tbuckley/cabot-search huggingface dataset:
Phase II study of weekly docetaxel and gemcitabine in relapsed patients (pts) with advanced, platinum-exposed non-small cell lung cancer (NSCLC)
Authors: C. J. Langer, C. Huang, K. Ruth, D. Shafer, H. Borghaei, M. Millenson, D. Mintzer, A. Staddon, J. Seldomridge, H. Tuttle, J. Treat
Journal: Journal of Clinical Oncology (2007)

18039 Background: Docetaxel (D) has, clear-cut therapeutic superiority compared to best supportive care, or ifosfamide/vinorelbine in relapsed NSCLC and, as a result, is the standard of comparison in the second line setting. In the pre-pemetrexed era, gemcitabine (G) in phase II studies also demonstrated activity in the salvage setting with favorable survival rates. We therefore mounted a phase II trial pairing these two agents in pts with progressive disease (PD) after prior platinum-based therapy. Methods: Pts with advanced NSCLC and ECOG PS 0–1 progressing either during or after prior platin-based therapy received D 40 mg/m 2 days 1 and 8, in combination with G 800 mg/m 2 days 1 and 8 every 3 wks. In the absence of dose limiting myelosuppression or other gr=3 toxicities, the dose of G was escalated on an intra-patient basis to 1 g/m 2 days 1 and 8. Pts continued treatment until disease progression or unacceptable toxicity. Results: 35 pts were enrolled: 20 pts (57%) were male; 69% were ECOG PS 1; 57% had received prior XRT. Median age was 61 (range 30–79); median time from initial diagnosis to enrollment was 12.4 months. 170 cycles total were administered (median 4, range 1–16). Overall response rate was 23% (95% CI 12–39%). Median event free survival (EFS) was 5.7 months; median overall survival 12.5 mos; with 1 year survival rate of 51%, and 2 year survival rate 20%. Those enrolled within 12 months of initial diagnosis had poorer EFS compared to those beyond 12 months (log rank p=0.04). There were no treatment-related deaths. Typical grade = 3 toxicities included neutropenia (43%), neutropenic fever (9%) diarrhea (6%), pneumonitis (9%), LFT elevations (9%) and dermatitis (9%), including nail changes. Conclusions: Combination docetaxel and gemcitabine administered days 1 and 8 every 3 weeks in good performance NSCLC pts with PD after/during platinum-based therapy appears encouraging, and presents a viable option in this population. Proof of benefit vs. docetaxel alone requires phase III testing. No significant financial relationships to disclose.
Merkel Cell Carcinoma: A Review of Current Advances
Authors: Frank Qian Zhan, Vathani Sharon Packianathan, Nathalie Charlotte Zeitouni
Journal: Journal of the National Comprehensive Cancer Network (2009)

Merkel cell carcinoma (MCC) is a rare but aggressive cutaneous malignancy of neuroendocrine origin. Its incidence has tripled over the past 15 years. This article reviews the recent advancement in diagnosis, discoveries in pathogenesis, and updates in management. The acronym, AEIOU, has been proposed to aid in clinical identification. In addition to cytokeratin 20, newer immunohistochemical stains (in particular thyroid transcription factor-1 and neurofilament protein) have proven to be essential in pathologic diagnosis. Although immune suppression and ultraviolet radiation have long been associated with the MCC oncogenesis, recent studies also show involvement of a new polyomavirus and bcl-2. Several tumor classifications have been published in the literature, with the 4-tiered system from Memorial Sloan-Kettering Cancer Center the most widely used. A similar classification with additional distinctions among nodal disease is being constructed. A multidisciplinary treatment algorithm is recommended for MCC. Surgical excision with adjuvant radiotherapy (RT) is indicated for localized tumors. RT is favored over complete lymph node dissection and chemotherapy for regional lymph node involvement. For distant metastasis, management should be individualized with a combination of palliative surgery, RT, and chemotherapy.
Phase II study of dasatinib in non-small cell lung cancer (NSCLC)
Authors: F. M. Johnson, X. Tang, H. Tran, B. Saigal, J. Erasmus, J. Kurie, L. Hwang, Y. Oh, S. Lippman, D. J. Stewart
Journal: Journal of Clinical Oncology (2009)

