tbuckley/cabot-search huggingface dataset:
Clinicopathologic and Biological Significance of Kallikrein 6 Overexpression in Human Gastric Cancer
Authors: Hisashi Nagahara, Koshi Mimori, Tohru Utsunomiya, Graham F. Barnard, Masaichi Ohira, Kosei Hirakawa, Masaki Mori
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Human kallikrein genes (KLK) have been reported to be involved in human malignancies and several KLKs are promising biomarkers of prostate, ovarian, testicular, and breast cancers. Herein, we investigated the clinicopathologic and biological significance of KLK6 gene expression in human gastric cancer. Patients and Methods: Using real-time reverse transcription-PCR, we analyzed the KLK6 expression status with respect to various clinicopathologic variables in 66 patients with gastric cancer. In addition, we established a KLK6 stably suppressed gastric cancer cell line (MKN28) using small interfering RNA–mediated gene silencing, and investigated its effects on the cell proliferation rate, cell cycle, and invasiveness. Results: The KLK6 gene expression in cancerous tissue (0.37 ± 0.53) was significantly (P &amp;lt; 0.000001) higher than that in noncancerous tissue (0.026 ± 0.060). Elevated KLK6 expression was significantly associated with lymphatic invasion (P = 0.03). Furthermore, patients with a high KLK6 expression had a significantly poorer survival rate than those with a low KLK6 expression (P = 0.03). Therefore, we showed that KLK6 gene silencing with KLK6 small interfering RNA effectively suppressed the cell proliferation rate (P = 0.002), cell population in the S phase (P &amp;lt; 0.01), and invasiveness (P &amp;lt; 0.01) in comparison to mock-transfected cells. Conclusions: The KLK6 gene is markedly overexpressed in gastric cancer tissue and its expression status may be a powerful prognostic indicator for patients with gastric cancer. Our findings also suggest that KLK6 may possibly be a novel target for gastric cancer therapy by gene-silencing procedures.
THE TISSUE SPECIFICITY OF BRAIN AND MEDULLATED NERVES AS SHOWN BY PASSIVE ANAPHYLAXIS IN GUINEA PIGS
Authors: G. Howard Bailey, Raymond E. Gardner
Journal: The Journal of Experimental Medicine (1940)

Prolonged immunization of rabbits with a sedimented, heat-killed vaccine of Pasteurella boviseptica grown in an infusion broth prepared from rat brain resulted in the production of antisera containing antibodies for the broth as well as for the bacteria. When guinea pigs were prepared by intra-abdominal injection with such antisera and tested 24 hours later by intravenous injection with autoclaved extracts of different organs and tumors of rats, they were found to be passively sensitized, so that severe or fatal anaphylaxis was obtained with extracts of brain and carcinoma 256,-a transplantable tumor of the rat which originated in the mammary gland,-and very slight or negative reactions with extracts of other tissues. The brain antigen was found to be organ-specific but not species-specific. It was present in the white matter of the central nervous system and in sciatic nerve, but was almost completely absent from the brains of fetal and newly born rats and rabbits. It was absent from the brain of the fetal guinea pig but was present very soon after birth. The amount of the specific brain antigen seemed to be dependent upon the length of the period of gestation, the stage of development of the animal at birth, and the degree of myelinization of the central nervous system. The anaphylactogen of brain broth was soluble in water and insoluble in strong ethyl alcohol. It was thermostable in neutral and slightly acid solutions but more or less thermolabile on the alkaline side of neutrality.
Phase III Study of Second-Line Chemotherapy for Advanced Non–Small-Cell Lung Cancer With Weekly Compared With 3-Weekly Docetaxel
Authors: Wolfgang Schuette, Sylke Nagel, Thomas Blankenburg, Christine Lautenschlaeger, Klaus Hans, Ernst-Wilhelm Schmidt, Ina Dittrich, Hans Schweisfurth, Ludwig Fischer von Weikersthal, Aruna Raghavachar, Angelika Reißig, Monika Serke
Journal: Journal of Clinical Oncology (2005)

