tbuckley/cabot-search huggingface dataset:
TPDC-FuHu chemotherapy for the treatment of recurrent metastatic brain tumors.
Authors: S E Kaba, A P Kyritsis, K Hess, W K Yung, R Mercier, S Dakhil, K A Jaeckle, V A Levin
Journal: Journal of Clinical Oncology (1997)

PURPOSE To evaluate a combination of thioguanine, procarbazine, dibromodulcitol, CCNU (CCNU), fluorouracil, and hydroxyurea (TPDC-FuHu), designed to improve the efficacy of CCNU, in the treatment of recurrent metastatic brain tumors. PATIENTS AND METHODS One hundred fifteen patients with progressive or recurrent metastatic brain tumors that failed to respond to surgery and/or radiation therapy were enrolled onto a multicenter prospective study between 1989 and 1995. Patients received TPDC-FuHu in a repeated cycle every 6 weeks until recurrence or until they completed six courses. RESULTS Ninety-seven patients were assessable at the end of the study. Forty-eight had lung cancer (39 non-small-cell [NSCLC] and nine small-cell [SCLC]), 28 had breast cancer, nine had melanoma, and 12 had adenocarcinoma of different origins (three colon, two kidney, one bladder, one stomach, and five of unknown origin). The response and stable disease (SD) rate (overall response rate) was 52%, 66%, 60%, and 22% in patients with NSCLC, SCLC, breast cancer, and melanoma, respectively. Median time to progression (MTP) was 12, 26, 12, and 6 weeks, respectively, for the four groups. Side effects were mild to moderate in the majority of patients. Severe myelosuppression (grade 4) occurred in only 11% of the patients. CONCLUSION TPDC-FuHu chemotherapy is an active treatment against recurrent brain metastases from breast cancer and SCLC, and to a lesser extent from NSCLC. This regimen is well tolerated and has acceptable toxicity.
Late-breaking abstract: Decreased sirtuin expression in squamous cell carcinoma compared to adenocarcinoma
Authors: Darja Isajeva, Sergejs Isajevs, Gunta Strazda, Ints Silins, Immanuels Taivans
Journal: European Respiratory Journal (2014)

Background. Sirtuin 1 (SIRT-1) is as an NAD+-dependent histone deacetylase. SIRT-1 has been shown to control cell cycle, proliferation and senescence, however the role of SIRT-1 in carcinogenesis is controversial.  The aim of our study was to compare the SIRT-1 expression in lung squamous cell carcinoma and adenocarcinoma.  Methods. 98 patients with lung nonsmall cell lung carcinoma were enrolled in the study. The control group consisted of 15 autopsy cases. The lung function testing was performed within one week before lung surgery. The SIRT-1 expression in lung cancer, peritumoral tissue and control group tissue was analyzed by immunohistochemistry and western blotting.  Results. Obtained results showed increased SIRT-1 expression in lung nonsmall cell carcinomas compared to control group (146 ± 112 vs. 3 ± 1 cells/mm2; p=0.007). Furthermore, the SIRT-1 expression was upregulated in peritumoral tissue compared to control group (57± 31 vs. 3 ± 1 cells/mm2; p=0.001). In addition, the SIRT-1 expression was higher in squamous cell carcinoma compared to adenocarcinoma (204 ± 143 vs. 95 ± 49 cells/mm2; p=0.04). Furthemore, in patients comorbid with COPD and lung cancer, the SIRT-1 expression tended to be decreased compared to cancer patients without COPD. The positive correlation between disease stage and SIRT-1 expression was observed.  Conclusion. Lung cancer is characterized by upregulated SIRT-1 expression, which is significantly increased in squamous cell carcinoma compared to adenocarcinoma and it correlates with disease stage.
Correlation of Glycolytic and Respiratory Events after Addition of a Small Amount of Glucose to Ehrlich Ascites Carcinoma
Authors: Elmon L. Coe
Journal: Cancer Research (1966)

