tbuckley/cabot-search huggingface dataset:
Survival differences between preoperative and postoperative radiation in esophageal cancer treated with combined modality therapy: A SEER analysis.
Authors: Andrzej Pawel Wojcieszynski, Abigail Berman Milby, John Peter Plastaras, James M. Metz, Smith Apisarnthanarax
Journal: Journal of Clinical Oncology (2012)

78 Background: The effect of radiation therapy (RT) sequencing with surgery on clinical outcomes for locally advanced esophageal cancer patients is unclear. We hypothesized that RT given prior to surgery has superior survival outcomes compared to RT delivered after surgery. Methods: Patients with the following inclusion criteria were identified within 17 Surveillance, Epidemiology, and End Results (SEER) registries from 1988-2006: adenocarcinoma or squamous cell carcinoma of the esophagus, esophagectomy, and RT. Data on demographics, tumor characteristics, and survival outcomes were extracted and compared between patients receiving preoperative and those receiving postoperative RT. Cox regression univariate and multivariate analyses were performed to identify parameters that were associated with cause-specific (CSS) and overall survival (OS). Results: A total of 2,579 patients met the defined criteria. Of these patients, 1,689 received preop RT and 890 received postop RT. Patients receiving preop RT compared to postop RT had improved 5-yr CSS (41% vs. 31%, p&lt;0.0001) and OS (33% vs. 23%, p&lt;0.0001). On univariate analysis, RT sequence, histology, T stage, nodal status, number lymph nodes examined, age, gender, marital status, race, and county income were significant independent predictors of OS. On multivariate analysis ( table ), preop RT continued to remain statistically significant for OS (HR 0.88; p = 0.034). Conclusions: Preoperative RT is associated with superior overall and cause-specific survival compared to postoperative RT and should be the preferred approach in combination with surgery for locally advanced esophageal cancer. [Table: see text]
Marine Mollusk‐Derived Agents with Antiproliferative Activity as Promising Anticancer Agents to Overcome Chemotherapy Resistance
Authors: Maria Letizia Ciavatta, Florence Lefranc, Marianna Carbone, Ernesto Mollo, Margherita Gavagnin, Tania Betancourt, Ramesh Dasari, Alexander Kornienko, Robert Kiss
Journal: Medicinal Research Reviews (2016)

The chemical investigation of marine mollusks has led to the isolation of a wide variety of bioactive metabolites, which evolved in marine organisms as favorable adaptations to survive in different environments. Most of them are derived from food sources, but they can be also biosynthesized de novo by the mollusks themselves, or produced by symbionts. Consequently, the isolated compounds cannot be strictly considered as "chemotaxonomic markers" for the different molluscan species. However, the chemical investigation of this phylum has provided many compounds of interest as potential anticancer drugs that assume particular importance in the light of the growing literature on cancer biology and chemotherapy. The current review highlights the diversity of chemical structures, mechanisms of action, and, most importantly, the potential of mollusk-derived metabolites as anticancer agents, including those biosynthesized by mollusks and those of dietary origin. After the discussion of dolastatins and kahalalides, compounds previously studied in clinical trials, the review covers potentially promising anticancer agents, which are grouped based on their structural type and include terpenes, steroids, peptides, polyketides and nitrogen-containing compounds. The "promise" of a mollusk-derived natural product as an anticancer agent is evaluated on the basis of its ability to target biological characteristics of cancer cells responsible for poor treatment outcomes. These characteristics include high antiproliferative potency against cancer cells in vitro, preferential inhibition of the proliferation of cancer cells over normal ones, mechanism of action via nonapoptotic signaling pathways, circumvention of multidrug resistance phenotype, and high activity in vivo, among others. The review also includes sections on the targeted delivery of mollusk-derived anticancer agents and solutions to their procurement in quantity.
The effects of clinical trials on improving breast cancer care at a single institution.
Authors: W. C. Dooley, J. Parker, J. Bong
Journal: Journal of Clinical Oncology (2011)

