tbuckley/cabot-search huggingface dataset:
The effects of estrogen and progesterone on KLK 5 secretion and expression in SKOV-3 cells
Authors: Sharmeka Elliott, Gloria Regisford, Douglas Cordella Brown, Robert McClintock, Clarissa Durand-Rougely
Journal: Cancer Research (2008)

3153  Ovarian cancer, the deadliest of all gynecological carcinomas, is linked to kallikreins (KLK), a novel family of 15 serine proteases. An increased level of KLK 5 has been associated with bad prognosis of ovarian cancer. Reports indicate that the ovarian steroid hormones, estrogen (E2) may promote the onset of ovarian cancer, while P4 may play a protective role against the progression of this fatal cancer. Therefore, our objective was to determine the effect of E2 and P4 treatment on the secretion and expression of KLK 5 in an ovarian cancer cell line, SKOV-3. We hypothesized that E2 will increase, while P4 will decrease KLK 5 secretion and expression. We also postulated that there will be no synergistic effect of the combined E2 and P4 treatment on KLK 5 secretion and expression, and further, that cells primed with E2 and then treated with P4 will show a marked decrease in KLK 5. SKOV-3 cells were treated with (1) 10-8M E2; (2) 10-6M P4; (3) 10-8M E2 + 10-6M P4 for a period of four days and (4) 10-8M E2 for two days followedby 10-6M P4 for a period of two days. Culture supernatants were collected daily and the concentration of KLK 5 was determined by an enzyme linked immunosorbant assay (ELISA). After treatment, cells were then harvested, total protein extracted, and the expression of KLK 5 in E2-and P4-treated SKOV-3 cells was determined by Western blot analysis. On days 3 and 4 of treatment, supernatants from cells treated with E2 and P4 or E2/P4, tended to have lower KLK 5 concentrations than supernatants from cells treated with E2 and P4 alone. The expression of KLK 5 was slightly down regulated in SKOV-3 cells that were treated with E2 compared to control. There was no detection of KLK 5 expression in cells treated with P4; E2 and P4; or E2 followed by P4. Our data suggests that E2 and P4 may act synergistically in reducing KLK 5 secretion, while any exposure to P4 (alone or in combination with E2) may significantly reduce KLK 5 expression in ovarian cancer.
Association of MicroRNA 211 expression with prognosis in colorectal cancer: A case-control study.
Authors: Ahmet Taner Sümbül, Bulent Gogebakan, Serdar Oztuzcu, Erhan Yengil, Ahmet Sezer, Huseyin Abali
Journal: Journal of Clinical Oncology (2014)

e14603 Background: Increasingly more evidence support the role of the micrornas in tumorgenesis. miR-211 is a microrna that acts as a tumor suppressor at a posttranlational level in colorectal cancer and it targets chromodomain helicase DNA binding protein 5 (CHD5). We, for the first time, analyzed 66 colorectal cancer patients that were operated on in our hospital for the miR-211 levels in normal and cancerous area in cancer patients and tissue in the healthy group, and the correlation of the clinicopathological factors to the patient survival rates. Methods: miRNA was isolated from the paraffine tissues of all cases. cDNA was obtained from these miRNAs using the reverse transcriptase method. miR-211 expression levels were determined using the qRT-PCR method. Based on the average miR-211 levels, two groups of low or high expression were formed. Correlation of the patients’ clinicopathological factors and survival was analysed. Results: miR-211 levels in tumorous and normal tissues were determined to be a median in order of 0,000922 (0,0000070-1) and 0,0004 (0,000024-1)(p=0,59). However, in the control group, miR-211 levels were determined to be a median of 0,000256 (0,000031-1)(p < 0,0001). There were 33 (50%) patients that expressed low levels of miR-211, and 33 (50%) patients that expressed high levels of miR-211. The correlation between the miR-211 expression and clinicopathological features was analyzed. No correlation of clinical significance was determined with these parameters. The univariate analysis of the factors that may affect survival indicated invasion depth (p=0,063), lymphovascular invasion (p=0,011), perineural invasion (p=0,009) and miR-211 expression levels (p=0,041) presence to be effective. In the multivariate analysis of these factors with overall survival, only miR-211 expression level (p=0,01) was effective on overall survival. Conclusions: We revealed that colorectal cancer patients express miR-211 at a higher level than the healthy population and this situation is related to poorer prognosis. And we propose to conduct multicenter studies to investigate diagnostic, prognostic and targetable role of miR-211 in colorectal cancer patients.
Systemic chemotherapy compared with radiation therapy as adjuvant therapy after radical surgery in high-risk stage IB-IIB cervical adenocarcinoma.
Authors: Toshiyuki Seki, Hiroshi Tanabe, Chie Nagata, Satoshi Takakura, Seiji Isonishi, Kazuhiko Ochiai, Hiroshi Sasaki, Kazunori Ochiai, Aikou Okamoto
Journal: Journal of Clinical Oncology (2014)

