tbuckley/cabot-search huggingface dataset:
Severe chemotherapy induced diarrhea (CID) in patients with colorectal cancer: A cost of illness analysis
Authors: G. Dranitsaris, J. Maroun, A. Shah
Journal: Journal of Clinical Oncology (2004)

6087 Background: Considerable cancer supportive care research has been devoted to febrile neutropenia, emesis and anemia. In contrast, diarrhea as a side effect of chemotherapy has received less attention. However, CID is common with many types of chemotherapy and can have a major impact on maintaining dose intensity, treatment effectiveness and on overall health care resources. In this study, a cost of illness analysis was conducted to estimate the overall economic impact of grade III/IV diarrhea in patients with colorectal cancer receiving chemotherapy. Methods: This was a retrospective cohort study consisting of patients with colorectal cancer that had received chemotherapy and had developed grade III or IV diarrhea. Data collection included patient demographics, disease related information and healthcare resource utilization to manage the grade III/IV CID event. Multivariable logistic regression analysis was then used to identify factors associated with hospitalization for uncontrolled CID. Results: Patients (n=96) had a mean age of 60.3 years and 49% of the sample was receiving adjuvant chemotherapy with a curative intent. The severe CID developed after the first cycle of chemotherapy in 54.2% of patients and was responsible for a median dose reduction and delay of 20% and 7 days respectively. Overall, 30 of 96 patients (31%) with severe CID required a hospital admission for supportive care with an 8-day median length of stay (range = 2 to 28 days). There were 2 deaths with 1 possibly being related to the diarrhea. When the economic impact of the grade III/IV CID was quantified, the mean cost was $2,559 per patient (95%CI: $1,665 to $3,453). The logistic regression analysis identified grade IV diarrhea (OR=9.9; P < 0.001) and severe CID developing after the first chemotherapy cycle (OR=3.6; P = 0.026) as significant predictors of patient hospitalization. Conclusions: Grade III/IV diarrhea is a debilitating and costly complication of chemotherapy in colorectal cancer. Effective interventions that prevent the development of severe CID need to be identified to save health care costs and reduce patient morbidity. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis Novartis Canada
Antcin G4, an ubiquinone derivative, displays anticancer activity through inhibition on protein synthesis: The roles of p70S6K and eIF4E pathways
Authors: Ssu-Chia Lin, Sheng-Yung Liu, Mao-Tien Kuo, Wu-Che Wen, Po-Cheng Chiang, Jih-Hwa Guh
Journal: Clinical Cancer Research (2007)