198 Background: We reported in 2011 at the Society of Surgical Oncology a 19 year retrospective at a single academic institution which identified practice differences between surgical oncologists and general surgeons which were associated with a significant survival advantage. Clinical trial participation was much higher amongst patients treated by a surgical oncologist. Methods: This is an IRB approved, retrospective review of all breast cancer patients receiving primary treatment at a single institution from 1/1/2001 to 12/31/2008. Details of pathology, surgical therapy, chemotherapy, hormonal therapy and radiation therapy were compared between patients participating in clinical trials and those not participating. The specific trials were segregated as to type (tissue banking, therapeutic, prevention, etc.) to understand differential effects if any between type of trial participation. Results: During the time period, there were 1220 patients who received primary breast cancer treatment at this institution. The mean age was 55.6 and mean follow-up &gt;40 months. Stage distribution was stage 0 - 16.8%, Stage 1 - 26.6%, Stage 2 - 33.1%, Stage 3 - 15.9%, and Stage 4 - 6.1%. Patients participating in any clinical trial numbered 468 and 752 participated in no clinical trials. Overall survival (clinical trial 98.8% vs. not in clinical trial 75.7%; p&lt;0.0001). Overall the use of breast conservation was more likely in clinical trial participants (54.3% vs. 44.4%; p&lt;0.0001). The completion of chemotherapy was more likely in clinical trial participants (52.4% vs. 49.5%; p=0.02).The successful completion of systemic therapies (chemo and hormonal) was more likely also (71.4% vs. 64.0%; p=0.009). The type of trial (tissue banking vs. therapeutic) had no effect on improved outcomes. Overall the best predictor of better outcomes was to be treated by a high volume clinical trial enrolling physician. Conclusions: High volume clinical trial enrollment is associated with the best overall treatment outcomes in breast cancer whether trials are directly related to therapeutic changes or not. Each individual in the breast center treating team can have dramatic effect on outcomes by improving their clinical trial enrollment and participation.
Integrated support in neoplastic patient and family: experience of molise in ccm 2012 project
Authors: F. Carrozza, C. Spina, M.A. Viglione, C. Franchella, M. Bellomo, P. Antonecchia, T. Manfredi Selvaggi, M. Musacchio, G. Antuzzi, M. Specchia, S. Piano, A. Silvestri, G. Giglio, G. Fabrizio, L. Di Lullo
Journal: Annals of Oncology (2015)
The Impact of HCV Viremia on the Tempo of Engraftment and the Incidence of Acute and Chronic Graft Versus Host Disease (GVHD) As Well As Sinusoidal Obstruction Syndrome (SOS): A Single Centre Experience of 332 Patients Following Allogeneic Peripheral Blood Stem Cells Transplantation (PBSCT)
Authors: Omar Fahmy, Gamal El Din M Fathy, Alaa M Elhaddad, Almetwaly M. Sultan, Shimaa Ibrahim, Mahmoud Bokhary, Yasser Elnahass, Mohamed Talaat, Rafaat MS Abdelfattah, Mohamed A. Samra, Hossam K Mahmoud
Journal: Blood (2016)
Use of endoscopic ultrasound to reduce the need for SpyGlass cholangioscopy and improve its diagnostic yield.
Authors: Nam Q. Nguyen
Journal: Journal of Clinical Oncology (2012)

169 Background: The accuracy of SpyGlass cholangioscopy (SGC) guided biopsy is only modest (60%) due to extrinsic lesion causing ductal stricture. Endoscopic ultrasound (EUS) can visualise the biliary tree and acquire tissue via fine needle aspiration (FNA). The aim is to evaluate the utility of EUS-FNA in patients who were referred for SGC for biliary strictures. Methods: The clinical impact of EUS-FNA was prospectively examined in 17 patients (10M; 56.2±1.9 yrs) who were referred for SGC to investigate difficult biliary strictures over 15 months. All patients had endoscopic retrograde cholangiography and biliary stenting with negative ductal brushing. Any mass lesion(s) or pathological node(s) found on EUS were biopsied. SGC and ductal biopsy were only performed if EUS-FNA could not provide a diagnosis. The results were compared to the surgical specimens or the positive histo-cytological findings from biopsies. Results: EUS examination was able to identify all ductal or peri-ductal abnormalities responsible for the biliary strictures, with sonographic diagnoses of cholangiocarcinoma (n=10), autoimmune pancreatitis (n=2), choledochocyst related stricture (1); pancreatic cancer (n=1), gallbladder cancer (n=1), Mirrizi’s syndrome (n=1) and colorectal metastasis (n=1). EUS-FNA was possible in 13 (76%) cases and provided tissue diagnosis in 9 (59%) patients, which can potentially avoid the need for SGC and cost saving of ~$ 48,000. SGC examination was successful in 7/8 patients, with 100% correct tissue diagnosis from Spybite biopsy (4 cholangio-carcinomas, 1 autoimmune pancreatitis, 1 biliary villous adenoma, 1 hepatoma, 1 high grade dysplastic choledochocyst). SpyScope intubation was not possible in a patient with long-standing primiary sclerosing cholangitis who had tight stricturing of the entire extra-hepatic duct. Overall, tissue diagnosis was established in 94% (16/17) patients. Conclusions: EUS able to detect 100% ductal or peri-ductal abnormalities responsible for biliary strictures referred for SGC. Together with FNA, EUS provides correct diagnosis and avoids the need for SGC in 59% of cases, resulting in significant cost saving but also improving the yield of SpyGlass guided biopsy.
Comparative Efficacy Among 3rd Line Post-Imatinib Chronic Phase-Chronic Myeloid Leukemia (CP-CML) Patients after Failure of Dasatinib or Nilotinib Tyrosine Kinase Inhibitors
Authors: Jeffrey H. Lipton, Dhvani Shah, Vanita Tongbram, Manpreet K Sidhu, Hui Huang, Lisa J McGarry, Stephanie Lustgarten, Neil Hawkins
Journal: Blood (2014)
Neoadjuvant cisplatin and doxorubicin in locally advanced breast cancer.
Authors: S. A. Gurchani, A. I. Masood, A. Anwer, A. Mateen
Journal: Journal of Clinical Oncology (2011)

