tbuckley/cabot-search huggingface dataset:
MLH1 and BRAF status analysis in metastatic germ cell tumors.
Authors: J. M. Piulats, A. Vidal, A. Villanueva, C. Muñoz, A. Pisa, M. Nadal, J. R. Germa-Lluch, E. Condom, X. Garcia del Muro
Journal: Journal of Clinical Oncology (2010)

e15092 Background: Germ cell tumors (GCTs) are the most common malignancy in young men. Recently have been proposed Mismatch repair (MMR) deficiency, microsatellite instability (MSI) and BRAF mutations to be related with cisplatin (CDDP) resistance in nonseminomatous (NSE) GCTs. On the other hand, we wanted to use our orthotopic nude mice GCTs implantation model for microsatellite instability (MSI) study. Methods: A retrospective cohort of 75 male patients with metastatic germ cell tumors treated at the Catalan Cancer Institute from August 1989 to November 2004 was chosen to generate a tissue microarray. We identified he presence of the MMR factor MLH1 by immunohistochemistry (IHC) using the G168-728 antibody. We performed a double check for BRAF mutations in paraffin embedded tissue using restriction fragment length polymorphism (RFLP) with the Spel restriction enzyme; and single strand conformation polymorphism (SSCP) analyses. SK-Mel28 and RKO cell lines were used as positive controls for BRAF mutations in homozygosis and heterozygosis respectively. We have generated resitance to CDDP in vivo in five tumors by exposition to repetitive cycles (1 yolk-sac; 1 choriocarcinoma; 2 embrional carcinoma; 1 mix tumor). Initial tumors and their respective CDDP resistant induced tumors were checked for MSI using the Promega commercial kit that include BAT26, BAT25, NR21, NR24 and MONO27 markers. Results: Median age was 28 years (16-56). 16% were seminoma and 84% NSE. One third of patients were refractory to first line CDDP based chemotherapy. All samples stained positive for MLH1 and we did not identify any BRAF mutation in sensitive patients neither in refractory ones. None of the xenografted tumor did show MSI in the locus analyzed in the original and the CDDP refractory in vivo induced tumors. Conclusions: In our series MLH1 inactivation and BRAF mutations do not seems to be involved in CDDP resistance. We are analyzing MSH2 and MSH6 expression by IHC as well as checking refractory tumors for BRAF mutations with a third technique using a multiplex SNaPshot. No significant financial relationships to disclose.
Abstract P205: Fair Agreement Between Stroke Patients and Family Members for Ascertaining Pre-Stroke Risk of Sleep Apnea
Authors: Sarah Reeves, Devin Brown, Ronald Chervin, Lewis Morgenstern, Melinda Smith, Lynda Lisabeth
Journal: Circulation (2012)

Background Obstructive sleep apnea is a risk factor for ischemic stroke and may play a role in post-stroke outcomes. Ascertaining self-reported information about pre-stroke sleep apnea risk in the acute stroke period is challenging as many stroke patients have deficits that hinder communication. We examined agreement between stroke patients and family members (proxy) with respect to pre-stroke risk of sleep apnea and hypothesized that agreement would be good. Methods Patient-proxy pairs (n=38) were interviewed as part of the Brain Attack Surveillance in Corpus Christi Project from May 2010 - April 2011. The Berlin Questionnaire was used to measure high risk of sleep apnea defined as at least two of the following: 1) snoring behaviors and witnessed apneas 2) daytime sleepiness and 3) hypertension or obesity. Patient-proxy agreement was assessed using a kappa coefficient. Results Average patient age was 70 (SD=12 years), 68% (n=26) were Mexican American and 32% (n=12) non-Hispanic white. An equal number of male and female patients participated (n=19), and average NIH Stroke Scale value at admission was 5.5 (SD = 6.4). Proxies were spouses (n=24) or children (n=14). Proxies had known patients for an average of 40 years (SD=15) and spoke with the patient daily (n=37) or weekly (n=1). Forty percent of patients (n=15) self-identified as high risk for sleep apnea and 52% of proxies (n=20) identified patients as high risk. Patient-proxy agreement for high risk of sleep apnea was fair (kappa=0.43; table 1 ) and was the same for both spouses and children. Conclusions Proxies can be used to assess pre-stroke risk of sleep apnea when a stroke patient is unable to participate as agreement for high risk of sleep apnea was fair. Proxies reported a high risk for sleep apnea with greater frequency than patients, suggesting there may be differences in observation of specific high-risk characteristics between proxies and patients. Table 1. Patient-Proxy Agreement for Risk of Sleep Apnea (n=38) Patient Risk Assessment Proxy Risk Assessment Total Low High Low 15 8 23 High 3 12 15 Total 18 20 38
Phase II trial of extended-dosing temozolomide in patients with melanoma
Authors: P. Rietschel, S. Ejadi, J. Wolchok, S. Krown, S. Gerst, A. A. Jungbluth, K. Busam, K. Smith, K. Panageas, P. Chapman
Journal: Journal of Clinical Oncology (2006)