B22  Hepatocellular carcinoma (HCC) is a leading cause of cancer death worldwide. Currently, there is little effective clinical treatment for this highly malignant tumor and, therefore, numerous strategic approaches have been developed to seek effective chemotherapeutic agents. Antcin G4, an ubiquinone derivative, is isolated from the solid-state fermented mycelium of Antrodia camphorate. The sulforhodamine B assays showed that antcin G4 induced an inhibitory effect on HCC proliferation with IC50 values of 0.13 and 1.5 μM in HepG2 and Hep3B cells. Because of the higher potency in HepG2 cells, the anticancer mechanism of antcin G4 was delineated accordingly. The release of HepG2 cells from thymidine block caused a definite cell-cycle progression of zero time at G1-phase, 3 hours at S-phase and 6 hours at G2/M-phase. The cell-cycle progression was arrested by antcin G4 predominantly at G1- and S-phase. The Western blot analysis demonstrated that the expression of several cell-cycle regulators, including cyclin-D1, cyclin-E, Cdk4 and Cdk2, was down-regulated by antcin G4. Notably, the down-regulation of Cdk4 occurred at an early exposure of two-hour to antcin G4. Since the eukaryotic translation initiation factor 4E (eIF4E) and p70S6K play an important role in the control of translation, these regulatory systems were detected. As a result, antcin G4 inhibited both p70S6K phosphorylation of at Thr421 and Ser424 and 4E-BP-1 phosphorylation. To correlate with the block of 4E-BP-1 phosphorylation, the eIF4E was de-phosphorylated by antcin G4, indicating that antcin G4 may inhibit the translation machinery. Furthermore, antcin G4 inhibited the incorporation of [3H]leucine in a time-dependent fashion, confirming the inhibition of translational function. The upstream effectors responsible for translation were also determined. The data showed that an early exposure of cells to antcin G4 inhibited the activation of phsophatidylinositol 3-kinase (PI 3-K) and p38 mitogen-activated protein kinase (MAPK), but not p42/p44 MAPKs. Taken together, the data suggest that antcin G4 inhibits the activation of PI 3-K and p38 MAPK, leading to the de-phosphorylation and inhibition of p70S6K and eIF4E activity. Finally, the expressions of cell-cycle regulators were inhibited and the cell-cycle progression was arrested at G1 and S-phase, explaining antcin G4-induced anti-proliferative effect in HepG2 cells.
Phase I study to evaluate the safety and tolerability of MEDI4736, an anti-programmed cell death ligand-1 (PD-L1) antibody, in Japanese patients with advanced solid tumors.
Authors: Haruo Iguchi, Naoyuki Nogami, Toshiyuki Kozuki, Toshihiko Matsumoto, Kenji Tamura, Noboru Yamamoto, Akihiko Shimomura, Yuji Hoshino, Yoshiko Michibata, Masahiro Nii, Yutaka Fujiwara
Journal: Journal of Clinical Oncology (2015)

3039 Background: Immune-suppressing molecules can be exploited by tumor cells to suppress immune responses to cancer. Programmed cell death-1 (PD-1) is an inhibitory regulator of T-cell activation. The ligand to PD-1, PD-L1, is upregulated in several tumor types. MEDI4736 is a human IgG1 mAb that blocks PD-L1 binding to PD-1 and CD80 with high affinity and selectivity. Methods: This Phase 1, multicenter, open-label study (NCT01938612) is evaluating the safety, PK, and clinical activity of MEDI4736 in Japanese patients (pts) with advanced solid tumors. Pts ( ≥ 20 years) with ECOG performance status 0–1 who are refractory or intolerant to standard treatment or for whom no standard treatment exists are eligible. MEDI4736 was given IV every 2, 3, or 4 wks (q2/3/4w) using a 3+3 dose escalation, followed by a dose-expansion phase that includes further pts at or below the maximum tolerated dose. Treatment continues for up to 12 months; retreatment is possible upon progression after 12 months. Disease response was assessed by RECIST v1.1. Results: As of 27 November 2014, 22 pts were enrolled across 5 dose levels. Drug-related adverse events (AEs) ≥ Grade (G) 2 were pneumonitis (G2; 3 mg/kg q2w), oral stomatitis (G2; 3 mg/kg q2w), constipation (G2; 3 mg/kg q2w), hypothyroidism (G2; 15 mg/kg q3w), eruption (G2, 20 mg/kg q4w), skin atheroma (G2, 1 mg/kg q2w), mucositis (G2; 3 mg/kg q2w), and serum-free triiodothyronine decreased (FT3; G3; 10 mg/kg q2w); all n = 1. There were no G4 drug-related AEs. G2 pneumonitis and G3 low serum FT3 were considered serious drug-related AEs. 1 pt discontinued due to an AE; G1 pneumonitis. No drug-related deaths or dose-limiting toxicities (DLTs) were reported. Of 19 evaluable pts with ≥ 1 post-baseline CT assessment, 1 pt (10 mg/kg q2w) had a partial response, and 6 pts had stable disease (n = 2 at 1 mg/kg q2w, and n = 1 each at 3 mg/kg q2w, 10 mg/kg q2w, 15 mg/kg q3w, and 20 mg/kg q4w). Conclusions: Initial results indicate no DLTs, 7 G2- and 1 G3-related AEs, and clinical activity for MEDI4736 in Japanese pts with advanced solid tumors. Based on these data, an expansion phase, including biliary tract cancer, SCCHN, and esophageal tumors, is underway. Clinical trial information: NCT01938612.
Types of Tumor Induced by Ultraviolet Radiation and Factors Influencing Their Relative Incidence
Authors: Hugh G. Grady, Harold F. Blum, John S. Kirby-Smith
Journal: JNCI Journal of the National Cancer Institute (1943)