5598 Background: Radiation therapy (RT) and concurrent chemo-radiation therapy (CCRT) are commonly used adjuvant therapies for FIGO stage IB-IIB cervical cancer patients regardless of their histological subtypes. However, given that patients with adeno/adenosquamous carcinoma (AC) reportedly have poorer prognosis compared to patients with squamous cell carcinoma (SCC), a more effective adjuvant therapy targeting AC patients should be investigated. Hence, we conducted this study to evaluate the efficacy of systemic chemotherapy (CT) to AC patients compared with RT/CCRT. Methods: The medical records of the patients with IB-IIB cervical cancer who underwent primary surgery at our 4 institutes from January 2001 to December 2010 were retrospectively reviewed, and the patients with pathologically confirmed bulky tumor (≥4cm), nodal metastasis, and/or parametrium invasion were included. The patients were classified into 3 groups; group 1: patients with SCC who received RT/CCRT, group 2: patients with AC who received RT/CCRT, and group 3: patients with AC who received CT. At first, to determine the efficacy of RT/CCRT to AC patients compared to SCC patients, the progression-free survival (PFS) of group 1 and 2 was compared. Secondly, to investigate the efficacy of CT compared to RT/CCRT for AC patients, the PFS of group 2 and 3 was compared. Results: A total of 135 patients were enrolled (group 1: 90, 2: 23, and 3: 22). The median follow up period was 48 (range: 1-132) months. There was no statistical difference in the proportion of patients with nodal metastasis, parametrial involvement, and bulky tumor between each group. A significant difference in PFS curves was detected between group 1 and 2; AC patients treated with RT/CCRT had poorer prognosis than SCC patients treated with RT/CCRT (RR: 2.504 (95%CI: 1.284-8.871), p=0.014). A significant difference in PFS curves was also detected between group 2 and 3; AC patients had more favorable prognosis when treated with CT compared to RT/CCRT (RR: 0.288 (95%CI: 0.109-0.965), p=0.043). Conclusions: Adjuvant RT/CCRT may be less effective for AC patients, and CT has a potential benefit greater than that of RT/CCRT for AC patients.
Rammya Mathew: Liquid diets offer promise, but we still need upstream solutions
Authors: Rammya Mathew
Journal: BMJ (2019)

When discussing dietary changes with patients I’m often greeted with blank expressions. It may seem simple in theory: eat healthy whole foods with less refined sugar and, dare I say it, fewer carbohydrates. But people find it hard to know where to start when it comes to modifying their diet, and they often have a sense of apathy about being able to lose weight.