e19015 Background: Lung cancer is the leading cause of cancer-related deaths. Better systemic therapies are needed. One potential therapeutic target is c-Src which is expressed and activated in NSCLC patient tumors where it can mediate invasion, angiogenesis, and proliferation. Additionally, epidermal growth factor receptor (EGFR) and c-Src cooperate to promote NSCLC survival. We are conducting a phase II study of dasatinib, a tyrosine kinase inhibitor of c-Src, Abl, c-Kit, PDGFR, Btk, and EphA2. The primary objective is to determine the rate of progression free survival at 12 weeks in patients with metastatic NSCLC treated with dasatinib as front line therapy. Methods: Patients with metastatic NSCLC were treated with dasatinib (100 mg BID), with PET/CT scans every 6 weeks. KRAS and EGFR mutations, EGFR copy number, and pSrc expression were measured in pre-treatment biopsies. Blood was collected pretreatment and on day 21 to measure drug exposure (PK), pharmacodynamics (PD), and serum cytokine levels. Results: Twenty five patients have enrolled on study. Of the 16 patients evaluable for response: 1 had a partial response (PR) with no evidence of recurrence for at least 18 months (male smoker with adenocarcinoma and KRAS mutation); 6 patients had stable disease (SD) which includes 3 patients with prolonged stable disease for 4, 6, and 18 months; 9 had progressive disease (PD). Only 4 patients had a significant change in SUV (&gt;25%): decreased in 2 with PR and SD and increased in 2 with PD and SD. There is currently no clear association between EGFR and KRAS mutational analysis and response, although the sample number is small. Only 2 patients have activating EGFR mutations: one with SD and one with PD. PK, PD, and cytokine data will be presented. The most common grade 3/4 toxicity is dyspnea/pleural effusion that has led to a reduced dasatinib starting dose in subsequent patients. Conclusions: Dasatinib as a single agent has activity in a subset of patients with NSCLC. Planned correlative studies may lead to the discovery of biomarkers that predict response. Toxicities observed were consistent with prior dasatinib phase I studies in solid tumor patients. Supported by NCI/CTEP (NIH contract N01-CM-62202), The Commonwealth Foundation for Cancer Research and Bristol-Myers Squibb. [Table: see text]
Update: Interim Guidance for Prevention of Sexual Transmission of Zika Virus — United States, 2016
Authors: Alexandra M. Oster, Kate Russell, Jo Ellen Stryker, Allison Friedman, Rachel E. Kachur, Emily E. Petersen, Denise J. Jamieson, Amanda C. Cohn, John T. Brooks
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

CDC issued interim guidance for the prevention of sexual transmission of Zika virus on February 5, 2016. The following recommendations apply to men who have traveled to or reside in areas with active Zika virus transmission and their female or male sex partners. These recommendations replace the previously issued recommendations and are updated to include time intervals after travel to areas with active Zika virus transmission or after Zika virus infection for taking precautions to reduce the risk for sexual transmission. This guidance defines potential sexual exposure to Zika virus as any person who has had sex (i.e., vaginal intercourse, anal intercourse, or fellatio) without a condom with a man who has traveled to or resides in an area with active Zika virus transmission. This guidance will be updated as more information becomes available.
Quantitative assessment of cardiorespiratory fitness, skeletal muscle function, and body composition in adults with primary malignant glioma
Authors: L. Jones, A. Friedman, M. West, S. Mabe, J. Fraser, W. Kraus, H. Friedman, N. Major, D. Reardon
Journal: Journal of Clinical Oncology (2009)

e13002 Background: The neuropsychological impact of malignant glioma is well documented; the physiological and functional effects are not known. We conducted a pilot study to quantitatively assess cardiorespiratiory fitness, skeletal muscle function, and body composition of patients with primary malignant glioma. Methods: Using a cross-sectional design, patients with clinically stable postsurgical (10 ± 7 days post surgery) high-grade glioma (HGG; n=25) and low-grade glioma (LGG) were studied. Participants performed a cardiopulmonary exercise test (CPET) with expired gas analysis to assess peak exercise capacity (VO 2peak ) and other parameters of cardiovascular function. Other physiological outcomes included skeletal muscle cross-sectional area (CSA; magnetic resonance imaging), isokinetic muscle strength (isokinetic dynamometer), and body composition (air displacement plethysmography). QOL was assessed by the Functional Assessment of Cancer Therapy-Brain scale (FACT-BR). Results: CPET was a feasible and safe procedure for malignant glioma patients with no serious adverse events. Peak VO 2 indexed to total body weight and lean body mass for both groups was 13.0 mL.min -1 and 19 mL.min -1 ; the equivalent to 59% and 38% below age and sex-predicted normative values, respectively. Skeletal muscle isokinetic strength was significantly lower in HGG relative to LGG patients (83 vs. 125 Nm, p=.025) and predicted peak VO 2 (r = 0.44, p&lt;0.05). In patients with HGG, only self-reported exercise behavior was correlated with QOL (r = 0.42; p=.046) while sex (male) (r = 0.44; p=.037), lean mass (r = -0.41; p=.049), and VO 2peak (r = -0.40; p=.052) were associated with fatigue. Conclusions: CPET is a safe and feasible tool to evaluate physical functioning in select patients with malignant glioma. Postsurgical glioma patients have markedly reduced exercise capacity, isokinetic strength and CSA. Muscle strength is an important contributor to poor VO 2peak in this population. Prospective studies are now required to determine whether such abnormalities influence prognosis as well as test the effect of appropriately selected interventions to prevent and/or mitigate dysfunction. No significant financial relationships to disclose.
Rat Alpha1-Fetoprotein: Appearance After GalactosamineInduced Liver Injury2
Authors: S. Sell, D. Reynolds, W. Reutter
Journal: JNCI Journal of the National Cancer Institute (1974)

