tbuckley/cabot-search huggingface dataset:
Downregulation of RIZ1 protein expression in left-sided versus right-sided primary colorectal carcinomas and their distant metastases and the association with NF-B activation
Authors: E. Torlakovic, E. C. Marginean, G. Torlakovic, R. Geyer, H. Neufeld, J. Decoteau
Journal: Journal of Clinical Oncology (2009)

e15112 Background: Activation of NF- B leads to enhanced proliferation and the expression of anti-apoptotic proteins, which are cancer phenotypes. RIZ1 inactivation through various molecular events was linked to increased proliferation, migration induction and apoptosis inhibition in human cancer. RIZ1 frameshift mutations were recently reported to be confined to MSI-H colorectal tumors and proximal tumor origin, while its hypermethylation was not limited to MSI-H tumors. However, RIZ1 protein expression has not been evaluated in colorectal carcinoma. Methods: TMAs included 28 left-sided and 12 right-sided primary colorectal adenocarcinomas, their matched normal mucosa and their respective distant metastases. Left-sided tumors were compared to right-sided tumors for expression of RIZ1 protein and NF- B activation. RIZ1 immunostaining was scored semiquantitatively (0–3+). NF- B activation was determined by IHC detecting nuclear translocation of its p65 subunit in more than 30% tumor nuclei. Discrepant results were defined as score difference of 2. Results: RIZ1 was less expressed in tumors than in benign mucosa (p&lt;0.0001, r=- 0.377, Chi-Square). The difference between primary vs. metastatic carcinoma was not significant. Low RIZ1 was associated with NF- B activation (p&lt;0.0001, Linear-by-Linear). Left-sided primary tumors showed less RIZ1 protein expression than right-sided (p=0.03, Chi-Square). NF- B activation was more frequent in left-sided primary tumors and their respective metastases (35% in right vs. 67% in left; p=0.002, Chi-Square Test). RIZ1 expression and NF- B activation were almost identical in primary and their respective metastatic tumors with only 3 discrepant results for NF- B status and 2 discrepant results in RIZ1 expression. Conclusions: While RIZ1 downregulation in colorectal adenocarcinoma due to RIZ1 mutations appears to be associated with MSI-H and proximal origin, its protein expression appears to be downregulated more often in distal tumors. NF- B activation is strongly associated with lower RIZ1 protein expression in colorectal adenocarcinoma. No significant financial relationships to disclose.
Pharmacokinetics study of 5-day on/2-day off low-dose S-1 administration for non-small cell lung cancer.
Authors: T. Shoji, M. Sonobe, H. Sakai, T. Fujinaga, F. Chen, R. Miyahara, T. Bando, K. Okubo, H. Wada, H. Date
Journal: Journal of Clinical Oncology (2010)

e17512 Background: S-1, an oral fluoropyrimidine is usually used as 4-week administration (80mg/m2/day) followed by 2-week rest. However, the compliance of this drug schedule is not satisfactory because of adverse events such as leucopenia, anorexia, and nausea. To improve the compliance with less adverse effect, 5-day on/2-day off low dose of S-1 were given and its pharmacokinetics were investigated for non small cell lung cancer (NSCLC). Methods: The subjects were 12 NSCLC patients. They were divided into 2 groups. Level 1 group (n=6) was given S-1 25 mg/body and level 2 group (n=6) was given S-1 40 mg/body, twice a day, respectively. All patients were administrated S-1 5-day on/2-day off schedule every week. The serum 5-FU concentration was measured. Results: In serum 5-FU concentration measurement, Cmax was 55.3 ± 21.1 ng/ml and AUC0-9 was 290.2 ± 95.7 ng-hr/ml in level 1, and Cmax was 104.2 ± 33.5 ng/ml, AUC0-9 was 541.9 ± 232.3 ng-hr/ml in level 2, which was comparable with recommended concentration of 5-FU continuous intravenous injection (50-100 ng/ml). The adverse events in both group were grade 1 fatigue (n=1 in each group) and anorexia (n=1 in each group). Conclusions: 5-day on/2-day off low dose (40 mg/body, twice a day) administration of S-1 is feasible with acceptable 5-FU concentration and with less adverse effect for NSCLC. The phase II or III trial using this administration protocol in adjuvant setting for NSCLC is warranted. No significant financial relationships to disclose.
Cervical squamous cell carcinoma of the esophagus-a unique series of limited resection and free jejunal graft interposition after neoadjuvant RCTx in 94 patients
Authors: K. Ott, F. Lordick, M. Feith, H. Bartels, U. Fink, H. J. Stein, M. Molls, E. Biemer, J. Siewert
Journal: Journal of Clinical Oncology (2007)