Purpose A phase III study to determine whether a weekly docetaxel schedule improves the therapeutic index compared with the classic 3-weekly schedule. Patients and Methods Patients with stage IIIB-IV non–small-cell lung cancer (NSCLC) were randomly assigned to docetaxel 75 mg/m 2 on day 1 every 3 weeks (3-weekly) and 35 mg/m 2 on days 1, 8, and 15 (weekly) for ≤ eight cycles. End points included survival (primary), toxicity, and response. Results Of 215 patients enrolled, 208 (103 in the 3-weekly arm and 105 in the weekly arm) were assessable for response. At baseline, 24.5% of patients (51 out of 208) had received prior paclitaxel therapy and 43.3% of patients (90 out of 208) had been progression-free for more than 3 months after first-line therapy. After 12 months' follow-up, median survival was 6.3 months (95% CI, 4.68 to 7.84 months) with 3-weekly docetaxel and 9.2 months (95% CI, 5.83 to 12.59 months) with weekly docetaxel (P = .07) after a median of four (range, one to eight) and two (range, one to eight) treatment cycles, respectively. Overall, response rates were 12.6% v 10.5% with 3-weekly versus weekly docetaxel. Significantly fewer patients reported grade 3 to 4 toxicities with weekly docetaxel versus 3-weekly docetaxel (P ≤ .05). There were significantly lower rates of grade 3 to 4 anemia (P ≤ .05), leucopenia (P &lt; .0001), and neutropenia (P ≤ .001) with weekly versus 3-weekly treatment. No grade 3 to 4 thrombocytopenia or mucositis was reported. Conclusion Weekly docetaxel 35 mg/m 2 demonstrated similar efficacy and better tolerability than standard 3-weekly docetaxel 75 mg/m 2 and can be recommended as a feasible alternative second-line treatment option for patients with advanced NSCLC.
PWE-046 Eye Tracking Assessment Suggests Faster Time To Detection And Greater Attention Span For Dysplastic Lesions With Autofluoresence Compared To White Light Endoscopy
Authors: J Ariyaratnam, N Mohammed, V Subramanian
Journal: Gut (2014)

<h3>Introduction</h3> Surveillance endoscopy is crucial to the management of Barrett’s oesophagus to diagnose and treat dysplasia. Recent studies have confirmed that increased time of inspection of the Barrett’s mucosa increases detection rates. However increasing inspection time has both clinical and economic implications. Advanced imaging techniques like autofluoresence imaging (AFI) improves detection of dysplastic lesions, but little on known about the time taken to detect abnormalities with these modalities. <h3>Methods</h3> We presented a series of endoscopic images of dysplastic lesions within the oesophagus to novice endoscopists on a computer screen. Each of the 10 lesions was presented in white light endoscopy (WLE) and AFI modes. The subjects reviewed these images in a random order with 10 seconds for each image. They were tasked with identifying the lesion as fast as possible and fixating on it for the duration of presentation. An eye tracking system (Grinbath eye tracker, College Station Texas) was used to record eye movements of the subjects and we calculated the amount of time it took to fixate on the lesion and the percentage attention time on each lesion. <h3>Results</h3> A total of 26 novice endoscopists were recruited to the study, resulting in a total of 260 presentations of WLE images and 260 presentations of AFI images. The average time to fixation on the lesion was significantly less (p &lt; 0.05) in AFI (5.47 seconds) compared to WLE (6.17). In addition, the percentage attention span on the lesion following detection was significantly greater for AFI (58.12%) than WLE (49.96) (p &lt; 0.0005). <h3>Conclusion</h3> AFI reduces time to detection in novice endoscopists and could be a valuable training tool for trainees to improve their skills in detecting dysplasa in a time efficient manner. Advanced imaging endoscopic techniques may therefore help trainee endoscopists more than experienced endoscopists. <h3>Disclosure of Interest</h3> None Declared.
Site of Oncologic Specialty Care for Older Adolescents in Utah
Authors: Karen H. Albritton, Charles H. Wiggins, Harold E. Nelson, Jane C. Weeks
Journal: Journal of Clinical Oncology (2007)

