22) + G ( 2500 mg/sqm, d 1,15) (arm B). Both regimens have been followed by standard triplet P ( 175 mg/sqm, d1) + C ( AUC 5, d1) + G ( 800 mg/sqm, d1,8) every 21 days for a total of 6 courses. Antiemetics, corticoids, antihistaminics and ranitidine have been added. Results: The median age was 57 y (39–68). Histology was serous in 64.3%, mixed 14.3% and other 21.4%. All pts had Grade 3 tumor but one. Seven pts received arm A schedule and 7 arm B both followed by PCG regimen. Worst haematological toxicities ( in term of nadir) observed in all courses for all pts were neutropenia G4 ( 42.8% arm A vs 71.4% arm B), anemia G2 (71.4% arm A vs 57.1% arm B), thrombocytopenia G2 ( 57.1% arm A vs 42.8% arm B). Most common non haematological toxicities were alopecia and mild nausea/vomiting. Mild paresthesias in both regimens were observed. No sepsis or neutropenic fever nor unespected toxicity or treatment-related deaths were observed. 71.4% of pts completed foreseen schedules of treatments. 78.5% of pts received erytropoietin and 28.5% G-CSF support. Conclusions: HDC and weekly PG followed by triplet PCG are feasible and safety regimens in AOC pts ( residual disease &gt; 1 cm). Further phase II-III setting study using these schedules will be conducted. No significant financial relationships to disclose.
Effect of glucocorticoid receptor on prostate development and cell proliferation in prostate gland
Authors: Irina Budunova, Takashi Matsumoto, Alexander Yemelyanov, Ya Juan Yao
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

4303 

Glucocorticoid hormones have a variety of important functions in eucaryotic cells and tissues; they usually promote cell differentiation and inhibit proliferation. It is known that glucocorticoids have an inhibitory effect on androgen-independent prostate carcinoma (PC) cell growth in vitro and in vivo. The glucocorticoid control of cellular functions is mediated via glucocorticoid receptor (GR), a well-known transcription factor. In this work we characterized the effect of GR on prostate development and prostate cell proliferation in transgenic mice overexpressing GR in basal epithelial cells of prostate. To quantitatively characterize the mouse prostate morphology we performed the analysis of the luminal bridging that reflects the complexity of prostate gland. We found that in both lobes of prostate of adult K5.GR transgenic males the luminal bridging was significantly decreased. In dorsolateral prostate of K5.GR mice the number of glands with luminal bridging was three times lower than in prostate of w.t. littermates. In ventral mouse prostate the luminal bridging is more common finding. Thus, we have compared the average number of luminal bridging /gland, and found that the luminal bridging was more than 2.5 times decreased in K5.GR transgenics in comparison with w.t. littermates. In addition, we have evaluated the proliferation rate in prostate glands using BrdU immunostaining. We found the statistically significant two-fold decrease of the number of BrdU-positive cells in both lobes of prostate glands in K5.GR-transgenic mice. These data indicate that GR plays an important role in regulation of prostate development and proliferation.
The effect of treatment on the bone mass in patients with Hodgkin's disease (hd)
Authors: I. Chmielarczyk-Koszykowska, J. Pawlega
Journal: Journal of Clinical Oncology (2004)

8220 Background: According to the available literature, bone destruction as a sequel of Hodgkin's disease treatment is very rare reported. Methods: In order to assess the associations between therapeutic methods employed in HD and bone mass, patients with HD and the controls were subjected to a densitometric examination (DEXA). In some patients with available radiological records (80% of the entire group), morphometric measurements of the pectoral vertebrae and the analysis of radiograms in search for eventually fractures were performed. The study group consisted of 49 HD patients (26 women and 23 men in average age 46 years), while the controls included 98 individuals randomly selected from the general population and matched for age, sex and body mass index. Bone mass was estimated in g/cm3 as the mean value for the patients and the controls. The differences between the mean values were tested by the Student's t test, with p<0.05 accepted as the level of significance. Results: Females with HD showed a significant decrease of bone mass, especially after subdiaphragmatic radiotherapy. A correlation was detected between the decrease of bone mass and iatrogenic menopause. In HD male patients, an increase in bone mass was demonstrated, regardless of the therapeutic method employed. Morphometric measurements of the available radiograms originating from patients with HD confirmed the presence of imminent or complete fractures in over 90% of the patients, regardless of their sex, age and the therapeutic methods. Conclusions: Female patients treated for HD should be subjected to densitometry after treatment and prevention of bone fractures by biphosphonates and hormone replacement therapy should be considered. The increase of bone mass among men with HD requires future investigations. No significant financial relationships to disclose.
Quantification of a panel of prognostic markers gives a novel method for predicting radiosensitivity in head and neck squamous cell carcinoma cell lines
Authors: K. B. Roberg, L. Farnebo, L. Norberg-Spaak
Journal: Journal of Clinical Oncology (2007)