Journal Article Types of Tumor Induced by Ultraviolet Radiation and Factors Influencing Their Relative Incidence Get access Hugh G. Grady, Hugh G. Grady formerly acting assistant surgeon Search for other works by this author on: Oxford Academic PubMed Google Scholar Harold F. Blum, Harold F. Blum senior pharmacologist Search for other works by this author on: Oxford Academic PubMed Google Scholar John S. Kirby-Smith John S. Kirby-Smith assistant physicist National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 3, Issue 4, February 1943, Pages 371–378, https://doi.org/10.1093/jnci/3.4.371 Published: 01 February 1943
Intense exercise for survival among men with metastatic castrate-resistant prostate cancer (INTERVAL – MCRPC): A Movember funded multicenter, randomized, controlled phase III study.
Authors: Fred Saad, Stacey A. Kenfield, June M. Chan, Nicolas H. Hart, Kerry S. Courneya, James Catto, Stephen P. Finn, Rosemary Greenwood, Daniel C Hughes, Lorelei A. Mucci, Stephen R Plymate, Michael N. Pollak, Stephan F.E. Praet, Aaron P. Russell, Emer M. Guinan, Erin Van Blarigan, Orla Casey, Mark Buzza, Charles J. Ryan, Robert Usher Newton
Journal: Journal of Clinical Oncology (2016)

TPS5092 Background: Provocative evidence supports the beneficial role of physical activity on prostate cancer survivorship. Evaluating exercise as a low-toxicity adjuvant intervention that can be combined with standard therapy to improve outcomes in men with prostate cancer could reduce the clinical and public health burden of the disease. Exercise may affect prostate cancer survival via inflammation, hormonal, and energy metabolism pathways. Methods: Our goal is to compare overall survival (OS) among men with MCRPC randomly assigned to psychosocial support +/- high intensity aerobic and resistance training for 24 months. Secondary outcomes include: time to disease progression, occurrence of a skeletal-related event, or progression of pain; and degree of pain, opiate use, and physical and emotional quality of life. We will assess if inflammation, dysregulation of insulin and energy metabolism, and androgen biomarkers are associated with OS, and if they mediate the primary association between exercise and OS. The study will establish a biobank for future biomarker discovery or validation. This multi-site global trial will include MCRPC patients who are treatment naive or on abiraterone and/or enzalutamide without evidence of progression at enrolment. Patients will be randomized (1:1) to psychosocial support +/- high intensity aerobic and resistance training. The first 12 months of training will include a structured period of tapered supervised exercise with increasing self-managed exercise and behavioral support with text messages, to support self-management for an additional 12 months. Exercise prescriptions will be tailored to participant's fitness and cancer/treatment morbidities. Assuming a median OS of 33.5 months in the controls, the sample size to detect a hazard ratio of 0.78 with 80% power at significance level of 0.05 is 824; assuming missing data on OS for 5%, we aim to enroll 866 men. Conclusion: This is the first prospective randomized trial to examine exercise and survival in men with prostate cancer; and is designed to elucidate the mechanisms by which exercise delays cancer progression.
Long-Term, Supplemental, One-Carbon Metabolism–Related Vitamin B Use in Relation to Lung Cancer Risk in the Vitamins and Lifestyle (VITAL) Cohort
Authors: Theodore M. Brasky, Emily White, Chi-Ling Chen
Journal: Journal of Clinical Oncology (2017)