8042 Background: We previously reported a 30% response rate in metastatic melanoma (mel) patients (pts) treated with temozolomide (TMZ) using an extended dosing schedule of 6 weeks on/ 2 weeks off with either thalidomide or interferon. We hypothesized that these responses were largely due to TMZ alone and conducted a phase II trial using extended dosing TMZ alone. We also tested the hypothesis that a) mel expression of methylguanine methyltransferase (MGMT) would correlate with drug resistance, and b) TMZ would cause decreased CD4 + T cell function during the first cycle of therapy. Methods: A phase II trial stratified metastatic mel patients into two cohorts based on whether or not they had stage IV M1c. 25 patients/cohort are planned. No brain metastases or prior chemotherapy were allowed. Each cycle consisted of TMZ 75mg/m 2 /day for 6 weeks followed by 2 weeks with no treatment. Primary endpoint was the proportion of objective responses by RECIST criteria. The trial was powered to exclude the null hypothesis that the response rate in each cohort was ≤10%. MGMT promoter methylation status was assessed by methylation-specific PCR. MGMT tumor expression was measured by immunohistochemistry (IHC). CD4 + T cell function was assessed by measuring interferon-γ responses to CMV by intracellular cytokine FACS analysis (FastImmune, BD Biosciences) at pretreatment, week 4 and week 8 of cycle 1. Results: To date 19 evaluable pts, 8 in the M1c cohort, have progressed with no objective responses; 6 other patients are currently on study. 4/19 pts who have gone off study because of progression were stable for 6 months and received ≥3 cycles. To date, 14/15 tumors analyzed for MGMT promoter methylation were unmethylated (≤15%). Promoter methylation of 21% was seen in one tumor. Conclusions: The MGMT promoter of metastatic mel tumors are hypomethylated predicting expression of the enzyme. This is being assessed directly by IHC and will be correlated with promoter methylation and clinical response. The effect of TMZ on anti-CMV CD4 + T cell function is being assessed. Accrual is ongoing and will be completed in Spring 2006. The study was supported by Schering-Plough. No significant financial relationships to disclose.
원저 : 간동맥 조영술을 시행한 장경 5 cm 이하의 간암 환자에서 치료방법 , 간기능에 따른 치료성적
Authors: 송건훈, 한광협, 문영명, 전재윤, 최원, 이관식, 박인서, 김병로, 이종태 ( Kun Hoon Song), Kwang Hyub Han, Young Myung Moon, Chae Yoon Chon, Won Choi, Kwan Sik Lee, In Suh Park, Byong Ro Kim, Jong Tae Lee
Journal: Clinical and Molecular Hepatology (1996)

Background/Aims . To compare treatment outcome of hepatocellular carcinoma(HCC) under the size of 5 cm in relation to underlying liver function and treatment modalities, analysis of data from 145 patients was performed. Methods '. In this study, the records of 145 patients with small HCC ( 40 ng/mL) serum alpha-fetoprotein(AFP) level. Liver cirrhosis was associated in 109(75.2%) patients. Sixty five(44.8%) patients underwent surge, 63(43.5%) underwent transarterial therapy(TAT), 8(5.5%) underwent other modalities of therapy and the remaining 9(6.2% ) patients did not receive any specific treatment for HCC. In relation to the underlying liver function, 119(82.1% ) patients belonged to the non-cirrhotic or Child-Pugh class A, 20(13.8%) to class B and 6(4.1%) to class C. The median follow-up duration was 21 months. When analyzed with respect to treatment modalities alone, median survival was 43 months for all patients, 60 months for surgery, 29 months for TAT, 20 months for other treatment and 18 months for patients who received no specific treatment. Without considering liver function, cumulative 3  year survival rate was 68.6% for surgery, 43.9% for TAT, 29.2% for other treatment  and 0% for no treatment. The survival rate for the patients who underwent surgery was significantly higher than for any other treatment modalities without considering the underlying liver function or in the non-cirrhotic/Child-Pugh class A(p 0.05). But in patients classified as the non-cirrhotic/Child-Pugh class A, better survival was observed in the surgep group than the TAT group(p<0.05). The only factor influencing survival was the pre-treatment serum AFP level(p<0.05). The overall recurrence rate was 30.3%. For the entire patients, the factor significantly influencing the recurrence rate was the presence of underlying cirrhosis. When considering only the patients in the surgery group, the different types of surgical procedures significantly influenced the recurrence rate. Conclusion .' Surgery is the treatment of choice for patients with HCC equal to or smaller than 5 cm. But for those patients whose tumor size is less than 3 cm, TAT may be a reasonable alternative to surgep when the liver function is not adequate for hepatic resection. Because overall recurrence rate exceeded 30% and median time of recurrence was only 9.5 months after definitive treatment, careful follow-up is required for all patients who undergo treatment for small HCC.
Disappearance of Nitrite From the Rat Stomach: Contribution of Emptying and Other Factors&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: S S Mirvish, K Patil, P Ghadirian, V R Kommineni
Journal: JNCI Journal of the National Cancer Institute (1975)