The accumulations of lactate, pyruvate, and several phosphorylated compounds were measured in a suspension containing 1.8 volumes % of Ehrlich ascites tumor cells in 54 mm phosphate (pH 7.35) at 30°C after addition of 0.08 mm glucose. The ATP[2][1] level increased from 0.3 to 2.1 µmoles/ml of cells during a period of 120 sec. All measured phosphorylated glycolytic intermediates rose to maxima and then declined to the endogenous level by 120–150 sec except phosphopyruvate, which exhibited a distinct decline during the 1st 30 sec and then rose again.

The rate of oxygen consumption, as estimated with a bare, vibrating-reed, platinum-electrode polarograph, decreased during the 1st 45 sec, remained low until 150 sec, and then increased to a plateau that was reached by 270 sec. Additional experiments confirmed that recovery of respiration from inhibition lagged behind the cessation of glycolysis.

The sum of glycolytic and respiratory ATP synthesis (estimated by assuming complete coupling) gave a curve that rose during the 1st 30 sec, fell sharply between 90 and 150 sec, and rose again between 150 and 270 sec. The results are interpreted to mean that glycolytically synthesized ATP is more immediately available for cellular maintenance than oxidatively generated ATP.

 [1]: #fn-2
CASC15-S Is a Tumor Suppressor lncRNA at the 6p22 Neuroblastoma Susceptibility Locus
Authors: Mike R. Russell, Annalise Penikis, Derek A. Oldridge, Juan R. Alvarez-Dominguez, Lee McDaniel, Maura Diamond, Olivia Padovan, Pichai Raman, Yimei Li, Jun S. Wei, Shile Zhang, Janahan Gnanchandran, Robert Seeger, Shahab Asgharzadeh, Javed Khan, Sharon J. Diskin, John M. Maris, Kristina A. Cole
Journal: Cancer Research (2015)

Abstract Chromosome 6p22 was identified recently as a neuroblastoma susceptibility locus, but its mechanistic contributions to tumorigenesis are as yet undefined. Here we report that the most highly significant single-nucleotide polymorphism (SNP) associations reside within CASC15, a long noncoding RNA that we define as a tumor suppressor at 6p22. Low-level expression of a short CASC15 isoform (CASC15-S) associated highly with advanced neuroblastoma and poor patient survival. In human neuroblastoma cells, attenuating CASC15-S increased cellular growth and migratory capacity. Gene expression analysis revealed downregulation of neuroblastoma-specific markers in cells with attenuated CASC15-S, with concomitant increases in cell adhesion and extracellular matrix transcripts. Altogether, our results point to CASC15-S as a mediator of neural growth and differentiation, which impacts neuroblastoma initiation and progression. Cancer Res; 75(15); 3155–66. ©2015 AACR.
Progress in the Implementation of NCCN Guidelines for Distress Management by Member Institutions
Authors: Kristine A. Donovan, Paul B. Jacobsen
Journal: Journal of the National Comprehensive Cancer Network (2013)

A 2005 survey of NCCN Member Institutions was among the first studies to evaluate the extent to which key elements of the NCCN Clinical Practice Guidelines in Oncology for Distress Management were being implemented as part of routine clinical practice. This study seeks to characterize current implementation of the guidelines by NCCN Member Institutions 7 years after the original study. Institutional representatives appointed to the NCCN Distress Management Panel were asked to complete an online survey in June 2012. The survey was similar to the 2005 survey, except that it solicited additional details about screening procedures. The survey was completed by representatives from 20 of 22 NCCN Member Institutions (91%). (Note: In this calculation, 1 consortium cancer cancer was counted as 2 NCCN Member Institutions.) Responses indicate that routine screening for distress is being conducted at 70% of institutions, with 25% screening inpatients and 60% screening outpatients. Among institutions screening outpatients, 50% screen all outpatients and 50% screen only certain subgroups of outpatients. In terms of method, 85% of institutions conducting screening use a patient self-report measure either alone or in combination with an interview; the Distress Thermometer is used at 59% of institutions that use a self-report measure. Findings show modest progress since 2005 in implementing guideline recommendations regarding distress screening, with a 7% increase in institutions conducting any routine screening and a 10% increase in institutions screening all outpatients routinely. Greater progress is evident in the use of self-report measures as part of screening, with a 23% increase in their use alone or in combination with an interview.
Adjuvant CYVADIC chemotherapy for adult soft tissue sarcoma--reduced local recurrence but no improvement in survival: a study of the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group.
Authors: V Bramwell, J Rouesse, W Steward, A Santoro, H Schraffordt-Koops, J Buesa, W Ruka, J Priario, T Wagener, M Burgers
Journal: Journal of Clinical Oncology (1994)