The idea of using low calorie, ketosis inducing, liquid diets to lose weight has been trending for some time. Critics argue that such diets are unsustainable1 and unlikely …
A Phase 1 Trial of Ibrutinib (IBR) and Azacitidine (AZA) for the Treatment of Higher-Risk Myelodysplastic Syndromes (HR-MDS): Updated Results of University of California Hematologic Malignancies Consortium (UCHMC) Study 1503
Authors: Brian A. Jonas, Peter T. Curtin, Gary J. Schiller, Deepa Jeyakumar, Matthew J. Wieduwilt, Mehrdad Abedi, Rafael Bejar, Helen Chow, Leslie G. Oesterich, Aaron C. Logan
Journal: Blood (2018)
Abstract P197: Observational Evidence of Intentionality of Weight Loss on All-cause Mortality and Major Cardiovascular Events. Systematic Review and Meta-analysis
Authors: Cristina P Baena, Fernanda Stefani, Priscilla Pietraroia, José Faria-Neto
Journal: Circulation (2017)

Background: The obesity paradox has been described in several cohort studies. However, evidence of intentionality of weight loss on all-cause mortality and major cardiovascular events (MACE) in prospective cohorts is not clear. Aim: To summarize and evaluate the observational evidence of the effects of intentionality of weight loss on MACE and all-cause mortality. Methods: Through a systematic review, multiple electronic databases (MEDLINE/PubMed, Web of Science, SciELO and LILACS) were searched and manual search for studies published up to September 2016 was performed. Cohort studies that reported intentionality (intentional and unintentional) weight loss compared to no weight change with risk estimates for MACE and mortality in primary prevention cohorts were included. A pre-defined protocol in accordance with the standards of quality for reporting meta-analysis of observational studies (MOOSE guidelines) was used. Random effects were used to summarize effects and heterogeneity was analyzed with I2. Subgroups were analyzed by age (&gt; 65) and comorbidities reported during follow-up. Results: Our search found 22.008 references and 13 studies met the selection criteria and were involved in the meta-analysis, including 142346 participants (51,3% men, age ranging from 42.2 to 75.3 years). Thirteen studies (25522 participants) reported intentional weight loss and 12 studies (25107 participants) reported non-intentional weight loss. Time of follow-up varied from 2 to 20 years. For intentional weight loss RR (95% CI) were 0.99 (0.92; 1.07) (I2 = 58.2%, p=0.003) and 1.03 (0.9; 1.15) (I2 = 0.0%, p=0.995) for all-cause and MACE, respectively. Subgroups by age of cohort and comorbidities did not change the estimates materially. For unintentional weight loss, RR (95% CI) were 1.25 (1.17; 1.34) (I2 = 70.4%, p=0.000) and 1.09 (0.96; 1.23) (I2 = 78.3%, p=0.001) for all-cause mortality and MACE, respectively. Subgroup analysis for participants with comorbidities yielded RR (95% CI) of 1.44 (1.31; 1.56) (I2 = 59.1%, p=0.012) and for participants older than 65 years, RR (95% CI) were 1.93 (1.65-2.22) (I2 = 0.0%, p=0.808) for all-cause mortality. Conclusion: Available observational evidence shows that unintentional weight loss significantly impacted on all-cause mortality in primary prevention cohorts, specially in aged populations. These findings should be accounted for when discussing the obesity paradox in general population.
Prognostic significance of leucocytosis in patients with metastatic non-small cell lung carcinoma.
Authors: Lamiae Amaadour, Zineb Benbrahim, Fatima Zahra Ziani, Lamiae Boudahna, Osmane Sy, Samia Arifi, Nawfel Mellas
Journal: Journal of Clinical Oncology (2014)