To help understand how intragastric nitrosation forms N-nitroso compounds, nitriet disappearance from the rat stomach was measured after food containing nitrite was given. In preliminary experiments, nitrite disappearance from buffered aqueous solutions became more rapid as the pH was lowered from 5 to 1 and, at a given pH, was more rapid in a slurry of commercial rat food. The disappearance of nitrite from buffer was little affected by the addition of pepsin, mucin, albumin, or rat gastric contents. When starved rats were given 5 g food with 1.82 mg nANO3/g, nitrate was not reduced to nitrite in the stomach. Five g food containing 154 mug NaNO2/g was administered similarly, and the total stomach (T) and glandular and nonglandular parts (G and NG) were analyzed after 1.5 hours. Weight and nitrite concentration of the stomach contents dropped linearly and the amount of nitrite dropped exponentially (with a half-life of 1.4 hr). Mean nitrite concentration in G was less than half that in NG. From similar experiments with phenol red, emptying accounted for 60% of nitrite loss from T. In G, nitrite concentration was reduced about 3 times due to dilution and 3 times due to other causes. Conditions in G, e.g., nitrite concentration, pH, and empyting time, were discussed in relation to carcinogenesis experiments with nitrite plus amines and amides.
Effects of Cimetidine on Tumor Growth and Immune Function in Nude Mice Bearing Human Ovarian Carcinoma&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Y Kikuchi, K Oomori, I Kizawa, K Kato
Journal: JNCI Journal of the National Cancer Institute (1985)

The effects of cimetidine on the growth of a human ovarian cancer cell line inoculated into BALB/c nude mice were examined. The cell line, designated "KK," was derived from a cystadenocarcinoma of the ovary. The passage number was about 40, and its tumorigenicity in nude mice was 100% even when 10(5) cells were inoculated. About 2 weeks after inoculation, the KK cells formed palpable tumors, and the tumor volume reached 2.29 cm3 on day 36. Conversely, the nude mice given cimetidine (100 mg/kg/day) orally with drinking water had about one-third the tumor volume (0.81 cm3) of that in untreated nude mice on day 36. The natural killer activity against the YAC-1 (a T-cell lymphoma) cell line in spleen cells of the nude mice challenged with human xenogeneic tumor (KK cell line) was not affected by treatment with cimetidine while inhibiting the tumor growth. The capacity to lyse the KK cells did not exist in the spleen cells of nude mice challenged with the KK cell xenograft and not treated with cimetidine. The cimetidine-treated spleen cells acquired the capacity to lyse the KK cells on day 14. Thereafter, the capacity was maintained at the same level as long as cimetidine was administered, whereas that in untreated nude mice remained undetectable.
Simultaneous measurements of glomerular filtration rate by two radioisotopic methods in patients without renal impairment.
Authors: D K Klassen, M R Weir, E U Buddemeyer
Journal: Journal of the American Society of Nephrology (1992)