4572 Background: The treatment of cervical squamous cell carcinoma (SCC) is discussed controversial. A limited resection of the cervical esophagus and reconstruction with a free jejenunal graft interposition using a microsurgical technique has been evaluated in our department. Methods: From 1986–2006 94 patients with the initial staging uT2–4, N any cM0 (75 male, 19 female; age 56+9.6, range: 19–74 years) with cervical SCC of the esophagus were treated with limited esophageal resection and reconstructed with a free jejunal autograft in combination after neoadjuvant RCTx within phase II studies. The median follow up is 23 months (0.1–120). Results: Laryngectomie had to be performed in 13 patients (14%). Recurrent nerve palsy on one side was found in 15/77 (19.5%) and on both sides in 13/77 (17%). Complications occurred in 70 (75%) of the patients, 47% of the patients had more than one complication. Reoperations were necessary in 29 patients (31%). The 30-day mortality was 2/94 (2.1%). Median survival is 29.9 months (1-, 3 and 5-year survival rates: 81%, 43%, 41%). 27/94 (29%) patients showed complete tumor regression (ypT0) after RCTx. Prognostic factors are complete tumor regression (p=0.007), ypT-(p=0.006), the R-category (p=0.018), but not the ypN-category (p=0.06). Neither the occurrence of complications (p=0.57) nor reoperation (p=.89) are associated with survival. The complete resection rate was 76 % (71/94). Median survival is 34.3 months, median recurrence free survival is 21.4 months for the R0 resected patients. 30/71 (42%) had a recurrence (locoregional in 27% (19/71), distant metastases in 10% (7/71) and a combination of both in 6% (4/71). Conclusions: Limited resection of the esophagus and reconstruction by a free jejunal graft after neoadjuvant RCTx is highly sophisticated and complex. Despite a high complication and reoperation rate the results are excellent with a low mortality and a good prognosis. This approach seems to be appropriate for cervical SCC in oncological centers with an infrastructure providing interdisciplinary management. Comparable data for cervical SCC of the esophagus without the inclusion of hypopharyx carcinoma do not exist in literature so far. No significant financial relationships to disclose.
Suicidal behavior in child psychiatric inpatients and outpatients and in nonpatients
Authors: C R Pfeffer, R Plutchik, M S Mizruchi, R Lipkins
Journal: American Journal of Psychiatry (1986)

One hundred one child psychiatric outpatients were assessed using a standard battery of measures to identify factors associated with suicidal behavior. Data on these outpatients were compared to those for psychiatric inpatients and nonpatients previously studied. The frequency of suicidal behavior among the outpatients (24.8%) was less than for a comparable group of inpatients (78.5%) but more than for a comparable group of nonpatients (12%). Four variables--recent general psychopathology, preoccupation with death, and recent and past depression--were significantly associated with suicidal behavior in the three groups of children.
Pregnancy outcome in patients treated for Hodgkin's disease.
Authors: J Aisner, P H Wiernik, P Pearl
Journal: Journal of Clinical Oncology (1993)

PURPOSE This study attempted to determine the outcome of pregnancies in patients (or their partners) who were successfully treated for Hodgkin's disease and to assess the effect of treatment on the children of the treated parents. MATERIALS AND METHODS A questionnaire was distributed to and personal interviews were conducted with patients who were of reproductive age at the time of treatment with consecutive protocols of radiotherapy, chemotherapy, or both. Those premenopausal patients (or the sexual partners of patients) who attempted to conceive after successful treatment constituted the study population. Fertility assessment was based only on those patients identified as desiring children. RESULTS Among 391 adult patients, 221 patients (104 females and 117 males) of reproductive age were interviewed. Before treatment, 63 of the 221 patients had 135 pregnancies, which resulted in 118 children, 11 spontaneous abortions, five elective abortions, and one stillborn. After treatment, 94 patients (43 females and 51 males) actively attempted conception; 35 females and 25 partners of male patients had 84 pregnancies, which resulted in 68 living children. Among the 84 pregnancies, there were one premature birth at 29 weeks, three spontaneous abortions, 11 elective abortions, and two stillborn: one at 32 weeks and one set of twins. The children have been observed for a median of 11 years (minimum follow up &gt; 4.5 years). Of those patients who desired children, 35 of 43 females became pregnant, whereas only 25 of the 51 partners of male patients became pregnant. At least five male patients with low sperm counts apparently fathered children. CONCLUSIONS This study demonstrates that both men and women have the potential for fertility after treatment regardless of treatment modality. The partners of male patients who were treated with combined modality treatment had a lower frequency of pregnancy than did the female patients who attempted conception and their frequency of pregnancy was also lower than the general population. There was no apparent increase in complications of pregnancy, spontaneous abortions, or congenital abnormalities after treatment compared with pregnancies in this patient group before treatment or with pregnancies in the general population.
Prediction of sensitivity to 5-fluorouracil by quantitative measurement of 5-fluorouracil metabolism-relating gene expression in gastric and colorectal cancer
Authors: M. Terashima, M. Kato, Y. Satoh, Y. Odashima, N. Soeta, S. Ohtani, S. Kashimura, Y. Hoshino, M. Kogure, M. Gotoh
Journal: Journal of Clinical Oncology (2005)