PURPOSE To evaluate the benefit of adjuvant chemotherapy in adult patients with soft tissue sarcomas. The principal end points were freedom from local recurrence and/or metastases and overall survival. PATIENTS AND METHODS Between January 1977 and June 1988, 468 patients entered this randomized study and 317 were considered eligible. Following complete surgical resection with or without radiotherapy, outcome in 145 eligible patients receiving cyclophosphamide 500 mg/m2 intravenously (IV) bolus on day 1, vincristine 1.4 mg/m2 IV bolus on day 1, doxorubicin (Adriamycin; Adria Laboratories, Columbus, OH) 50 mg/m2 IV bolus on day 1, and dacarbazine (DTIC) 400 mg/m2 by 1-hour infusion on days 1 to 3 (CYVADIC) cycles repeated every 28 days for eight courses was compared with that in 172 control patients. RESULTS With a median follow-up duration of 80 months (range, 39 to 165), actuarial percentage survival figures at 7 years were compared. Relapse-free survival rates were higher for CYVADIC, 56% versus 43% (P = .007), and local recurrence was significantly reduced in the CYVADIC arm at 17% versus 31% (P = .004). In contrast, distant metastases occurred with similar frequency in both arms, 32% for CYVADIC versus 36% for control patients (P = .42), and overall survival rates were not significantly different at 63% versus 56% (P = .64). A reduction in local recurrence was only apparent in the group of head, neck, and trunk sarcomas (P = .002), but not in limb tumors (P = .31). CONCLUSION Adjuvant chemotherapy with CYVADIC cannot be recommended outside the context of a clinical trial. Experience from this study has been used to plan a trial of neoadjuvant chemotherapy with doxorubicin/ifosfamide, which is currently in progress.
Phase II Comparator Study of Oral Versus Intravenous Topotecan in Patients With Chemosensitive Small-Cell Lung Cancer
Authors: Joachim von Pawel, Ulrich Gatzemeier, Jean-Louis Pujol, Lionel Moreau, S. Bildat, Malcolm Ranson, Gary Richardson, Claus Steppert, Alain Rivière, Ina Camlett, Stephen Lane, Graham Ross
Journal: Journal of Clinical Oncology (2001)