Journal Article Rat Alpha1-Fetoprotein: Appearance After GalactosamineInduced Liver Injury Get access S. Sell, S. Sell 3Department of Pathology, University of California, San Diego, Medical School, La Jolla, Calif. 92037. Search for other works by this author on: Oxford Academic PubMed Google Scholar D. Reynolds, D. Reynolds 4Department of Biochemistry, University of Wisconsin, Madison, Wis. 53706. Search for other works by this author on: Oxford Academic PubMed Google Scholar W. Reutter W. Reutter 5Institute of Biochemistry, University of Freiburg, Freiburg, Germany. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 53, Issue 1, July 1974, Pages 289–291, https://doi.org/10.1093/jnci/53.1.289 Published: 01 July 1974 Article history Received: 05 April 1974 Accepted: 12 April 1974 Published: 01 July 1974
Phylogenetic relationships and biogeography of xantusiid lizards, inferred from mitochondrial DNA sequences.
Authors: S B Hedges, R L Bezy, L R Maxson
Journal: Molecular Biology and Evolution (1991)

Portions of two mitochondrial genes (12S ribosomal RNA and cytochrome b) were sequenced in seven species to examine phylogenetic relationships within the lizard family Xantusiidae. Phylogenies derived from these sequences (709 total bp) are concordant and indicate that the Cuban species Cricosaura typica is the sister group to all other xantusiids. The Middle American genus Lepidophyma is the closest relative of Xantusia, and X. riversiana (California Islands) the closest relative of X. vigilis (mainland). These findings are not in agreement either with the results of a recent morphological analysis that united Cricosaura and Lepidophyma as closest relatives or with past studies that have recognized X. riversiana as a separate genus. Levels of sequence divergence, as well as the age and affinities of some mainland fossil taxa, suggest that the origin of Cricosaura was associated with the tectonic evolution of the Greater Antilles in the late Cretaceous. These results further demonstrate that significant resolution of phylogenies can be obtained with relatively short DNA sequences and that these mitochondrial genes are concordant in their estimation of phylogeny.
Use of Nomograms for Early Detection in Prostate Cancer
Authors: Devon C. Snow, Eric A. Klein
Journal: Journal of the National Comprehensive Cancer Network (2010)

Since the first introduction of prostate-specific antigen (PSA) as a screening tool in the 1980s, the accurate diagnoses of clinically significant prostate cancer remains a challenge. Analysis of a correlation between PSA levels and prostate biopsies of men with PSA 3 ng/mL or less in the placebo group of the Prostate Cancer Prevention Trial suggested that no "normal" PSA level exists. With the acknowledgement that PSA level is considered a continuum rather than a dichotomous marker, accurately diagnosing clinically significant prostate cancer is even more challenging. Nomograms are increasingly being used as tools in the clinical setting to address this challenge. Through incorporating multiple clinical factors, such as PSA, digital rectal examination, age, race, prostate volume, family history, and previous negative biopsy, risk calculators can improve sensitivity of diagnosis over using a PSA cutoff alone. This article discusses the rational for the use of nomograms and the advantages and limitations for the most commonly used nomograms.
Induction of Tumors in Marmoset Monkeys by Simian Sarcoma Virus, Type 1 (<italic>Lagothrix</italic>): A Preliminary Report<xref ref-type="fn" rid="FN1">2</xref>
Authors: L G Wolfe, F Deinhardt, G H Theilen, H Rabin, T Kawakami, L K Bustad
Journal: JNCI Journal of the National Cancer Institute (1971)