Adolescents with cancer may access oncologic care from pediatric or adult medical centers, given overlapping age eligibility. However, some recent data suggest a benefit to adolescents with certain cancers when treated at pediatric centers or on pediatric protocols. We used a population-based registry to determine the site of care of children, adolescents, and young adults (age 0 to 24 years) with newly diagnosed cancer.From the Utah Cancer Registry 1994 to 2000, new malignant cases in patients aged 0 to 24 years were chosen; data including diagnosis, home ZIP code and sites of oncologic care were abstracted. Distance between home ZIP code and Primary Children's Medical Center (PCMC; Salt Lake City, Utah), the state's sole site of pediatric oncology care, was determined.Sixty-six percent of Utah 15- to 19-year-olds with cancer were never seen by a PCMC oncologist. Even among this narrow age range, utilization of the pediatric center dropped with each additional year of age. Not unexpectedly, few of those with epithelial malignancies in this age group were seen at PCMC. But surprisingly, 47% of the older adolescents with leukemia, 66% with brain tumors, and 71% with lymphoma never saw a pediatric oncologist. After consideration of age and diagnosis, distance the patient lived from PCMC had a negligible effect on the likelihood of an adolescent being seen there.The referral of adolescents with cancer to a pediatric oncology center diminishes greatly with age, and is moderately influenced by diagnosis and minimally by distance from center. Further study should investigate reasons for referral patterns, and impact on outcomes.
THE IMMUNOLOGICAL RELATIONSHIP OF THE CAPSULAR POLYSACCHARIDE OF TYPE XIV PNEUMOCOCCUS TO THE BLOOD GROUP A SPECIFIC SUBSTANCE
Authors: Paul B. Beeson, Walther F. Goebel
Journal: The Journal of Experimental Medicine (1939)

1. The agglutination of human erythrocytes and the precipitation of the blood group A substance by Type XIV antipneumococcus horse serum are properties of the specific anticarbohydrate immune bodies in the serum. 2. Absorption of Type XIV antipneumococcus horse serum with the homologous bacterial polysaccharide removes the agglutinins for human erythrocytes as well as the precipitins for the group A substance. 3. Absorption of Type XIV antipneumococcus horse serum with the group A substance markedly diminishes the ability of the serum to agglutinate erythrocytes of all groups. 4. Absorption of Type XIV antipneumococcus horse serum with human erythrocytes causes a marked diminution in the precipitation with group A substance. 5. The chemical and immunological relationship between the specific substances of blood group A and the Type XIV Pneumococcus is discussed.
Metformin versus clomiphene citrate for infertility in non-obese women with polycystic ovary syndrome: a systematic review and meta-analysis
Authors: M. L. Misso, M. F. Costello, M. Garrubba, J. Wong, R. Hart, L. Rombauts, A. M. Melder, R. J. Norman, H. J. Teede
Journal: Human Reproduction Update (2012)

Recent studies suggest that metformin may be more effective in women with polycystic ovary syndrome (PCOS) who are non-obese. The objective here is to determine and compare the effectiveness of metformin and clomiphene citrate for improving fertility outcomes in women with PCOS and a BMI < 32 kg/m2 (BMI 32 kg/m2 was used to allow for international differences in BMI values which determine access to infertility therapy through the public health system). Databases were searched for English language articles until July 2011. Inclusion criteria: women of any age, ethnicity and weight with PCOS diagnosed by all current criteria, who are infertile; at least 1000 mg of any type of metformin at any frequency, including slow release and standard release, compared with any type, dose and frequency of clomiphene citrate. Outcomes: rates of ovulation, live birth, pregnancy, multiple pregnancies, miscarriage, adverse events, quality of life and cost effectiveness. Data were extracted and risk of bias assessed. A random effects model was used for meta-analyses of data, using risk ratios (relative risk). The search returned 4981 articles, 580 articles addressed metformin or clomiphene citrate and four randomized controlled trials (RCTs) comparing metformin with clomiphene citrate were included. Upon meta-analysis of the four RCTs, we were unable to detect a statistically significant difference between the two interventions for any outcome in women with PCOS and a BMI < 32 kg/m2, owing to significant heterogeneity across the RCTs. Owing to conflicting findings and heterogeneity across the included RCTs, there is insufficient evidence to establish a difference between metformin and clomiphene citrate in terms of ovulation, pregnancy, live birth, miscarriage and multiple pregnancy rates in women with PCOS and a BMI < 32 kg/m2. However, a lack of superiority of one treatment is not evidence for equivalence, and further methodologically rigorous trials are required to determine whether there is a difference in effectiveness between metformin and placebo (or no treatment) or between metformin and clomiphene citrate for ovulation induction in women with PCOS who are non-obese. Until then, caution should be exercised when prescribing metformin as first line pharmacological therapy in this group of women.
Phagocytosis of antigens by Langerhans cells in vitro.
Authors: C Reis e Sousa, P D Stahl, J M Austyn
Journal: The Journal of Experimental Medicine (1993)