Purpose Inconsistent findings have been reported of a link between the use of one-carbon metabolism-related B vitamins and lung cancer risk. Because of the high prevalence of supplemental vitamin B use, any possible increased association warrants further investigation. We examined the association between long-term use of supplemental B vitamins on the one-carbon metabolism pathway and lung cancer risk in the Vitamins and Lifestyle (VITAL) cohort, which was designed specifically to look at supplement use relative to cancer risk. Methods A total of 77,118 participants of the VITAL cohort, 50 to 76 years of age, were recruited between October 2000 and December 2002 and included in this analysis. Incident, primary, invasive lung cancers (n = 808) were ascertained by prospectively linking the participants to a population-based cancer registry. The 10-year average daily dose from individual and multivitamin supplements were the exposures of primary interest. Results Use of supplemental vitamins B6, folate, and B12 was not associated with lung cancer risk among women. In contrast, use of vitamin B6 and B12 from individual supplement sources, but not from multivitamins, was associated with a 30% to 40% increase in lung cancer risk among men. When the 10-year average supplement dose was evaluated, there was an almost two-fold increase in lung cancer risk among men in the highest categories of vitamin B6 (> 20 mg/d; hazard ratio, 1.82; 95% CI, 1.25 to 2.65) and B12 (> 55µg/d; hazard ratio, 1.98; 95% CI, 1.32 to 2.97) compared with nonusers. For vitamin B6 and B12, the risk was even higher among men who were smoking at baseline. In addition, the B6 and B12 associations were apparent in all histologic types except adenocarcinoma, which is the type less related to smoking. Conclusion This sex- and source-specific association provides further evidence that vitamin B supplements are not chemopreventive for lung cancer and may be harmful.
Bevacizumab plus paclitaxel optimization study with interventional maintenance endocrine therapy in advanced or metastatic ER-positive HER2-negative breast cancer: JBCRG-M04 (BOOSTER) trial.
Authors: Shigehira Saji, Masakazu Toi, Takashi Ishikawa, Takanori Ishida, Shoichiro Ohtani, Masahiro Kashiwaba, Yasuaki Sagara, Shigenori E. Nagai, Yoshie Hasegawa, Tomomi Fujisawa, Norikazu Masuda, Koji Matsumoto, Yutaka Yamamoto, Hiroshi Yoshibayashi, Naruto Taira, Satoshi Morita, Shinji Ohno
Journal: Journal of Clinical Oncology (2014)

TPS657 Background: In the standard management of inoperable or recurrent breast cancer (BC), active therapy is continued until disease progression (PD) or unacceptable toxicity. In patients (pts) receiving first-line bevacizumab (BV) plus paclitaxel (PTX), this strategy results in some pts discontinuing treatment because of PTX-related peripheral sensory neuropathy despite sustained tumor response. To overcome this problem, we propose a practical treatment strategy in pts with ER-positive HER2-negative BC, introducing temporary BV + endocrine maintenance therapy in pts responding to BV + PTX followed by BV + PTX reintroduction at first PD. This strategy may reduce the impact of peripheral sensory neuropathy, enable pts to maintain their quality of life (QOL) and prolong disease control. Methods: JBCRG-M04 (BOOSTER; UMIN000012179; ClinicalTrials.gov NCT01989780) is a multicenter open-label randomized phase II trial in pts with ER-positive HER2-negative inoperable or recurrent BC. After 16–24 weeks of induction therapy with BV 10 mg/kg q2w + PTX 90 mg/m2 days 1, 8 and 15 q4w, pts achieving a complete or partial response or stable disease (investigator assessed) are randomized to either A: continued BV + PTX; or B: a switch to maintenance BV + endocrine therapy, followed by BV + PTX at the time of either PD or clinical PD on maintenance therapy. Tumor tissue, DNA and sequential plasma samples are collected before and during treatment for biomarker research. The primary endpoint is time to failure of strategy (TFS), defined as the interval between randomization and either PD on study therapy, change to new agent not in study regimen, first PD not followed by BV + PTX in arm B, or death. The planned sample size of 160 pts provides 80% power to detect a 6-month increase in TFS in arm B versus arm A. Secondary endpoints include overall survival, 2-year survival rate, progression-free survival, safety and QOL. Biomarker analyses include correlations between biomarkers and response, changes in angiogenesis regulators and comparison of biomarker levels between initial and reintroduced BV + PTX. Clinical trial information: NCT01989780.
<i>D</i><sub>LCO</sub>: adjust for lung volume, standardised reporting and interpretation
Authors: Douglas C. Johnson
Journal: European Respiratory Journal (2017)