e19122 Background: Tumor-related leucocytosis is a paraneoplasic syndrome that is encountered occasionally in clinical course of patients with non small cell lung carcinoma (NSCLC). However, clinical characterization of this phenomenon has not been clarified. The aim of this study was to establish the correlation between leucocytosis and survival in moroccan patients with metastatic NSCLC. Methods: We retrospectively reviewed 207 cases of metastatic non small cell lung carcinoma diagnosed between January 2007 and December 2012 at the department of medical oncology, Hassan II University Hospital, Fez, Morocco. Complete blood counts were performed at the time of diagnosis and prior to treatment. Leucocytosis was defined as an absolute white blood cell count >10.000/mm³ with no evidence of infection. We used the Kaplan-Meier method and Cox model to estimate overall survival (OS) and progression free survival (PFS). Results: Median age was 57.8 ± 10 years. 85.5% of patients were men. 57.5% (107) of patients had leucocytosis at diagnosis with a mean of 15820/mm³. Leucocytosis was more frequently associated with poor performance status (2/4 on the ECOG scale) (p= 0.0001) and pleural effusion (p= 0.04). However, it was not correlated to age, body mass index, number of metastatic sites, bone metastasis, liver metastasis, hypercalcemia, anemia and hypoalbuminemia. 64.7% (134/207) of patients were treated with platinum based chemotherapy. The median duration of follow-up was 6.4 months (range: 1 - 29 months). On univariate analysis, Leucocytosis was significantly associated with shorter OS (mean: 5.7 vs 8.7 months, p =0,005). The PFS was not significantly different (mean: 5 vs 5.3 months, p=0.9). On multivariate analysis, leucocytosis was independent negative prognostic factor for OS. Conclusions: Our results suggest that leucocytosis is probably an indicator for poorer outcome in metastatic non small cell lung cancer. Prospective clinical trials are needed to confirm or deny the prognostic role of leucocytosis in this cancer.
Long-term versus short-term androgen deprivation combined with high-dose radiotherapy for intermediate and high-risk prostate cancer: A randomized controlled trial (DART01/05).
Authors: Almudena Zapatero, Araceli Guerrero, Xavier Maldonado, Ana Alvarez, Carmen González San Segundo, Maria Angeles Cabeza Rodriguez, Victor Macías, Francesc Casas, Agustí Pedro-Olivé, Ana Maria Boladeras, Carmen Martin de Vidales, Maria Luisa Vazquez de La Torre, Salvador Villà, Felipe A. Calvo
Journal: Journal of Clinical Oncology (2014)

5038 Background: Androgen deprivation (AD) combined with radiotherapy (RT) is an established treatment for locally advanced prostate cancer (PCa). However, the timing and optimal duration of AD associated with dose escalation RT remains controversial. This trial was designed to determine whether long-term AD (LTAD) is superior to short-term AD (STAD) when combined with high-dose radiotherapy (HDRT). Methods: Between 2006 and 2010, 362 assessable patients were enrolled. Eligible patients had cT1c-T3aN0M0 adenocarcinoma of prostate with intermediate risk (IR) and high risk (HR) factors according to 2005 NCCN criteria and PSA less than 100 ng/ml. All patients received 4 months of neoadjuvant and concomitant AD (STAD) + HDRT (median RT dose 78 Gy) before randomization to adjuvant gosereline for two years (LTAD). Stratification was performed according to risk group (IR versus HR). Study endpoints included biochemical-disease free survival (bDFS), metastasis free survival (MFS) and overall survival (OS). Results: Three hundred and fifty two patients (STAD =177, LTAD=175) were eligible with 57 months median follow-up.There were188 HR patients (STAD = 97, LTAD = 91) and 164 IR patients (STAD = 80, LTAD = 84) (p=0.669). Twenty-three patients in the STAD group and 7 patients in the LTAD group had biochemical failure according to Phoenix Consensus definition (p=0.003). Median OS has not been reached. At 5 years bDFS was significantly improved in the LTAD group (95.4%, 95% CI: 93.2-97.6), compared to the STAD group (86.1%, 95% CI: 83.5-88.7). Five-year MFS was 85.5% (95% CI: 82.9-88.1) for STAD and 93.2% (95% CI: 91.0-95.4) for LTAD, and OS was 88.8% (95% CI: 86.3-91.3) for STAD and 94.0% (95% CI: 91.9-96.1) for LTAD. Conclusions: The results of the present study indicate that the combination of HDRT with LTAD is superior to HDRT plus STAD in terms of bDFS. Further follow-up is needed to confirm these data and to assess the effect on MFS, OS and CSS. Clinical trial information: 2005-000417-36.
Mechanisms of PARP inhibitor resistance in cancer and insights into the DNA damage response
Authors: Paola Francica, Sven Rottenberg
Journal: Genome Medicine (2018)