Dendritic cells (DC) isolated from lymphoid tissues are generally thought to be nonphagocytic in culture. It has therefore been unclear how these cells could acquire particulate antigens such as microorganisms for initiation of primary immune responses. Lymphoid DC derive in part from cells that have migrated from nonlymphoid tissues, such as Langerhans cells (LC) of skin. The ability of LC to internalize a variety of particles was studied by electron, ultraviolet, phase, and differential interference contrast microscopy, and by two-color flow cytometry. Freshly isolated LC in epidermal cell suspensions phagocytosed the yeast cell wall derivative zymosan, intact Saccharomyces cerevisiae, representatives of two genera of Gram-positive bacteria, Corynebacterium parvum and Staphylococcus aureus, as well as 0.5-3.5-microns latex microspheres. During maturation in culture, the phagocytic activity of these cells was markedly reduced. Likewise, freshly isolated splenic DC were more phagocytic than cultured DC for two types of particle examined, zymosan and latex beads. Unlike macrophages, LC did not bind or internalize sheep erythrocytes before or after opsonization with immunoglobulin G or complement, and did not internalize colloidal carbon. The receptors mediating zymosan uptake by LC were examined. For this particle, C57BL/6 LC were considerably more phagocytic than BALB/c LC and exhibited a reproducible increase in phagocytic activity after 6 h of culture followed by a decline, whereas this initial rise did not occur for BALB/c LC. These differential kinetics of uptake were reflected in the pattern of zymosan binding at 4 degrees C, and endocytosis of the soluble tracer fluorescein isothiocyanate-mannose-bovine serum albumin at 37 degrees C. Zymosan uptake by LC from both strains of mice was inhibited in the presence of mannan or beta-glucan, although to different extents, but not by antibodies specific for CR3 (CD11b/CD18). These data indicate that zymosan uptake by LC can be mediated by a mannose/beta-glucan receptor(s) that is differentially expressed in the two strains of mice and that is downregulated during maturation of LC in culture.
Sentinel Node Biopsy After Neoadjuvant Chemotherapy in Breast Cancer: Results From National Surgical Adjuvant Breast and Bowel Project Protocol B-27
Authors: Eleftherios P. Mamounas, Ann Brown, Stewart Anderson, Roy Smith, Thomas Julian, Barbara Miller, Harry D. Bear, Christopher B. Caldwell, Alonzo P. Walker, Wendy M. Mikkelson, Jay S. Stauffer, Andre Robidoux, Heather Theoret, Atilla Sovan, Bernard Fisher, D. Lawrence Wickerham, Norman Wolmark
Journal: Journal of Clinical Oncology (2005)

Purpose Experience with sentinel node biopsy (SNB) after neoadjuvant chemotherapy is limited. We examined the feasibility and accuracy of this procedure within a randomized trial in patients treated with neoadjuvant chemotherapy. Patients and Methods During the conduct of National Surgical Adjuvant Breast and Bowel Project trial B-27, several participating surgeons attempted SNB before the required axillary dissection in 428 patients. All underwent lymphatic mapping and an attempt to identify and remove a sentinel node. Lymphatic mapping was performed with radioactive colloid (14.7%), with lymphazurin blue dye alone (29.9%), or with both (54.7%). Results Success rate for the identification and removal of a sentinel node was 84.8%. Success rate increased significantly with the use of radioisotope (87.6% to 88.9%) versus with the use of lymphazurin alone (78.1%, P = .03). There were no significant differences in success rate according to clinical tumor size, clinical nodal status, age, or calendar year of random assignment. Of 343 patients who had SNB and axillary dissection, the sentinel nodes were positive in 125 patients and were the only positive nodes in 70 patients (56.0%). Of the 218 patients with negative sentinel nodes, nonsentinel nodes were positive in 15 (false-negative rate, 10.7%; 15 of 140 patients). There were no significant differences in false-negative rate according to clinical patient and tumor characteristics, method of lymphatic mapping, or breast tumor response to chemotherapy. Conclusion These results are comparable to those obtained from multicenter studies evaluating SNB before systemic therapy and suggest that the sentinel node concept is applicable following neoadjuvant chemotherapy.
Controversies in Using Lapatinib at Reduced Dosage With Food
Authors: Sabrina Trippoli
Journal: Journal of Clinical Oncology (2007)