<b><i>D</i></b><sub><b>LCO</b></sub><b>reports and interpretation should be standardised and include adjusting predicted <i>D</i></b><sub><b>LCO</b></sub><b>and <i>K</i></b><sub><b>CO</b></sub><b>for lung volume</b>http://ow.ly/ywTA30cOh44
Trial of ZMapp for Ebola Virus Infection
Authors: Richard T Davey, Jacquie Nordwall, Michael A Proschan
Journal: New England Journal of Medicine (2017)

Programme on HIV/AIDS, 2014 (http://www .unaids.org/sites/ default/ files/ media _asset/ UNAIDS_Gap_report_en .pdf). 4. Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach -second edition.
Adipochemokines induced by ultraviolet irradiation contribute to impaired fat metabolism in subcutaneous fat cells
Authors: E.J. Kim, Y.K. Kim, S. Kim, J.E. Kim, Y.D. Tian, E.J. Doh, D.H. Lee, J.H. Chung
Journal: British Journal of Dermatology (2017)

Adipose tissue is now appreciated as the pivotal regulator of metabolic and endocrine functions. Subcutaneous (SC) fat, in contrast to visceral fat, may protect against metabolic syndrome and systemic inflammation. We demonstrated that chronic as well as acute ultraviolet (UV) irradiation to the skin induces loss of underlying SC fat. UV-irradiated SC fat may produce chemokines or cytokines that modulate lipid homeostasis and secretion of adipokines.To elucidate UV-induced specific adipochemokines implicated in UV-induced modulation of SC fat.Primary cultured adipocytes were treated with conditioned medium from UV- or sham-irradiated skin cells. Young and older healthy participants provided SC fat from sun-exposed and sun-protected skin. Sun-protected skin from other participants was irradiated with UV. Differentially expressed adipochemokines were screened by cytokine array, and confirmed in vitro and in vivo. The functions of select adipochemokines involved in lipid metabolism were examined via short interfering RNA-mediated knockdown of cognate receptors.Specific adipochemokines, including C-X-C motif chemokine (CXCL) family members such as CXCL5/ENA-78, and C-C motif chemokine (CCL) family members such as CCL20/MIP-3α and CCL5/RANTES, were greatly induced in SC fat by UV exposure. They could impair triglyceride synthesis via downregulation of lipogenic enzymes and sterol regulatory element-binding protein-1 through their respective cognate receptors, CXC chemokine receptor type (CXC-R)2, C-C chemokine receptor type (CCR)-6, and CCR-5. In addition, UV irradiation induced infiltration of adipose tissue macrophages responsible for the secretion of several chemokines into SC fat.These UV-induced adipochemokines may be implicated in the reduction of lipogenesis in SC fat, leading to impairment of fat homeostasis and associated comorbidities such as obesity.
Risk of atrial fibrillation in people with type 1 diabetes compared with matched controls from the general population: a prospective case-control study
Authors: Sofia Dahlqvist, Annika Rosengren, Soffia Gudbjörnsdottir, Aldina Pivodic, Hans Wedel, Mikhail Kosiborod, Ann-Marie Svensson, Marcus Lind
Journal: The Lancet Diabetes & Endocrinology (2017)
Progression-free survival as a surrogate for overall survival in advanced cancer.
Authors: Eric Gillies, Veera Holdai, David Eric Cowall
Journal: Journal of Clinical Oncology (2015)