PURPOSE: Topotecan, administered intravenously, is active in small-cell lung cancer (SCLC). In this study, the comparability of oral topotecan to IV topotecan was investigated. PATIENTS AND METHODS: Patients with SCLC that had relapsed 90 days or more after cessation of initial chemotherapy were randomized to receive either oral topotecan (Hycamtin) 2.3 mg/m 2 /d × 5 (52 patients) or IV topotecan 1.5 mg/m 2 /d × 5 (54 patients), every 21 days. RESULTS: Response rates in this phase II randomized study were 23% (12/52) in the oral topotecan arm and 15% (8/54) in the IV topotecan arm. All radiological responses were confirmed by an independent radiologist. Median survival was 32 weeks (oral) and 25 weeks (IV). Good symptom control, defined as sustained improvement or no deterioration, was evident in both treatment groups. Topotecan was generally well tolerated, with myelosuppression being the major toxicity. Grade 4 neutropenia occurred in 35.3% of patients on oral topotecan and in 67.3% of patients on IV topotecan, which was statistically significant (P = .001). Fever/infection more than or equal to grade 2 associated with grade 4 neutropenia, together with sepsis, occurred in only 5.1% of courses (oral) and 3.3% of courses (IV). Non-hematological toxicity consisted mainly of vomiting (oral: 36.5% of patients; IV: 31.5% of patients) and nausea (oral: 26.9% of patients; IV: 40.7% of patients). CONCLUSION: This study found oral topotecan to be similar in efficacy to IV topotecan in the treatment of patients with relapsed SCLC, sensitive to first-line chemotherapy, with less grade 4 neutropenia and greater convenience of administration.
Surgeon is struck off for behaviour "fundamentally incompatible" with being a doctor
Authors: C. Dyer
Journal: BMJ (2015)

A general surgeon who botched a cancer operation, failing to remove an easily palpable tumour and leaving the patient with a distorted chest, has been struck off the medical register after persistently refusing to acknowledge his mistakes.

Mutasim Mohammed failed to show any insight into his shortcomings or to provide evidence of remediation despite two 12 month periods of suspension, a Medical Practitioners Tribunal Service panel concluded.

He was originally suspended in December 2012 for working beyond the limits of his surgical competence in performing breast cancer surgery when he had little …
Chemokine up-regulation in SARS-coronavirus–infected, monocyte-derived human dendritic cells
Authors: Helen K. W. Law, Chung Yan Cheung, Hoi Yee Ng, Sin Fun Sia, Yuk On Chan, Winsie Luk, John M. Nicholls, J. S. Malik Peiris, Yu Lung Lau
Journal: Blood (2005)
Cameron's pledge on seven day working is branded "empty headline grabbing"
Authors: G. Iacobucci
Journal: BMJ (2015)

Prime Minister David Cameron has reiterated his pledge to implement full seven day working in the NHS in his first major speech since the general election.

In a speech at a health centre in the West Midlands the re-elected prime minister said that his government would expand access to routine GP and hospital care to allow patients to receive the same service at weekends as they did from Monday to Friday.1 He said that the transformation would be funded from the £8bn (€11bn; $13bn) a year his party had pledged to invest by the end of the parliament to support NHS England’s Five Year Forward View .

But doctors’ leaders said that this funding would be enough only to keep current NHS services running and would not be enough for an expansion to full seven day working. The BMA said that the plans as they stood were uncosted and “empty headline …
Receptor interacting protein kinase 1 mediates murine acetaminophen toxicity independent of the necrosome and not through necroptosis
Authors: Lily Dara, Heather Johnson, Jo Suda, Sanda Win, William Gaarde, Derick Han, Neil Kaplowitz
Journal: Hepatology (2015)

Although necrosis in the acetaminophen (APAP) model is known to be regulated by c‐Jun NH2‐terminal kinase (JNK) through interaction with mitochondria, the role of necroptosis through receptor‐interacting proteins 1 and 3 (RIPK1 and RIPK3) has also been suggested. Our aim was to determine the relationship between these two mechanisms of cell death. To verify the participation of RIPK1, we used antisense knockdown and confirmed protection comparable to the RIPK1 inhibitor, necrostatin, in vivo and in vitro . However, we found no evidence that RIPK3 is expressed in primary mouse hepatocytes under basal conditions or after APAP and RIPK3 −/− mice were not protected. RIPK3 was exclusively expressed in nonparenchymal cells. RIPK1 knockdown protected RIPK3 −/− mice to the same extent as wild‐type mice, underscoring the independent role of RIPK1. We confirmed that necroptosis is not involved in APAP toxicity by using mixed lineage kinase domain‐like protein (MLKL) knockout mice, which were not protected from APAP. Next, we addressed whether there is interplay between RIPK1 and JNK. RIPK1 knockdown decreased the level of JNK activation and translocation to mitochondria and abrogated subsequent translocation of dynamin‐related protein 1 (Drp1). Interestingly, APAP induced translocation of RIPK1 to mitochondria, which was unaffected by knockdown of the mitochondrial JNK docking protein, Sh3 homology 3 binding protein 5 (Sab). Conclusion : RIPK1 participates in APAP‐induced necrosis upstream of JNK activation whereas RIPK3 and MLKL are dispensable, indicating that necroptosis does not contribute to APAP‐induced necrosis and RIPK1 has a unique, independent role.(H epatology 2015;62:1847–1857)
Risk Factors for Fibrocystic Breast Disease and Its Histopathologic Components&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: G S Berkowitz, J L Kelsey, V A LiVolsi, T R Holford, M J Merino, S Ort, T Z O'Connor, C White
Journal: JNCI Journal of the National Cancer Institute (1985)