e11526 Background: Breast cancer is the most common malignancy in females. Most of the patients present in advanced stage of the disease. Primary therapy in these patients remains surgery but it is usually not possible due to advanced nature of presentation in our population. Data is deficient for most commonly used chemotherapeutic drugs, cisplatin and doxorubicin, to be used as neo-adjuvant chemotherapy in this set of patients. We evaluated the role of cisplatin and doxorubicin in locally advanced breast cancer (LABC). Methods: In this retrospective study we reviewed fifty LABC patients treated with cisplatin (60 mg/m2) and doxorubicin (50 mg/m2). The patients were evaluated for whether surgery was possible in these patients. The primary end point was to assess the response to therapy and whether surgical resection was possible. Results: Patients received three to six cycles (Median=5) of doxorubicin and cisplatin chemotherapy. All patients tolerated chemotherapy regimen well with no documented chemotherapy related mortality. Four (8%) patients showed complete response, thirty four (68%) patients showed partial response, five (10%) had stable disease and seven (14%) patients had disease progression. Thirty seven (72%) patients underwent surgery after initial chemotherapy. Thirty four (92%) of them underwent modified radical mastectomy and toilet mastectomy was done in three (8%) patients. Thirteen (26%) patients were further treated by other chemotherapy regimen. Thirty three (89%) of the patients having done surgery also received locoregional radiation therapy. Five patients (22%) out of twenty three tested were positive for hormone receptor and received tamoxifen after completion of radiotherapy. Conclusions: Neo-adjuvant chemotherapy with combination of doxorubicin and cisplatin seems to be effecting in down staging the LABC and rendering surgery possible. A randomized trial comparing with standard regimen will be more appropriate to define the optimum use of this regimen in routine practice.
Exomic sequencing of pancreatic neuroendocrine tumors: Detection of alterations in chromatin remodeling and mTOR pathway genes.
Authors: L. A. Diaz, Y. Jiao, C. Shi, B. H. Edil, R. de Wilde, D. S. Klimstra, A. Maitra, L. H. Tang, A. L. Blackford, V. Velculescu, B. Vogelstein, K. W. Kinzler, R. H. Hruban, N. Papadopoulos
Journal: Journal of Clinical Oncology (2011)

10501 Background: Pancreatic Neuroendocrine Tumors (PanNETs) are a rare but clinically important form of pancreatic neoplasia but relatively little is known about the molecular genetics of this disease. Methods: To explore the genetic basis of PanNETs, we determined the exomic sequences of ten non-familial PanNETs and then screened the most commonly mutated genes in 58 additional PanNETs. Results: We found frequently mutated genes implicated in chromatin remodeling: 44% of the tumors had somatic inactivating mutations in MEN-1, which encodes menin, a component of a histone methyltransferase complex; and 43% had mutations in genes encoding either of the two subunits of a transcription/chromatin remodeling complex consisting of DAXX (death-domain associated protein) and ATRX (alpha thalassemia/mental retardation syndrome X-linked). In a multivariate analysis adjusting for WHO classification, mutations in the MEN1 (HR 0.30; 95% CI 0.1-0.9; p=0.03) and DAXX/ATRX (HR 0.23; 95% CI 0.07-0.75; p=0.02) genes, alone or in combination (HR 0.11; 95% CI 0.02-0.55; p=0.01), were associated with better prognosis. Interestingly, tumors without mutations in MEN1 or DAXX/ATRX were primarily from patients with PanNETs localized to the pancreas (p=0.006). We also found mutations in genes in the mTOR (mammalian target of rapamycin) pathway in 14% of the tumors that included mutations in PIK3CA, PTEN and TSC2. Conclusions: Taken together, these findings could potentially be used to stratify patients with PanNETs and help determine which patients may benefit from treatment with mTOR inhibitors.
Early Clearance of Peripheral Blood Blasts but Not White Blood Cells Is a Powerful Prognostic marker for complete Response and Overall Survival in Patients with Acute Myeloid Leukemia (AML) receiving Induction Chemotherapy
Authors: Alfonso Quintas-Cardama, Hagop Kantarjian, Guillermo Garcia-Manero, Mark Brandt, Sherry Pierce, Gautam Borthakur, Jorge E. Cortes
Journal: Blood (2011)
The Identification of Novel Therapies for the Treatment of Follicular Dendritic Cell Sarcoma
Authors: Bo Wang, Liang Zhang, Lan Pham, Wenjing Tao, Hui Zhang, Jingmeng Xie, Wendy Chen, Qingqing Cai, Dehui Zou, Donglu Zhao, Xiuhua Sun, Rong Liang, Jack Wang, Krystle Nomie, Nathan Fowler, Michael Wang
Journal: Blood (2015)
What if consciousness has no function?
Authors: Susan Blackmore
Journal: Behavioral and Brain Sciences (2016)