Marmoset monkeys developed fibromas or well-differentiated fibrosarcomas 7–30 days after inoculation with simian sarcoma virus type 1 (Lagothrix), C-type virus particles were demonstrated in the tumors and cell cultures derived from the tumors. The morphologic appearance of the tumors, the clinical course, and the viral expression in this system were compared to the tumors induced in marmosets by feline sarcoma and Rous sarcoma viruses.
Using administrative data to describe adherence to colon cancer follow-up testing in Manitoba, Canada.
Authors: J. J. Sisler, B. Seo, A. Katz, E. Shu
Journal: Journal of Clinical Oncology (2010)

6079 Background: Relapse after treatment of early-stage colon cancer is common, but meta-analyses have demonstrated a 7%- 10% reduction in absolute mortality with follow-up testing using a combination of CEA testing, liver imaging and colonoscopy. This study uses administrative data to describe adherence to such testing at a population level, and examines patient, provider, disease and treatment factors that are associated with better adherence. Methods: Data was obtained by linking the Manitoba Population Health Research Data Repository with the Manitoba Cancer Registry and Laboratory Claims data. An expert committee recommended standards of test performance based on the 2005 ASCO guidelines. A cohort of 171 patients was identified, diagnosed with stage II or III colon cancer in 2004 who were alive 42 months after diagnosis. Data include physician contacts and performance of liver imaging, colonoscopy, and CEA testing over a 3-year period from 6 to 42 months after diagnosis. Multivariate logistic regression was used to assess the performance of each test at the recommended standard against variables including visits by physician specialty, treatment, stage, and patient characteristics. Data for CEA and liver imaging was available only for urban patients. Results: 84% of the cohort received at least one follow-up colonoscopy, with stage II patients and those with at least one visit yearly with a surgeon more likely to be adherent. 54% had at least one liver imaging test per year, with adherence predicted by receiving chemotherapy and at least one visit yearly with a medical oncologist. Only 19% received 3 or more CEA tests per year, with adherence predicted by higher stage and at least one visit yearly with a medical oncologist. Twelve per cent met the standards for all three tests over the 3 years. Conclusions: Adherence to CEA testing and liver imaging falls well below guidelines even in this “best” patient group. Colonoscopy is better provided. Regular contact with a medical oncologist, stage and provision of chemotherapy are important drivers of complete follow-up, but adherence is low for all groups. This quality of care gap needs to be addressed with interventions aimed at patients, physicians and at the system level. No significant financial relationships to disclose.
Internal transcribed spacer guided multiplex PCR for species identification of Convolvulus prostratus and Evolvulus alsinoides
Authors: Sonal Sharma, Neeta Shrivastava
Journal: Acta Pharmaceutica Sinica B (2016)

Shankhpushpi is a reputed drug from an Indian system of medicine for treating mental disorders and enhancing memory. Two herbs, namely Convolvulus prostratus Forssk. and Evolvulus alsinoides (L.) L., are commonly known as Shankhpushpi. Ambiguous vernacular identity can affect the scientific validity of the Shankpushpi-based herbal drug therapy. In the present investigation, a novel and sensitive multiplex PCR method based on polymorphism in the internal transcribed spacer (ITS) region was developed to establish the molecular identity of C. prostratus and E. alsinoides. DNA was isolated and the ITS region was amplified, sequenced and assembled. Sequences were aligned to identify variable nucleotides in order to develop plant-specific primers. Primers were validated in singleplex reactions and eventually a multiplex assay was developed. This assay was tested for sensitivity and validated by amplifying DNA isolated from the simulated blended powdered plant material. Primers developed for C. prostratus resulted into a 200 bp amplicon and 596 bp for E. alsinoides. The assay was found to be sensitive enough for amplification of low quantities of DNA. The method can detect 10% of the mixing of plants with each other in blended material. This PCR assay can be used for rapid botanical identification of Shankhpushpi plant materials and will improve evidence-based herbal drug therapy.
Neoplastic gastrointestinal pathology: an illustrated guide
Authors: Fiona Campbell
Journal: Gut (2016)

Laura W Lamps, Andrew M Bellizzi, Wendy L Frankel, Scott R Owens & Rhonda K Yantiss. DemosMEDICAL, New York, 2016; ISBN:978-1-936287-72-7

The title of this book would not have attracted my attention prior to being asked to review it. Neoplasia is covered in detail in existing GI pathology textbooks and there are also atlases of GI pathology. A quick glance at the contents, however, and I think the book should have been entitled ‘A Practical Guide (or Approach) to Neoplastic Gastrointestinal Pathology’.