The relationship between various sociodemographic, reproductive, and other factors to the occurrence of fibrocystic breast disease was evaluated in a case-control study undertaken at five Connecticut hospitals from 1979 to 1981. The study groups comprised 590 women with biopsy-proven fibrocystic breast disease and 1,018 women with other surgical conditions. Among the premenopausal women, multivariate analysis suggested that high socioeconomic status, Jewish religion, low parity, a history of benign breast disease, a history of breast cancer in the mother or a sister, and low Quetelet index were associated with increased odds ratios (OR) for fibrocystic breast disease. Similar analysis for the postmenopausal women revealed increased OR for women with high socioeconomic status, a late age at menopause, and a history of benign breast disease. Current smokers as well as those who had had a tubal sterilization had significantly reduced odds of fibrocystic disease. There was no convincing evidence of linear trends according to degree of epithelial atypia for any of the variables considered. Although some variation in the OR emerged in the analysis according to selected histologic components, the results provided little evidence that women with biopsy specimens exhibiting gross cysts, sclerosing adenosis, papillary hyperplasia, or papillomatosis showed epidemiologic similarities with breast cancer patients.
Werner protein stimulates topoisomerase I DNA relaxation activity.
Authors: Jean-Philippe Laine, Patricia L. Opresko, Fred E. Indig, Jeanine A. Harrigan, Cayetano von Kobbe, Vilhelm A. Bohr
Journal: Cancer Research (2003)

Werner syndrome (WS) is a human premature aging disorder characterized by the early onset of age-related clinical features and an elevated incidence of cancer. The Werner protein (WRN) belongs to the RecQ family of DNA helicases and is required for the maintenance of genomic stability in human cells. Potential cooperation between RecQ helicases and topoisomerases in many aspects of DNA metabolism, such as the progression of replication forks, transcription, recombination, and repair, has been reported. Here, we show a physical and functional interaction between WRN and topoisomerase I (topo I). WRN colocalizes and interacts directly with topo I. WRN stimulates the ability of topo I to relax negatively supercoiled DNA and specifically stimulates the religation step of the relaxation reaction. Moreover, cell extracts from WS fibroblasts exhibit a decrease in the relaxation activity of negatively supercoiled DNA. We have identified two regions of WRN that mediate functional interaction with topo I, and they are located at the NH(2) and COOH termini of the WRN protein. In a reciprocal functional interaction, topo I inhibits the ATPase activity of WRN. Our data provide new insight into the interrelationship between RecQ helicases and topoisomerases in the maintenance of genomic integrity and prevention of tumorigenesis.
Long-Term Outcome of Patients With American Joint Committee on Cancer Stage IIB Extremity Soft Tissue Sarcomas
Authors: Jason B. Fleming, Russell S. Berman, Su-Chun Cheng, Nancy P. Chen, Kelly K. Hunt, Barry W. Feig, Paula M. Respondek, Alan W. Yasko, Alan Pollack, Shreyaskumar R. Patel, Michael A. Burgess, Nicholas E. Papadopoulos, Carl Plager, Gunar Zagars, Robert S. Benjamin, Raphael E. Pollock, Peter W.T. Pisters
Journal: Journal of Clinical Oncology (1999)