Abstract An implicitly dualist or Cartesian materialist theory of consciousness is proposed without citing the many well-known problems with such theories. A function for consciousness is proposed with no reference to the possibility that “consciousness itself” has no function of its own. The theory builds on proposed “subset consensus” and “integration consensus” when in the literature there is no such consensus on these issues.
US to ban smoking in public housing
Authors: Owen Dyer
Journal: BMJ (2016)

The US government will ban smoking in public housing, said Housing and Urban Development (HUD) secretary Julian Castro.

The new rule will affect about 1.2 million homes. It applies only to those living in publicly owned housing, not to those who pay private rent with help from HUD subsidies. The ban will come into force on 1 January 2017, but local housing authorities have up to 18 months to comply.

Smoking is already banned in all public indoor areas in HUD housing, such as lobbies and stairways. The new rule bans cigarette, pipe, cigar, hookah, and other combustible tobacco use …
Combined immunodeficiency with severe inflammation and allergy caused by ARPC1B deficiency
Authors: Taco W. Kuijpers, Anton T.J. Tool, Ivo van der Bijl, Martin de Boer, Michel van Houdt, Iris M. de Cuyper, Dirk Roos, Floris van Alphen, Karin van Leeuwen, Emma L. Cambridge, Mark J. Arends, Gordon Dougan, Simon Clare, Ramiro Ramirez-Solis, Steven T. Pals, David J. Adams, Alexander B. Meijer, Timo K. van den Berg
Journal: Journal of Allergy and Clinical Immunology (2016)
The Proteasome Inhibitor Bortezomib Simultaneously Enhances NK Cell Tumor Cytotoxicity While Paradoxically Reducing Antigen Specific T-Cell Tumor Cytotoxicity.
Authors: Andreas Lundqvist, Sheila Rao, Maria Berg, Aleah Smith, Su Su, Hisayuki Yokoyama, Shivani Srivastava, Richard Childs
Journal: Blood (2007)
Primary Care–Based Models for the Treatment of Opioid Use Disorder
Authors: P. Todd Korthuis, Dennis McCarty, Melissa Weimer, Christina Bougatsos, Ian Blazina, Bernadette Zakher, Sara Grusing, Beth Devine, Roger Chou
Journal: Annals of Internal Medicine (2016)

Greater integration of medication-assisted treatment (MAT) for opioid use disorder (OUD) in U.S. primary care settings would expand access to treatment for this condition. Models for integrating MAT into primary care vary in structure. This article summarizes findings of a technical report for the Agency for Healthcare Research and Quality describing MAT models of care for OUD, based on a literature review and interviews with key informants in the field. The report describes 12 representative models of care for integrating MAT into primary care settings that could be considered for adaptation across diverse health care settings. Common components of existing care models include pharmacotherapy with buprenorphine or naltrexone, provider and community education, coordination and integration of OUD treatment with other medical and psychological needs, and psychosocial services and interventions. Models vary in how each component is implemented. Decisions about adopting MAT models of care should be individualized to address the unique milieu of each implementation setting.
Modulating autophagy using hydroxychloroquine (HCQ) in patients with hormone-dependent PSA progression after local therapy for prostate cancer (PC).
Authors: T. McCarthy, T. M. Mayer, M. N. Stein, M. Anand, F. Collins, C. Jeyamohan, D. Metzger, D. Moore, E. White, R. S. DiPaola
Journal: Journal of Clinical Oncology (2011)