4143 Background: Five-fluorouracil (5-FU) is still one of the key-drug for chemotherapy in gastric and colorectal cancer. Therefore, prediction of 5-FU sensitivity is of great importance for chemotherapy in these types of cancer. In the present study, we investigated the role of gene expression levels of 5-FU metabolism-relating enzymes on tumor sensitivity to 5-FU in gastric and colorectal cancer. The investigated genes were as follows; tymidylate synthase (TS), orotate phosphoribosyl transferase (OPRT), thymidine phosphorylase (TP), ribonuclease reductase (RNR) and dihidropyrimidine dehydrogensa (DPD). Methods: Tumors were obtained from 45 patients with gastric cancer and 30 patients with colorectal cancer. Gene expression levels were determined by quantitative real-time reverse transcription polymerase chain reaction. TS and DPD protein levels were also determined by ELISA. Tumor sensitivity to 5-FU was evaluated by in vitro ATP assay. Results: Although DPD mRNA level did not correlate with DPD protein level, TS mRNA level significantly correlated with TS protein level (r=0.535, p=0.0002). There were significant correlations between TP and DPD, OPRT and RNR gene expression levels and between OPRT and RNR gene expression levels. In concerning with the 5-FU sensitivity, DPD expression levels in gastric(r=-0.635, p=0.0246) and colorectal cancer (r=- 0.469, p=0.0419) and TP expression level in gastric cancer (r=-0.525, p=0.080) showed weak inverse correlation with 5-FU sensitivity. However, OPRT/DPD mRNA ratio significantly correlated with 5-FU sensitivity in both gastric (r=0.780, p=0.0104) and colorectal cancer (r=0.674, p=0.0097). High OPRT/DPD ratio resulted in high sensitivity to 5-FU. Conclusions: From these results, it is suggested that tumors with high anabolic enzyme mRNA and low catabolic enzyme mRNA show remarkable sensitivity to 5-FU in gasric and colorectal cancer. Quantitative measurement of 5-FU metabolism-relating gene expression levels may be a good indicator for predicting sensitivity to 5-FU in patients with gastric and colorectal cancer. No significant financial relationships to disclose.
A phase I/II trial of weekly docetaxel and gefitinib in elderly patients (≥ 70) with stage IIIB/IV non-small cell lung cancer (NSCLC)
Authors: T. E. Stinchcombe, M. A. Socinski, J. Choksi, K. Bakri, M. Taylor, M. T. Tynan, A. Mears, C. Smith
Journal: Journal of Clinical Oncology (2005)

7259 Background: The optimal treatment for elderly patients with NSCLC continues to be an area of active investigation. Recently docetaxel on a weekly treatment schedule and gefitinib have both demonstrated activity and an acceptable toxicity profile. Methods: Elderly pts (age ≥ 70), with stage IIIB/IV NSCLC, and performance status (PS) 0–2 were treated with gefitinib (250 mg daily) and docetaxel days 1, 8, 15 every 28 days initially at 30 mg/m2 (phase I) and subsequently 36 mg/m2 (phase II). Treatment was continued until disease progression or unacceptable toxicity. The primary objective was response rate, and secondary objectives were time to progression, quality of life, and toxicity profile Results: 20 patients have been treated and response data is available on 17 patients. Patient demographics (#): Median age 76.2 (range 70–83), PS: 0 (3) 1 (13) 2 (4), Stage: IIIB (4) /IV (16), Sex: female (9), male (11). 5 patients had a response (29%), 3 had stable disease (17%), 7 had progressive disease (39%), 2 had non-evaluable disease (12%). Toxicity data (19) reveals grade 3 or 4 toxicities at ≥ 10%: anemia 10%, cardiovascular 15% (DVT/PE 10%, supraventricular arrhythmia 5%), anorexia 10%, nausea 16%, vomiting 10%, dehydration 20%, diarrhea 15%, and infection 16% (pneumonia 5%, and UTI 10%). Pulmonary toxicity has been cough 10%, dyspnea 21%, and pneumonitis 16% Conclusions: The combination of weekly docetaxel and gefitinib appears to have activity based on this preliminary analysis; however, definitive conclusions about the toxicity and survival profile of this combination will require further follow-up Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca, Aventis AstraZenca, Aventis
Medical Certification of Cause of Death
Journal: BMJ (1952)