It has been suggested that patients with small (< 5 cm), high-grade extremity soft tissue sarcomas (STS) have an excellent overall prognosis and, consequently, may not require adjuvant therapies.A comprehensive review of all patients with extremity STS treated at a tertiary care cancer hospital over a 9-year period (January 1984 to December 1992) was performed. Prognostic factors, treatment data, and long-term outcome were evaluated in the subset of 111 patients with American Joint Committee on Cancer stage IIB (G3/4, T1a/b) disease.The median tumor size was 3.0 cm (range, 0.6 to 4.9 cm), and 55 tumors (50%) were deep in location. All patients underwent surgical resection; 68 (61%) received pre- or postoperative radiotherapy, and 32 (29%) received doxorubicin-based chemotherapy. The median follow-up was 76 months. Forty patients (36%) experienced 59 recurrences. First recurrences occurred at local, regional, and distant sites in 21, five, and 14 patients, respectively. The 5-year actuarial local recurrence-free, distant recurrence-free, disease-free, and overall survival rates were 82%, 83%, 68%, and 83%, respectively. The presence of a microscopically positive surgical margin was an independent adverse prognostic factor for both local recurrence (relative risk [RR] = 3.75; 95% confidence interval [CI], 1.25 to 11.25; P =.02) and disease-free survival (RR = 2.57; 95% CI, 1.33 to 4.98; P =.005).Event-free outcome for this subset of patients with high-grade STS does not seem as favorable as previously reported by other investigators. Patients who undergo maximal surgical resection with microscopically positive margins represent a subset of T1 STS patients who warrant consideration for adjuvant therapies.
Prognostic factors analysis of patients with acute exacerbation of idiopathic interstitial pneumonias treated by polymyxin B hemoperfusion
Authors: Keiji Oishi, Keisuke Aoe, Yoriyuki Murata, Kenji Sakamoto, Takashi Ohfuji, Wataru Kotoku, Yoshiko Ogata, Tsuneo Matsumoto, Hiroshi Ueoka, Yusuke Mimura
Journal: European Respiratory Journal (2013)

Background:  Acute exacerbations of idiopathic interstitial pneumonias (AE-IIPs) are episodes of acute respiratory worsening with high mortality. Direct hemoperfusion with polymyxin B-immobilized fiber column (PMX-DHP), which was established in Japan for treatment of sepsis, has been shown to improve the respiratory status of patients with ARDS. Recent reports have suggested beneficial effects of PMX-DHP on oxygenation in AE-IIPs as well. Here we aimed to investigate the outcome and prognostic factors in patients with AE-IIPs treated by PMX-DHP.   Methods:  We retrospectively compared 23 AE-IIP patients treated by steroid pulse therapy and PMX-DHP (PMX-DHP group) with 16 AE-IIP patients by steroid pulse therapy (control group). PMX-DHP was conducted once daily for 6 hours, 2 successive days.   Results:  The 90-day survival rate was significantly higher in PMX-DHP group (52.2%) than in control group (18.8%). The median survival time was 192 days for PMX-DHP group vs 21.5 days for control group (log rank test P value = 0.0134). Univariate analysis showed that age, duration of AE-IIP till PMX-DHP and P/F ratio were significant predictors of survival. Using multivariate analysis age (p=0.006,HR=19.65) and the duration (p=0.004,HR=22.72) were found to be independent prognostic factors.   Conclusion:  This case-control study suggests that PMX-DHP therapy improves survival in AE-IIP patients. The prognostic potential of age and duration of AE-IIP may be useful for the selection of patients who benefit from PMX-DHP.