Isotopic clearance techniques have been widely used to measure GFR but may give variable results depending on the level of renal function and the technique used. GFR, measured by the technique of plasma disappearance of 99mTc-labeled diethylenetriaminopentacetic acid ([99mTc]DTPA) was compared with simultaneously obtained urinary clearance of [99mTc]DTPA. GFR was also measured by concurrent 24-h clearance of creatinine. Forty-six measurements of GFR were obtained in 12 patients who had no evidence of renal disease. Plasma disappearance was measured from three timed plasma samples collected 60 to 180 min after the bolus injection of 200 microCi of [99mTc]DTPA and was calculated as the product of the volume of distribution (milliliters) at time zero and the clearance rate (per minute) as determined by the regression of the monoexponential plot. Urinary clearance was measured as the average of 3 1-h urinary clearances collected after a water diuresis was established. GFR measured by plasma disappearance was significantly greater (P less than 0.001) than GFR measured simultaneously by urinary clearance. There was a linear correlation between GFR measured by urinary clearance and that measured by plasma clearance (r = 0.994). Plasma clearance exceeded urinary clearance by a constant factor of 1.3 over the range studied (urinary clearance range, 49 to 94 mL/min/1.73 m2). It was concluded that at relatively a normal GFR, the plasma clearance of [99mTc]DTPA consistently overestimates the urinary clearance of [99mTc]DTPA.
The expression of CD26 and CD40 ligand is mutually exclusive in human T- cell non-Hodgkin's lymphomas/leukemias
Authors: A Carbone, A Gloghini, V Zagonel, D Aldinucci, V Gattei, M Degan, S Improta, R Sorio, S Monfardini, A Pinto
Journal: Blood (1995)
Various phenotypes of COPD are closely related to regulatory T cells
Authors: Elena Kremer, Natalya Kirillova, Ivan Deev, Georgij Chernogoruk, Ludmila Ogorodova
Journal: European Respiratory Journal (2011)

Background: Regulatory T-cells (T-reg) play an important role in physiology and pathology of immune system and take essential place in pathogenesis of various autoimmune, tumoral and allergies diseases. However, T-reg subpopulations in separate phenotypes of COPD remain insufficiently studied.

Aim and objectives: To investigate different subpopulations of T-reg in patients with various phenotypes of COPD.

Methods: Levels of natural CD4+CD25high and inducible CD4+FoxP3+ T-reg were analyzed in 60 subjects with COPD (including 13 subjects diagnosed with emphysematous phenotype, 28 patients with bronhitich phenotype,19 subjects with mixed phenotype of COPD) and 17 healthy subjects (HS) using the flow cytometry analysis.

Results: CD4+CD25high in COPD were significantly increased compared to HS (2,82±0,24%, p = 0,005; 1,56±0,24%, p = 0,005, respectively). Increased level of CD4+CD25high was shown for persons with emphysematous phenotype (3,45±0,40%, p = 0,021) compared to persons diagnosed with bronhitich (2,83±0,22%, p = 0,021) and mixed (2,38±0,22%, p = 0,014) phenotypes of COPD. As for CD4+FoxP3+ T-reg no difference between different phenotypes of COPD and HS was observed.

Conclusions: Different subpopulations of T-reg may determine various phenotypes of COPD and this study indicates that increased level of CD4+CD25high is associated with emphysematous phenotype of COPD to support this hypothesis.
Radioresistance of Phytohemagglutinin-Treated Normal and Leukemic Lymphocytes&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: R SCHREK, S STEFANI
Journal: JNCI Journal of the National Cancer Institute (1964)

The effects of phytohemagglutinin (PHA) and X rays on suspensions of lymphocytes from normal human blood incubated in small test tubes for 6 days at 37° C were studied. Viable cell counts of untreated control suspensions showed that 63 percent of the lymphocytes survived incubation. Incubation of purified suspensions of lymphocytes with PHA resulted in enlargement of many lymphocytes, formation of some lymphoblastoid cells, and a few mitotic divisions. Irradiation of blood cell suspensions killed many lymphocytes, so that only 10 percent survived 6 days after a dose of 75 r and 5 percent after 150 r. PHA-treated suspensions were irradiated with 75 to 2400 r. Many lymphocytes and transformed lymphocytes survived irradiation even with a dose of 1200 and 2400 r. It was concluded that addition of PHA protected lymphocytes against the cytotoxic effects of irradiation. Radio-protection of lymphocytes was observed whether the PHA was added at any time from 4 days before to 2 days after irradiation with 300 r. Blood lymphocytes from 3 of 6 patients with chronic lymphocytic leukemia showed little or no radioprotection with PHA. The morphologic reaction of lymphocytes from leukemic patients was usually less than that observed with normal lymphocytes. One of the 6 patients with chronic lymphocytic leukemia had blood lymphocytes resistant to X irradiation with 2400 r even without PHA.
포스터전시 : 문맥 침범을 동반한 진행성 간세포암에서 크기와 형태에 따른 3차원 입체조형 방사선치료효과
Authors: 조성범, 이석, 윤경원, 박선영, 이완식, 박차완, 김현수, 최성규, 유종선
Journal: Clinical and Molecular Hepatology (2008)
Compliance with practice guidelines for node-negative breast cancer.
Authors: A Olivotto, A J Coldman, T G Hislop, C H Trevisan, J Kula, V Goel, C Sawka
Journal: Journal of Clinical Oncology (1997)