e17765 Background: Progression-free survival (PFS) is sometimes being used instead of overall survival (OS) as a primary end-point in clinical trials of advanced cancer patients (ACP). We examine the efficacy of PFS as a surrogate for OS in ACP. Methods: The Peninsula Regional Medical Center Cancer Registry was used as a database to measure PFS and OS from 82 consecutive cancer deaths in Wicomico County, Maryland beginning January 1, 2014 for which RECIST 1.1 guidelines could be obtained. Of the total, there were 33 females and 31 lung cancer patients. Logarithm transformation of PFS and OS was done to obtain normality of residuals for valid linear regression analyses. Results: For all cancers, the median PFS was 6.2 months, and the median OS was 15.6 months. For the lung cancer subset, the median PFS was 4.1 months, and the median OS was 13.8 months. PFS predicted for OS 30.5% and 32.3% of the time, respectively. Conclusions: PFS was not a suitable surrogate for OS in this sample of cancer deaths from our institution.
Polygenic Scores for Major Depressive Disorder and Risk of Alcohol Dependence
Authors: Allan M. Andersen, Robert H. Pietrzak, Henry R. Kranzler, Li Ma, Hang Zhou, Xiaoming Liu, John Kramer, Samuel Kuperman, Howard J. Edenberg, John I. Nurnberger, John P. Rice, Jay A. Tischfield, Alison Goate, Tatiana M. Foroud, Jacquelyn L. Meyers, Bernice Porjesz, Danielle M. Dick, Victor Hesselbrock, Eric Boerwinkle, Steven M. Southwick, John H. Krystal, Myrna M. Weissman, Douglas F. Levinson, James B. Potash, Joel Gelernter, Shizhong Han
Journal: JAMA Psychiatry (2017)

Major depressive disorder (MDD) and alcohol dependence (AD) are heritable disorders with significant public health burdens, and they are frequently comorbid. Common genetic factors that influence the co-occurrence of MDD and AD have been sought in family, twin, and adoption studies, and results to date have been promising but inconclusive.
Treatment of localized gastric and gastroesophageal adenocarcinoma: the role of accurate staging and preoperative therapy
Authors: Brian Badgwell, Prajnan Das, Jaffer Ajani
Journal: Journal of Hematology & Oncology (2017)

Gastric cancer is the third most common cause of cancer death worldwide, although it is not in the top 10 causes of cancer death in Northern America. Due to clear differences in incidence, screening, risk factors, tumor biology, and treatment between gastric cancers from Eastern and Western countries, our treatment is primarily guided by trials from Western countries. Patients undergo an extensive staging evaluation including high-quality CT imaging, endoscopic ultrasound, and diagnostic laparoscopy with peritoneal washings for cytology. Patients are presented in multidisciplinary conference with input from medical, radiation, and surgical oncology, in addition to further evaluation of existing studies and biopsy results by diagnostic radiology and pathology colleagues. Due to the well-documented difficulty in tolerating postoperative therapy, patients are frequently treated with preoperative chemotherapy and chemoradiotherapy. Extended lymph node (D2) dissection is routinely performed during subtotal or total gastrectomy. Ongoing trials in Western populations comparing preoperative chemotherapy to chemoradiotherapy will help inform the decision regarding the optimal treatment for patients with resectable gastric cancer. Additional studies are needed to identify predictors of treatment response to identify the optimal preoperative or perioperative approach. As peritoneal disease is the most common site of recurrence, studies are also urgently needed for more accurate methods of detecting peritoneal disease at diagnosis, and also investigating potential treatment modalities such as hyperthermic intraperitoneal chemotherapy.