Inhibitors of poly(ADP-ribose) polymerase (PARPi) have entered the clinic for the treatment of patients with cancers that lack homology-directed DNA repair, but drug resistance remains a clinical hurdle. Recent advances in the identification of PARPi resistance mechanisms have yielded a better understanding of DNA end protection and the relevance of endogenous poly(ADP-ribose) glycohydrolase, highlighting new vulnerabilities.
Colon cancer: Characteristics and survival rates in young versus old patients.
Authors: Shams Aziz Mistry, Harish Madala, Charles Chacko, Neha Jain, Jill Gernand, Madan L. Arora, Radhika Kakarala
Journal: Journal of Clinical Oncology (2014)

3585 Background: Colon cancer is detected at a later stage in younger patients (YP) (< 50 years) probably due to lack of screening in this age group. There has been an increased incidence of colon cancer (1.6%) in YP, but they are underrepresented in research studies. The aim of our study is to compare characteristics of colon cancer and survival outcome in YPs (18-49 years) vs older patients (>50) using the Surveillance, Epidemiology, and End Results (SEER) database. Methods: Using the SEER database (1991-2010), we reviewed patients > 18 years of age with colon cancer. Multivariate Cox regression analysis was used to evaluate risk adjusted outcomes and to predict the hazard of dying. Kaplan Meier method was used to estimate the survival function. Results: We included 375,443 patients in our study. YPs with colon carcinoma were more likely to be African American (15.7% vs 10.6%; p<0.001), Hispanic (13.5% vs 6.7%; p<0.001) and Asian (9.2% vs 6.3%; p<0.001) as compared to the older age group. YPs were more likely to present with distant metastasis (27.7% vs 19.1%; p<0.001) and had more poorly differentiated tumors (20.3 % vs 18.0%; p< 0.001). YPs also received more cancer directed surgery (92.6 % vs 91%; p<0.001) compared to their older counterparts. Five year survival was better for younger patients in all stages{table 1}. After controlling for gender, race, marital status, grade, stage, cancer specific surgery and post-operative radiation, we found that age is an independent predictor of death, and younger patients with colon cancer had a lower risk of dying (HR 0.767; p<0.001). Conclusions: Previous studies of YPs with colon cancer were found to have either equivalent or better survival in stages II and IV compared to older patients. Our study shows that young patients less than 50 years of age have more advanced stages of colon cancer at diagnosis but have better stage specific survival in all stages. Five-year survival rate for colon cancer patient. Stage of colon cancer Young (< 50 yrs) N=29,276 Older (≥ 50 years) N=346,167 P-value Localized 95.6% 91.1% <0.001 Regional 76.7% 72.8% <0.001 Distant 20.3% 16.8% <0.001 Unstaged 69.3% 50.4% <0.001
Effect of clonidine on proinflammatory cytokine levels in ex vivo human oral mucosa.
Authors: Pierre Attali, Lorraine Zakin, Boisnic Nicole, Veronique Trochon-Joseph, Caroline Lemarchand, Vanessa Roulet
Journal: Journal of Clinical Oncology (2014)