6082 Background: The present study was undertaken to evaluate the possibility of using the expression of a panel of proteins involved in apoptosis and/or growth control as predictive markers for radiotherapy response. Methods: Nine head and neck squamous cell carcinoma (HNSCC) cell lines were selected to represent different parts of the spectrum of in vitro radiosensitivity. These cell lines have an intrinsic radiosensitivity (IR) between 1.4 and 2.6 measured with a 96 well plate clonogenic assay. Results: Fourteen proteins e.g. Bcl-2, Bcl-X L , Bax, Bad, Bak, Puma, survivin, COX-2, Hsp70, MDM2, p53, EGFR, cyklin D1 and SMAD4 were investigated in above mentioned cell lines and in normal oral keratinocytes (NOK). Each protein was quantified using Western blot analyse and the relative densiometric value from each blot was adjusted for actin and standardized to NOK. The correlation between each protein and IR was analyzed but none significant correlation was found. When combine different proteins, EGFR, Survivin, Bcl-2, Bak, Hsp70 and Smad4 together show the highest significant correlation to the IR. As Western blot is a semi quantitative method we decided that a division into groups depending on the level of protein expression would give a more realistic description of the prognostic value of the detected changes The protein expression was classified into four groups (0–4 point; no, small, middle or large changes compared to NOK) and each p53 mutation got one point. We named this grouping Number of Negative Points (NNP). The NNP for all 15 factors together show a significant correlations to IR, R=0.826 and P= 0.006. A multivariate statistical calculation was carried out to select the combination of factors that had the strongest correlation to IR and the best combination was EGFR, survivin and p53 mutations, R=0.935 and P&lt;0.001. Conclusions: Our results show that it is only possible to predict the IR of tumor cells if combinations of prognostic factors can be analysed. Taken together, we here present a novel method that gives the possibility to combine different prognostic factors and which also enhances the chance to predict the radiosensitivity of HNSCC cells. No significant financial relationships to disclose.
Phase II study to evaluate efficacy and safety of irinotecan, capecitabine, and bevacizumab in patients with metastatic colorectal cancer (mCRC).
Authors: P. Garcia Alfonso, M. Chaves, A. Muñoz Martin, A. Salud Salvia, R. Vilchez, A. Yuste, C. Gravalos Castro, B. Queralt Merino, E. Gonzalez Flores, A. Lopez Ladron, F. Losa, A. Oltra Ferrando, M. J. Gomez Reina, J. M. Campos, E. Aranda
Journal: Journal of Clinical Oncology (2011)

e13018 Background: XELIRI regimen (combination of capecitabine and irinotecan) is an active and well tolerated treatment for mCRC. However, data available on the combination of XELIRI regimen with bevacizumab (BVZ) in patients (pts) with mCRC are limited at present. Therefore the aim of this study is to evaluate the efficacy and safety of the biweekly (biw) scheme with XELIRI regimen, plus BVZ in pts with mCRC. Methods: A multicentric, prospective, open-label phase II trial. Treatment scheme: irinotecan (175mg/m2 iv infusion 90 min, day 1, every 2 weeks) + capecitabine (1,000mg/m2 bid oral, days 2-8; pts aged ≥65, max dose: 800mg/m2 bid) + bevacizumab (5mg/kg, iv, day 1, every 2 weeks).Safety results from an interim analysis are presented. Results: A total of 77 pts were evaluated (66.2%, male) with a median age of 65.1 yrs (41.1-81.1). ECOG PS was ≤1 in 96.1% of pts. Primary tumor locations were: colon (51.9%), rectum (31.2%) and rectum/colon (16.9%).Twenty-seven pts (35.1%) received adjuvant chemotherapy. Mean time to primary tumor diagnosis was 16.3±30.3 months. Metastases were detected in liver (63.6%), lung (51.9%), nodes (14.3%), and peritoneum (11.7%). Surgery of metastatic disease was performed in 7.8% of pts. The most frequent grade 3-4 toxicities registered were: diarrhea (15.6%), asthenia (13%) and neutropenia (9.1%). The frequency of occurrence for the most frequently AEs related to BVZ were 2.6% hypertension, 1.3% proteinuria; while for the least frequent AEs: 3.9% intestinal perforation, 6.5% pulmonary embolism, 2.6% thrombosis and 1.3% DVT. A total of 59 pts discontinued the study treatment, being the most common reasons: AEs (16.9%), disease progression (14.3%) and surgery (14.3%). Twelve pts (15.6%) died during the study due to disease progression (7 pts), AEs (4 pts), or unknown reason (1 patient). Three of the 4 AEs causing pts’ death occurred as a result of toxicity (2 cases of multi-organ failure and 1 case of intestinal perforation). Conclusions: These preliminary results show that biw scheme with XELIRI regimen, plus BVZ has a feasible and manageable safety profile for the treatment of pts with mCRC. Further analysis will be necessary to confirm these results.