164 Background: Autophagy is conserved, genetically controlled catabolic response to starvation and stress whereby cells self- digest intracellular proteins and organelles by targeting them for degradation in lysosomes to generate energy and mitigate damage, thereby supporting cancer cell survival. We hypothesized that HCQ, by blocking autophagy, would slow PC growth. Methods: Pts had rising PSA after primary therapy for PC, no radiographic evidence of metastasis, no (neo)adjuvant ADT within 3 months of enrollment and testosterone &gt; 150 ng/dL. HCQ was dosed at 400 mg/day (cohort 1) or 600 mg/day (cohort 2). Endpoints were PSA response (defined as a change in slope of PSA rise by at least 25%, when log (PSA) is plotted vs. time) and assessment of safety and tolerability. Levels of p62 (which accumulates upon autophagy inhibition) and accumulation of autophagosomes (measured by EM) were assessed in blood mononuclear cells. Results: 38 pts (35 cohort 1; 3 cohort 2) of planned 64 pts with median age 65 (52-81), Gleason scores: 5 (5%), 6 (18%), 7 (55%), 8 (8%), 9 (13%) have been accrued. 30 pts have completed 6 cycles of therapy and 2 pts have completed 4 cycles of HCQ. 14/32 (44%) pts included in the analysis had a decrease in doubling time after treatment. 2 (6%) had declining PSA. Treatment was well tolerated, with grade 1 rash (10%), grade 1 nausea (10%) and grade 1 diarrhea (20%) being the predominant side effects noted. 3 pts had grade 2 toxicities (rash and diarrhea). There were no grade 3/4 toxicities. EM and p62 was assessed in 12 and 20 pts, respectively, and showed evidence of mitochondrial dysfunction and p62 accumulation. Conclusions: HCQ 400 mg/day appears to have some activity in PSA progression after localized therapy with minimal toxicity. Evaluation with higher doses of HCQ is ongoing. Assessing markers of autophagy including EM and p62 are feasible in pts and will require further validation in larger trials. No significant financial relationships to disclose.
Safety and efficacy of maintenance therapy (MT) with a nonspecific cytochrome-P 17 inhibitor (CYP17i) after response/stabilization to docetaxel in metastatic castratation-resistant prostate cancer (mCRPC) patients.
Authors: Ignacio Gil-Bazo, Ainhoa Castillo, Maria E. Zudaire, Estefania Arevalo, Omar Esteban Carranza, Juan Pablo Fusco, Eduardo Castanon, Jose Luis Perez-Gracia, José María López-Picazo, Alfonso Gurpide, Jesus Garcia-Foncillas
Journal: Journal of Clinical Oncology (2012)

145 Background: ACRPC causes &gt;30,000 deaths/year in the USA. The front-line treatment consists of docetaxel-based chemotherapy (D). 50% of patients (pts) show at least a 50% PSA decline during D and &gt;15% show a partial response (R) in measurable disease. However, most of these pts present progression (P) after a median of 6-8 months (m). mCRPC remains driven by ligand-dependent androgen (A) receptor signaling. Ketoconazole (K) is a nonspecific cytochrome-P 17 inhibitor (CYP17i) able to block adrenal A synthesis. Low-dose K (LDK), (200 mg, t.d.s) has shown interesting activity in mCRPC after P to androgen deprivation therapy (ADT). The FDA recently granted approval to Abiraterone acetate, a selective CYP17i showing a survival benefit after P to D. The role of a CYP17i in the maintenance setting after response/stabilization to D has never been studied. Methods: 38 mCRPC pts starting D after P to ADT maintained LHRHa and additionally received a median of 7 cycles (3-12) of front-line three-weekly D (75 mg/m2) plus daily prednisone (10 mg). 20/38 pts showing no progression to D were enrolled. One month after the last D cycle 10 pts were assigned to MT with LDK plus prednisone (10 mg daily) and continued to receive LHRHa while the 10 pts in the control arm continued on LHRHa alone. Progression-free survival (PFS) was the primary endpoint of the study. Results: After a median follow-up of 27 m, all pts in the control arm progressed after D treatment while 8/10 pts progressed to MT. PFS from D initiation was 11.4 m for MT and 8.9 m for control arm (p=0.025). Toxicity profiles showed no significant differences between both arms. No pts discontinued LDK for toxicity reasons. Conclusions: To our knowledge, this is the first study testing a CYP17i for MT after response/stabilization to D in mCRPC. Although this is a small cohort of pts and a longer follow-up is needed, these preliminary data show a significant benefit in PFS of more than 2 months with LDK MT compared to no MT after D with a favorable toxicity profile. Thus, a further analysis in a larger series and the potential impact of this PFS benefit on the overall survival is warranted.