PURPOSE Practice guidelines for cancer management have been in use in the province of British Columbia (BC), Canada, since the mid 1970s. To evaluate practice guideline compliance, treatment received was compared with treatment recommended in a population-based cohort of women with breast cancer. METHODS All incident cases (n = 939) of invasive, pathologically node-negative breast cancer diagnosed in 1991 were identified from the BC Cancer Registry. Treatment details were abstracted from cancer clinic records for cases referred to the BC Cancer Agency (BCCA) (n = 661) and original source documents for nonreferred cases. Management decisions were considered compliant if the patient received the recommended treatment or was entered onto a randomized trial of the modality being assessed. RESULTS Overall compliance with adjuvant therapy guidelines was 97% for radiotherapy, 96% for chemotherapy, and 89% for tamoxifen. An oncology specialist was consulted by 94% of patients with an indication for adjuvant treatment and by 58% of those without an indication (odds ratio [OR] = 10.7; 95% confidence interval, 7.0 to 16.4). Compliance with a guideline to deliver radiotherapy was 95%; with chemotherapy, 77%; and with tamoxifen, 68%. Compliance with a guideline that stated no adjuvant treatment was indicated was 99% for radiotherapy, 98% for chemotherapy, and 92% for tamoxifen. Noncompliance among patients with an indication for treatment was related to nonreferral to an oncology specialist and less complete implementation of guideline changes in the community as compared with cancer center practices. CONCLUSION Compliance was high, but scheduled updating and more effective community implementation could further improve consistency of care.
Caveolin-1 regulation of BCL-2 in paclitaxel-mediated apoptosis in breast cancer
Authors: Zachary Dobbin, Ayesha Shajahan, Robert Clarke
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

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Breast cancer is one of the most common cancers afflicting woman in the U.S. In 2007, approximately 240,000 new cases of breast cancers will be diagnosed. Taxanes are chemotherapeutic drugs, e.g. paclitaxel (Taxol), that are potent anti-tumor agents that repress the dynamic instability of microtubles and arrest cell cycle. Although, paclitaxel is a potent chemotherapy drug, it is non-specific. Moreover, cancer cells can develop resistance to these drugs over time and this remains a major problem in therapy. Caveolin1 (CAV1) is an integral membrane protein that forms the structural foundation of caveolae. CAV1 is not just localized to the plasma membrane but is also found in the cytoplasm and other organelles including the mitochondrial membrane. The role of CAV1 varies in different cancers, however in breast cancer, CAV1 has an anti-tumorigenic effect. Our laboratory has shown that treatment of breast cancer cell lines with paclitaxel results in up-regulation of CAV1 and an increase in mitochondrial membrane permeability. BCL-2 plays an anti-apoptotic role in breast cancer. A primary role of BCL-2 is to stabilize the mitochondrial membrane. BCL-2 is also an integral membrane protein that will promote tumorigenesis by preventing cell death. BCL-2 is regulated via phosphorylation at a Ser70 residue causing it to lose its anti-apoptotic activity. We have previously shown that Ser70 phosphorylation, and hence inactivation of BCL-2, is more readily induced by paclitaxel in MCF7 cells that overexpress wild-type CAV1 (wt-CAV1) versus in MCF7 cells expressing the empty vector (EV). Thus, we hypothesize that increased mitochondrial permeability, and therefore, apoptosis is mediated by CAV1 regulation of BCL-2 following paclitaxel treatment in MCF7 breast cancer cells. Western blot analysis has shown that expression of wtCAV1 in MCF7 cells decreases the expression of BCL-2 compared to MCF7-EV. We show that in MCF7-wtCAV1 cells, relative mRNA levels of BCL-2 do not increase as in MCF7-EV cells following paclitaxel treatment. Decreased levels of BCL-2 in MCF7-wtCAV1 cells correlate with increased sensitivity to paclitaxel. We show that both CAV1 and BCL-2 are localized in the mitochondria in the MCF-wtCAV1 cells. By immunoprecipitation from whole cell lysates, we show that BCL-2 forms a complex with CAV1 when treated with 10 nM paclitaxel. Thus, our study shows a relationship between CAV1 and BCL-2 in paclitaxel induced mitochondrial permeability. Future studies will focus on measuring co-localization of CAV1 and BCL-2 in the mitochondria and determine what role CAV1 plays in the regulation of transcription of BCL-2. Our results will help accentuate our knowledge of chemotherapeutic drug targets that can increase the efficacy-to-toxicity ratio in breast cancer patients.