tbuckley/cabot-search huggingface dataset:
Brief Report: Intraarticular Sprifermin Not Only Increases Cartilage Thickness, but Also Reduces Cartilage Loss: Location‐Independent Post Hoc Analysis Using Magnetic Resonance Imaging
Authors: Felix Eckstein, Wolfgang Wirth, Ali Guermazi, Susanne Maschek, Aida Aydemir
Journal: Arthritis & Rheumatology (2015)

To determine whether an anabolic drug (sprifermin) is capable of reducing cartilage loss wherever it occurs in a given knee, using a subject-specific, location-independent analysis of cartilage change in patients with knee osteoarthritis (OA).Study participants (n = 168; ages ≥40 years, 69% women) had symptomatic femorotibial OA not confined to the medial compartment. Sprifermin (10, 30, or 100 μg) or placebo was injected intraarticularly 3 times over 3 weeks, both after randomization (baseline) and 3 months later. Coronal magnetic resonance images were acquired at baseline and 3, 6, and 12 months after treatment. The femorotibial cartilage of each subject was segmented, and changes in cartilage thickness were computed across 16 subregions. Location-independent post hoc analysis was used to compute summary scores of negative and positive changes in the subregions, summarized as the total cartilage thinning sum score (ThCTnS) and the total cartilage thickening sum score (ThCTkS), capturing change in either direction in each knee. Ordered values of the magnitude of subject-specific subregional changes in thickness were determined. The ThCTnS and ThCTkS in each sprifermin dose group at 12 months of followup were compared with the values in the matched placebo groups, using the Wilcoxon-Mann-Whitney test.The mean ± SD ThCTnS was -591 ± 617 μm (median -360 μm, Q1/Q3 = -820/-200 μm) in patients treated with 100 μg sprifermin (n = 57), and -921 ± 777 μm (median -745 μm, Q1/Q3 = -1,190/-380 μm) in patients given placebo (n = 18). The mean difference in the ThCTnS between the 100-μg sprifermin group and the placebo group was 331 μm (95% confidence interval [95% CI] 24, 685), a difference that was statistically significant (P = 0.03). The mean difference in the ThCTkS in the 100-μg sprifermin group compared with the placebo group was 237 μm (95% CI 34, 440), also a statistically significant difference (P = 0.028).Sprifermin not only increases cartilage thickness, but also reduces cartilage loss. Subject-specific, location-independent analysis of both cartilage thinning and thickening represents a sensitive and informative approach for studying the effects of disease-modifying OA drugs.
Young male football player with shoulder pain 2 years after traumatic shoulder injury
Authors: G Ansede, J C Lee, J C Healy, A W Mitchell
Journal: British Journal of Sports Medicine (2010)

A 23-year-old amateur football player sustained a minor fall during a training session in which he was tackled while running at low speed and fell sideways onto his flexed elbow. He sustained a traumatic injury to the non-dominant right shoulder, which had an optimal recovery after outpatient management for 6 months. A plain radiograph of the shoulder shortly after this initial injury was taken (figure 1A,B).



Figure 1 
(A) Frontal and (B) trans-scapular radiographs of an anterior glenohumeral dislocation. The humeral head lies anterior and inferior to the glenoid and the articular surfaces are not congruent. A Hill–Sachs deformity (arrow) is seen as flattening of the superoposterior aspect of the humeral head. (C) Frontal and (D) lateral radiographs of a normal shoulder showing congruence of the glenohumeral articular surfaces (double arrows) and superimposed humeral head and glenoid on the oblique lateral view (oval perimeter).



Two years after management of the original injury, he presented complaining of a 1-year history of a progressively more prominent subjective sensation of instability and intermittent shoulder pain on extremes of range of motion, particularly when the arm was abducted and/or externally rotated. A magnetic resonance (MR) arthrogram was then performed to aid in the diagnosis (figure 2).