Medical certification of cause of death [MCCD] scheme is an important tool to obtain scientific and reliable information in terms of causes of mortality. It is basically a part of International Statistical Classification of Diseases and health related problems formulated by WHO. Because of this importance, a provision has been made in Registration of Births and Deaths Act, 1969 for certification by a medical practitioner who has attended the deceased during his last illness. Till now this scheme is not uniformly covered and implemented in India. An overview of this scheme is presented herewith.
A phase I clinical and pharmacokinetic (PK) study of oral CI-1033 + docetaxel (DOC) in the treatment of patients with advanced solid tumors
Authors: J. P. Eder, M. Hidalgo, D. Mendelson, P. D. Ryan, B. Arun, J. Lovalvo, I. Eiseman, S. Olson, P. Lenehan, L. L. Garland
Journal: Journal of Clinical Oncology (2005)

3111 Background: CI-1033 is an orally available 4-anilinoquinazoline that is an irreversible tyrosine kinase inhibitor of erbB-1, -2 and -4. We conducted a dose escalation study of CI-1033 with DOC to assess the safety profile and PK of the combination and to establish the maximum tolerated dose (MTD). Methods: DOC was given intravenously on Day 1 and CI-1033 was given as a single oral dose daily from Days 2–14 of a 21-day cycle. Results: 26 patients (pts) were enrolled onto 4 dosing cohorts (see table). Dose-limiting toxicities (DLTs) were noted in cohorts 2–4 (see table). Although febrile neutropenia (FN) was expected with DOC, a 38% incidence of cycle 1 FN in cohort 2 was considered excessive and prompted dose de-escalations of both study drugs in cohort 3. The most common all-causality adverse events were asthenia (73%), leukopenia (73%), rash (58%), diarrhea (54%), and stomatitis (54%). PK data for 7 pts suggested negligible CI-1033 accumulation following 15 days of dosing. The 8-hour CI-1033 PK profile was consistent with data derived from prior Phase 1 experience. Day 1 DOC PK was consistent with DOC PK literature. Objective antitumor activity included one complete response in a pt with adenocarcinoma of the cervix (cohort 3), one partial response in a pt with NSCLC (cohort 4), and stable disease (>18 wks) in one pt with ureteral cancer (cohort 4). Conclusions: The MTD for CI-1033 + DOC is 45 mg/day + 60 mg/m2, respectively. FN, a frequent cycle 1 event, prompted dose de-escalation. There were no apparent PK interactions between CI-1033 and DOC. Antitumor activity was noted in 3 patients, including at the MTD. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer Pfizer Pfizer Pfizer
Detection of minimal residual disease (MRD) in peripheral blood of primary breast cancer patients: Translational research in the SUCCESS study
Authors: J. K. Jueckstock, B. Rack, E. Thurner-Hermanns, H. Forstbauer, K. Pantel, H. Ulmer, M. Beckmann, W. Lichtenegger, W. J. Janni, K. Friese
Journal: Journal of Clinical Oncology (2007)