e20689 Background: A strategy for the attenuation of oral mucositis is inhibition of pro-inflammatory cytokines (PIC) which have been implicated in its pathogenesis. Clonidine, a α2 adrenergic agonist, has been observed to inhibit the expression and production of these cytokines, presumably through the NF-kB pathway. The objective of this study was to evaluate if clonidine could impede PIC in an ex vivo model of human oral mucosa. Methods: 5 mm3 biopsy samples of non-keratinized oral mucosa obtained from healthy volunteers were transferred onto permeable polycarbonate membrane transwells (12 mm diameter, 12 µm pore size). Saline (control group), Clonidine in 6 different concentrations (0,009, 0,03, 0,09, 0,3, 0,9, and 3 µg/ml), or clonidine + saline, was apically added every 2 hours for 6 doses and incubated for 10 hours. Substance P (SP) was added 10 hours after the first clonidine dose (except in clonidine + control) simultaneously with the last clonidine dose. Following an additional incubation for 24 hours, supernatants were removed and selected PIC levels were measured using ELISA (AbCys, France). Results: SP effected significant increases of TNF-α, IL-6, IL-1β and IL-10 in controls (Table). Clonidine impacted TNF-α levels in a dose-dependent manner with significant reductions noted at concentration of 0.9 µg/mL (p=0.01) and 3 µg/mL (p=p0.006), but not at lower concentrations. A similar, non-significant trend was noted for levels of IL-6 and IL-1β. Conclusions: SP produced expected increases in PIC in specimens of human oral mucosa. Clonidine effectively reduced TNF-α levels in a statistically significant way at the highest doses and modulated measurable IL-6 and IL-1β (not significant). These observations suggest a potential mechanism of action to explain the observed attenuation of OM in animal models and support further investigation into clonidine’s mechanism of action. Cytokine (pg/mg) Untreated control SP-treated control P value: SP vs untreated control Clonidine 0.9 g/mL Clonidine 3 µg/mL TNF-α 0.63±0.44 1.7±1.1 0.006 0.74±0.36 0.67±0.27 IL-10 0.21±0.16 0.96±0.59 0.012 0.37±0.23 0.41±0.47 IL-6 9.8±7.7 38.2±34.2 0.014 20±15 22.4±19.3 IL-1β 1.83±0.53 5.85±4.5 0.04 3.61±1.64 4.29±3.18
Abnormal screening mammogram follow-up: Improving time and timeliness benchmarks.
Authors: Seyed S. Pairawan, Kendra Anderson, Cherie Cora, Naveenraj Livingstone Solomon, Esther Lee, Won Bae, Sharon S. Lum
Journal: Journal of Clinical Oncology (2014)

6631 Background: Abnormal screening mammograms cause significant patient distress. Current benchmarks for timeliness of care for additional imaging after abnormal screening assess the time interval from screening to initial follow-up imaging. We sought to investigate the overall length of time required for imaging resolution after abnormal screening mammogram. Methods: We performed a retrospective review of women undergoing screening mammograms during a two month period at a tertiary-care institution. The main outcome measure was calendar days (d) between dates of screening mammogram and imaging resolution (final additional imaging or percutaneous biopsy). Results: From 1,133 sequential screening mammograms, 237 (20.9%) patients required at least one recall study. Median patient age was 55 years (28-92). Of patients requiring call back exams, 68.7% required only one recall; however, 23.6% required two; 6.3% required three; 0.8 % required four; and 0.04% required five. The overall median time for resolution of abnormal screening mammogram was 22 d (range 0-405). The time for resolution was significantly longer for women with a prior history of breast cancer than those without (35.5 d vs. 21 d, p=0.04), and in women with mass lesions compared to those with calcifications or a focal asymmetry (34 d vs. 22 d and 20 d, respectively, p=0.01). Time to resolution for patients requiring one recall was 14 d, two recalls was 42.5 d, three recalls was 49 d, four recalls was 68 d, and five recalls was 203 d (p<0.0001). There was no significant difference in time to resolution of abnormal screening mammogram based on patient age, race/ethnicity, BMI, insurance type, breast density, or individual radiologist. Conclusions: While most patients with abnormal mammograms had a single call back and resolution of imaging findings within two weeks of screening, a significant proportion of women required more prolonged imaging follow up. Patients with a history of breast cancer and those who present with mass lesions should be targeted for quality improvement. Benchmarks evaluating the overall time required for resolution of imaging findings may better represent the patient experience.