Figure 2 
Fat saturated T1-weighted magnetic resonance arthrographic image revealing a minimally displaced and avulsed antero-inferior labrum in keeping with a Bankart lesion (arrow). The presence of the subscapularis tendon (arrowhead) locates this image below the equator of the humeral head.



The medical history was unremarkable and he was not taking any regular medication.

On physical examination, the patient was an otherwise healthy young man with a slightly reduced shoulder range …
Paclitaxel, an Active Agent in Nonsquamous Carcinomas of the Uterine Cervix: A Gynecologic Oncology Group Study
Authors: John P. Curtin, John A. Blessing, Kenneth D. Webster, Peter G. Rose, Allan R. Mayer, Wesley C. Fowler, John H. Malfetano, Ronald D. Alvarez
Journal: Journal of Clinical Oncology (2001)

PURPOSE: A phase II trial of paclitaxel was initiated in advanced nonsquamous carcinoma of the cervix to determine its activity in patients who had failed standard chemotherapy. PATIENTS AND METHODS: Eligible patients had at least one measurable lesion. The starting dose of paclitaxel was 170 mg/m 2 (135 mg/m 2 for patients with prior pelvic radiation) given as a 24-hour continuous intravenous infusion with courses repeated every 3 weeks. Dose escalation to 200 mg/m 2 and de-escalation to 110 mg/m 2 were allowed based on adverse effects. RESULTS: In this trial, 42 assessable patients were initially entered onto the study, and 13 responses were seen; four patients had a complete response, and nine patients had a partial response. The overall response rate was 31%. The primary and dose-limiting toxicity was neutropenia. CONCLUSION: The response rate to paclitaxel exceeds the rates reported using other single agents in nonsquamous carcinoma of the cervix.
An <i>In Vivo</i> Method to Identify microRNA Targets Not Predicted by Computation Algorithms: p21 Targeting by miR-92a in Cancer
Authors: Xiaoping Su, Huaming Wang, Wei Ge, Mingjin Yang, Jin Hou, Taoyong Chen, Nan Li, Xuetao Cao
Journal: Cancer Research (2015)

microRNA (miRNA) dysregulation is involved in the development and progression of various human cancers, including hepatocellular carcinoma (HCC). However, how to identify the miRNAs targeting specific mRNA in cells is a significant challenge because of the interaction complexity and the limited knowledge of rules governing these processes. Some miRNAs are not predictable by current computer algorithms available. Here, using p21 mRNA as target, we established a new method, called miRNA in vivo precipitation (miRIP), to identify which kind of miRNAs can actually bind to the specific mRNA in cells. Several unpredictable miRNAs that bound p21 mRNA in HepG2 and PC-3 cells were identified by the miRIP method. Among these miRNAs identified by miRIP, miR-92a was found and confirmed to interact robustly with p21 mRNA, both in HepG2 and PC-3 cells. miR-92a was found to be remarkably increased in HCC tissues, and higher expression of miR-92a significantly correlated with lower expression of p21, which is related to poor survival of HCC patients. Moreover, inhibition of miR-92a could significantly suppress HCC growth in vitro and in vivo by upregulating p21. Together, miR-92a, which is identified by miRIP, is functionally shown to be associated with HCC growth as an oncogenic miRNA by inhibiting expression of targeting gene p21. In addition, several unpredictable miRNAs that target STAT3 mRNA were also identified by the miRIP method in HepG2 cells. Our results demonstrated that the miRIP approach can effectively identify the unpredictable but intracellular existing miRNAs that target specific mRNA in vivo.
Factors influencing mutation at the hprt locus in T-lymphocytes: women treated for breast cancer.
Authors: Branda Rf, O'Neill Jp, Sullivan Lm, Albertini Rj
Journal: Cancer Research (1991)