565 Background: Patients with detection of MRD in bone marrow are known to have an increased risk for recurrence and a poorer clinical outcome. However, peripheral blood would be the preferable compartment to monitor treatment efficacy due to increased feasibility. The translational research program of the German SUCCESS-trial was established to evaluate MRD in peripheral blood at 4 different time points during adjuvant systemic treatment of breast cancer patients. Here first results of the detection of MRD at primary diagnosis and after adjuvant chemotherapy will be presented. Patients and Methods: Cells were separated by Ficoll-Hypaque density- gradient centrifugation followed by labelling of epithelial cells with the anti-cytokeratine-antibody A45-B/B3 (directed against cytokeratines 8, 18 and 19) and immunohistochemically staining with neu-fuchsin. All preparations were screened by two independent persons. Results: 328 breast cancer patients were analyzed at primary diagnosis. Among those, 133 patients returned for a 2 nd blood sampling after completion of adjuvant chemotherapy. Most of the tumors were small (43% pT1, 51% pT2, 4% pT3, 1% pT4) but of intermdediate or unfavourable grade, (G1 7%, G2 48%, G3 45%). 66% of the patients were node-positive (34% pN0, 38% pN1, 20% pN2, 8% pN3) and a positive hormone receptor status was seen in 71%. In 22% the Her2-status was positive. MRD in peripheral blood was found in 31% of all patients before and in 9% after chemotherapy. The mean number of detected cells was 2 (range 1- 9). In 87,2 % of the patients who showed MRD at the first measurement no MRD was detected after chemotherapy. 16% of patients without detection of MRD at primary diagnosis showed MRD after chemotherapy. Neither tumor size (p= 0.624), lymph node metastases (p= 0.450), histopathological grading (p= 0.168), hormone receptor status (p= 0.270) or Her2/neu status of the primary tumor (p= 0.893) correlated with the presence of MRD. Conclusions: The detection of MRD in peripheral blood can be widely used and is suitable for repeated measurements. Further follow-up will show, if this method can be used for risk stratification and monitoring of treatment efficacy in adjuvant breast cancer. No significant financial relationships to disclose.
Her2 expression in gastroesophageal cancer (GEC) FFPE tissue using mass spectrometry (MS) and correlation with <i>HER2</i> gene amplification.
Authors: Daniel Virgil Thomas Catenacci, Lei Zhao, Emma Whitcomb, Les Henderson, Emily O'Day, Peng Xu, Shu-Yuan Xiao, Sang Mee Lee, Wei-Li Liao, Sheeno P Thyparambil, Jamar Uzzell, Marlene Darfler, David Krizman, Jon Burrows, Todd A. Hembrough
Journal: Journal of Clinical Oncology (2015)

82 Background: HER2+ GEC derived benefit from trastuzumab. Her2 IHC is semi-quantitative, subjective, and sensitive to antigen instability; HER2 FISH is laborious, expensive, and subjective. False positivity/negativity have been described. Also, these are low throughput assays; there is known molecular heterogeneity, with several putative biomarkers, and only scarce tissue to assess for each. We sought to evaluate the association of Her2 MS expression with HER2 FISH, along with other markers within the ‘GEC-plex’. Methods: We utilized a previously described unique Her2 peptide and quantification method (Hembrough et al J Clin Oncol 32,2014(suppl 3;abstr17)). The assay was run on 27 cell lines, in parallel with HER2:CEP17 FISH. Her2 expression thresholds were established for HER2 amplification using ROC curves. We adjusted for Her3, Egfr, and Met MS expression levels and sample HER2:CEP17 ratio heterogeneity in a multiple linear regression model. The model/cut-offs were then validated prospectively on GEC tissues (n=142). Results: Her2 MS on cell lines revealed concordance with FISH (HER2:CEP17) ratio (R 2 =0.75), which improved by adjusting for Her3 MS, Egfr MS, Met MS and HER2:CEP17 heterogeneity (R 2 &gt;0.98), with significant interactions. IHC correlation with HER2:CEP17 ratio was poor (R 2 =0.12). A wide range of expression was noted within IHC3+ patients (&lt;150-24671amol/ug). Her2 MS expression (&gt;150 amol/ug) was seen in 72.9% (102/142) of tissues (range &lt;150-24671amol/ug); 9.9% (14/142) had Her2 &gt; 750 amol/ug - all were HER2 FISH amplified. 6/142 (4%) cases &lt;500 amol/ug were clinically ‘HER2amplified’. IHC/FISH results for cases with 550-750 amol/ug demonstrated an ‘equivocal’ zone, not unlike ‘IHC 2+’, but less frequent (8/142, 5.6% vs 46/142 32.4%). Conclusions: The MS HER2 assay can be multiplexed with other GEC biomarkers. A robust model was developed that showed strong correlation of Her2 MS with HER2:CEP17 ratio, particularly when adjusting for covariates Egfr MS, Met MS, Her3 MS, and HER2 FISH heterogeneity. Future analysis will assess the established model as a tool for better prediction of therapeutic benefit from anti-Her2 therapy compared to current methods.
Alkaline Phosphatase Improves Kidney Function in Icu Patients With Sepsis-induced Acute Kidney Injury
Authors: P. Pickkers, Pierre-François Laterre, J. Schouten, J. L. Vincent, J. Groeneveld, P. Jorens, H. Spapen, S. Heemskerk, H. van der Hoeven
Journal: Intensive Care Medicine (2010)