The introductory chapter covers terminology, grading, staging, reporting and screening, as well as a general approach to …
NICE guidance on menopause: cognitive behavioural therapy is an effective non-hormonal intervention for managing vasomotor symptoms
Authors: Myra S Hunter, Amanda Griffiths, Eleanor Mann, Rona Moss-Morris, Melanie Smith, Pauline Slade
Journal: BMJ (2015)

The full document of the first National Institute for Health and Care Excellence (NICE) guideline on diagnosis and management of menopause1 recommends (page 18) that GPs should: "Give information to menopausal women and their family members or carers (as appropriate) about the following types of treatment for menopausal symptoms:
Current Concepts in Penile Cancer
Authors: Philippe E. Spiess, Simon Horenblas, Lance C. Pagliaro, Matthew C. Biagioli, Juanita Crook, Peter E. Clark, Richard E. Greenberg, Cesar E. Ercole
Journal: Journal of the National Comprehensive Cancer Network (2013)

This review highlights the significant advances made in the diagnosis and management of penile cancer. This often-aggressive tumor phenotype has been characterized by its poor prognosis, mostly attributable to its late presentation and heterogeneity of surgical care because of the paucity of cases treated at most centers. Recent advances in understanding of the risk factors predisposing to penile cancer, including its association with the human papilloma virus (HPV), have brought forth the socioepidemiologic concept of HPV vaccination in certain high-risk populations and countries, which remains highly debated. The management of penile cancer has evolved in recent years with the adoption of penile-sparing and minimally invasive surgical approaches to the inguinal lymph nodes, which are a frequent site of regional spread for this malignancy. Lastly, this review highlights the importance of adopting a multimodal approach consisting of neoadjuvant systemic chemotherapy followed by consolidative surgical resection in patients presenting with bulky/locally advanced nodal metastases from penile cancer.
PTU-048 Correlating urinary metabolic profiles with serological and genetic determinants of inflammatory bowel disease
Authors: H R T Williams, I J Cox, D G Walker, H Sato, S D Taylor-Robinson, S E Marshall, T R Orchard
Journal: Gut (2010)

<h3>Introduction</h3> Subgroups of inflammatory bowel disease (IBD) patients have specific serological and genetic associations, reflecting abnormal immunogenetic responses to enteric microbes. We have recently shown significant differences between the urinary metabolic profiles of Crohn9s disease (CD) patients, ulcerative colitis (UC) patients and healthy control individuals.1 The differentiating metabolites included several strongly influenced by gut microbial metabolism. <h3>Methods</h3> It was hypothesised that the urinary metabolic profiles of CD patients would differ depending on possession of 1) anti-Saccharomyces cerevisiae antibodies (ASCA) and antibodies to an <i>E coli</i> outer membrane porin (anti-Omp C), and 2) CD-associated CARD15/NOD2 polymorphisms. It was hypothesised that profiles of UC patients would differ depending on their possession of perinuclear anti-neutrophil cytoplasmic antibodies (pANCA). Urinary metabolic profiles were acquired from 74 CD and 50 UC patients, with nuclear magnetic resonance spectroscopy. Sera were assayed for ASCA IgA and IgG, anti-Omp C (CD) and pANCA (UC) status; CD patients were genotyped for CD-associated CARD15/NOD2 polymorphisms. Multivariate analysis was carried out to investigate differences between the CD cohort depending on ASCA, anti-Omp C and CARD15/NOD2 status, and the UC cohort depending on pANCA status. This involved partial least squares discriminant analysis with orthogonal signal correction (OSC-PLS-DA), with leave-one-out cross-validation of the multivariate models created. <h3>Results</h3> OSC-PLS-DA modelling discriminated the profiles of CD patients possessing ASCA (58% of the cohort) from those who did not, with a statistically significant Q<sup>2</sup> value of 0.31 (sensitivity 88%, specificity 60%). The major contributory metabolites to this model included the gut microbe-related metabolites hippurate, lower in the group seropositive for ASCA, and trimethylamine-N-oxide (TMAO), higher in this group. No significant distinctions were found between CD urinary profiles analysed according to anti-Omp C or CARD15/NOD2 status, nor UC profiles when stratified by pANCA status. <h3>Conclusion</h3> The urinary metabolic profiles of CD patients with ASCA differ significantly from those without. The involvement of hippurate and TMAO in this multivariate model suggests that gut microbial metabolism differs in CD patients possessing ASCA.