AUTHOR’S DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST Although all authors completed the disclosure declaration, the following author(s) indicated a financial or other interest that is relevant to the subject matter under consideration in this article. Certain relationships marked with a “U” are those for which no compensation was received; those relationships marked with a “C” were compensated. For a detailed description of the disclosure categories, or for more information about ASCO’s conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors. Employment or Leadership Position: None Consultant or Advisory Role: Andrea Messori, GlaxoSmithKline-Italy (U) Stock Ownership: None Honoraria: None Research Funding: None Expert Testimony: None Other Remuneration: None
Rates of Jewish Ancestral Mutations in BRCAI and BRCA2 in Borderline Ovarian Tumors
Authors: W. H. Gotlieb, G. Ben-Baruch, E. Friedman, R. B. Bar-Sade, A. Kruglikova, G. Hirsh-Yechezkel, B. Modan, I. Novikov, B. Davidson, J. Kopolovic, M. Inbar
Journal: JNCI Journal of the National Cancer Institute (1998)

Germline mutations in the BRCA1 and BRCA2 genes are known to be associated with an increased risk of breast and epithelial ovarian cancers. Two specific mutations, 185delAG-BRCA1 and 6174delT-BRCA2, have been detected in a substantial proportion (20%-60%) of unselected Ashkenazi Jewish patients--i.e., Jewish patients of Eastern/Northern European descent--with invasive ovarian cancer and in a measurable proportion (2%) of the general Ashkenazi Jewish population. However, uncertainty exists concerning the heritable basis of borderline ovarian tumors and whether these tumors represent an early form of ultimately invasive disease. To gain insight into these issues, we determined the rates of 185delAG-BRCA1 and 6174delT-BRCA2 mutations in patients with borderline ovarian tumors.Analysis of 185delAG-BRCA1 and 6174delT-BRCA2 germline mutations was performed by use of a heteroduplex formation assay in samples from 46 consecutive patients with borderline ovarian tumors and 59 consecutive patients with invasive epithelial ovarian cancers. Forty-eight samples were also analyzed by restriction enzyme analysis for the presence of the 5382insC-BRCA1 mutation, a mutation detected in 2.2% of Ashkenazi Jewish patients with breast, but not ovarian, cancer.One (2.2%) of the 46 patient with borderline tumors was identified as a carrier of the 185delAG-BRCA1 mutation, and no patients were found to carry the 6174delT-BRCA2 mutation. Nineteen (32%) of the 59 patients with invasive ovarian cancer were found to carry one of these two mutations; 17 carried 185delAG-BRCA1 and two carried 6174delT-BRCA2 (chi2 test with continuity correction, P = .00028). None of the patients analyzed for 5382insC-BRCA1 were found to carry the mutation. In one high-risk family that included 185delAG-BRCA1 carriers, a single patient with stage IIIc borderline ovarian tumor did not carry the mutation.Invasive epithelial and borderline ovarian tumors appear to differ in their genetic predisposition and in the molecular mechanisms underlying their genesis.
A pro-fibrotic role for interleukin-4 in cardiac pressure overload
Authors: P. Kanellakis, M. Ditiatkovski, G. Kostolias, A. Bobik
Journal: Cardiovascular Research (2012)

The mechanisms underlying cardiac fibrosis in hypertension are yet to be defined, although inflammatory cells, fibroblasts, and cytokines have been implicated. Here, we investigated the role of interleukin-4 (IL-4) in cardiac fibrosis, which is elevated in the hypertensive heart. IL-4 has been shown to be pro-fibrotic in the liver and the lung, but its role in cardiac fibrosis has not been investigated.Cardiac fibrosis was induced in mice by constricting the aorta between the two carotid arteries. Fourteen days later marked left ventricular fibrosis developed together with expression of IL-4. Anti-IL-4 neutralizing antibodies attenuated this fibrosis without affecting blood pressure or expression of the transforming growth factor-beta system. The reduction in fibrosis was associated with reductions in interstitial fibroblasts and macrophages together with reductions in proliferating cells and expression of monocyte chemoattractant protein-1 (MCP-1). Since mast cells are a source of IL-4, we also assessed their role in fibrosis. Cromolyn, a mast cell inhibitor attenuated mast cell degranulation as well as IL-4 mRNA expression and cardiac fibrosis without affecting blood pressure. Treatment with Cromolyn also reduced interstitial fibroblasts and macrophages in regions of developing fibrosis as well MCP-1 expression.This study demonstrates for the first time that IL-4, most likely produced by mast cells in the heart during pressure overload, is a significant contributor to cardiac fibrosis. Targeting this cytokine may be a useful therapeutic strategy to limit cardiac fibrosis.