Abstract  Forty-nine women with breast cancer were enrolled in a prospective, longitudinal study of the genetic damage caused by treatment. Assays of mutant frequency at the  hprt  locus in peripheral blood lymphocytes were performed at approximately 6-month intervals for 2 years. Treatment consisted of surgery alone or additional tamoxifen, radiotherapy, or chemotherapy in various combinations. At 6 months, there was an elevation of mean mutant frequency compared to initial values ( P  = 0.004) which persisted for as many as 2 years. A significant elevation at 6 months occurred only in the group of women who received combination chemotherapy ( P  = 0.005). Within this group, 5 of 15 patients had striking elevations of mutant frequency following chemotherapy (>3 SD). Three of these 5 women had serum folate levels in the deficient range, while only one of 9 patients with lesser responses to chemotherapy were folate deficient. The change in mutant frequency after chemotherapy was inversely related to serum folate levels ( P  = 0.05) and to the number of years of smoking cigarettes ( P  = 0.01). We conclude that of the various modalities used to treat breast cancer, only chemotherapy was accompanied by a high risk of somatic mutation. A subset of patients manifested substantial increases in mutant frequency, often in association with low serum folate levels.
Evolution of the alpha-crystallin/small heat-shock protein family.
Authors: W W de Jong, J A Leunissen, C E Voorter
Journal: Molecular Biology and Evolution (1993)

The common characteristic of the alpha-crystallin/small heat-shock protein family is the presence of a conserved homologous sequence of 90-100 residues. Apart from the vertebrate lens proteins--alpha A- and alpha B-crystallin--and the ubiquitous group of 15-30-kDa heat-shock proteins, this family also includes two mycobacterial surface antigens and a major egg antigen of Schistosoma mansoni. Multiple small heat-shock proteins are especially present in higher plants, where they can be distinguished in at least two classes of cytoplasmic proteins and a chloroplast-located class. The alpha-crystallins have recently been found in many tissues outside the lens, and alpha B-crystallin, in particular, behaves in many respects like a small heat-shock protein. The homologous sequences constitute the C-terminal halves of the proteins and probably represent a structural domain with a more variable C-terminal extension. These domains must be responsible for the common structural and functional properties of this protein family. Analysis of the phylogenetic tree and comparison of the biological properties of the various proteins in this family suggest the following scenario for its evolution: The primordial role of the small heat-shock protein family must have been to cope with the destabilizing effects of stressful conditions on cellular integrity. The alpha-crystallin-like domain appears to be very stable, which makes it suitable both as a surface antigen in parasitic organisms and as a long-living lens protein in vertebrates. It has recently been demonstrated that, like the other heat-shock proteins, the alpha-crystallins and small heat-shock proteins function as molecular chaperones, preventing undesired protein-protein interactions and assisting in refolding of denatured proteins. Many of the small heat-shock proteins are differentially expressed during normal development, and there is good evidence that they are involved in cytomorphological reorganizations and in degenerative diseases. In conjunction with the stabilizing, thermoprotective role of alpha-crystallins and small heat-shock proteins, they may also be involved in signal transduction. The reversible phosphorylation of these proteins appears to be important in this respect.
Long-term effect in outcomes of intensified primary chemotherapy in poor prognosis LABC T4 patients: Results of a multicenter Italian study
Authors: M. Ionta, F. Atzori, D. Nonnis, M. Deidda, A. Contu, A. Farris, A. Catino, S. Palmeri, L. Minerba, B. Massidda
Journal: Journal of Clinical Oncology (2006)

10518 Background: Recent data showed that anthracycline-based chemotherapy with increased dose-intensity improves clinical outcomes as compared to conventional regimens in adjuvant setting, particularly in high risk patients with HR negative tumors. Nevertheless dose-intensity in neoadjuvant setting remain controversial. The aim of this study was to evaluate the outcome between two different primary regimens and, furthermore, among soubgroups identified by HR status. Methods: Between 1996 and 2001, 72 consecutive LABC patients, (77% T4abc; 23% T4d; 88% axillary nodes involvement) median age 51 (29–70), ER neg 39%; PgR neg 71%, were treated with PEV regimen (cisplatin 50 mg/m 2 ; epirubicin 100 mg/m 2 ; vinorelbine 25 mg/m 2 ) as primary chemotherapy. The regimen was delivered with different number of cycles and treatment intervals (3 wks × 4 cycles in the first 24 pts as PEV21 × 4; 2 wks × 6 cycles in the subsequent 48 pts as PEV14 × 6); the entire treatment in both groups lasted 12 weeks. All 72 patients received adjuvant CMF, RT and Hormonal treatment when indicated. Results: after a median follow up of 76 months (46–111), higher DFS and OS were observed in the intensified PEV14 × 6 group as compared to the counterpart (69% vs 42% p = 0.02 and 78% vs 58% p = 0.05 respectively). Statistically better DFS and OS were observed in the group ER/ PgR negative which received intensified PEV 14 × 6, whereas no statistically difference was found among ER/ PgR postive patients, regardless of the type of regimen. Conclusions: Our results suggest that primary intensified chemotherapy is associated with a better clinical outcome in poor prognosis LABC T4 patients,and that HR negative tumors benefit greatly from intensified regimen. Further prospective randomized studies are needed to confirm our data. [Table: see text] No significant financial relationships to disclose.
Neoplasms in Persons Treated With X Rays in Infancy for Thymic Enlargement. A Report of the Third Follow-Up Survey&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Louis H. Hempelmann, James W. Pifer, George J. Burke, Roger Terry, Wendell R. Ames
Journal: JNCI Journal of the National Cancer Institute (1967)

In upstate New York, 2,878 persons given X-ray treatment in infancy for thymic enlargement and their 5,006 untreated siblings were surveyed by mail in 1963 for the third time to determine the current incidence of neoplasms and mortality. Questionnaires revealed that an excess number of tumors had developed in the treated population since last surveyed (1959). Thyroid neoplasms, including 5 carcinomas, accounted for 11 of the 26 new tumors. No new cases of leukemia or osteochondroma occurred after age 20. A definite dose response was established for both thyroid and “pooled” extrathyroid neoplasms. The incidence of thyroid neoplasms was much higher in persons treated with anterior and posterior (AP) X-ray ports than in those treated with anterior (A) ports only. Presumably, this was because AP treatment usually irradiated the gland with the primary X-ray beam, whereas A treatments usually exposed the gland to smaller doses of scattered X rays. The magnitude of the thyroid dose could not be correlated with (a) the latent period between exposure and tumor development, or (b) whether any given lesion was malignant or benign. The incidence curve for thyroid neoplasms rises sharply in the 10–19 year category, flattens in the 20–29 year category, and that for carcinomas may actually decline after age 20. Five of the six thyroid carcinomas occurring under age 15 were in males. All 19 persons with thyroid carcinomas, including 9 with metastases, responded well to therapy and were healthy at the time of survey. Plans for future study of the high-risk and low-risk groups in the irradiated population are discussed.
Itching for a Diagnosis
Authors: Libby Schaefer, Anand Vaidya, Helmut G. Rennke, Julie Paik
Journal: New England Journal of Medicine (2015)

A 58-year-old black woman presented to an urgent care clinic with pruritus, which had developed in the preceding 2 weeks along with fatigue, dizziness, and decreased appetite. There was no visible rash. The diffuse body itch had progressively worsened during this period, particularly at night, and the itching interfered with her ability to sleep. The patient reported . . .
Tumor-Specific Vaccine Containing &lt;italic&gt;Mycobacterium bovis&lt;/italic&gt; and Tumor Cells: Safety and Efficacy
Authors: Gerald L. Bartlett, Berton Zbar
Journal: JNCI Journal of the National Cancer Institute (1972)

The ability of bacillus Calmette-Guérin (BCG) to ausment the immunogenicity of a poorly immunogcnic, syngeneic ascites hepatoma (line 10 ) of strain-2 guinea pigs was studied in a model system characterized by simultaneous contralateral injection of immunizing (vaccine) and challenge (living tumor cell) preparations. Several immunization procedures were compared to determine conditions optimal for vaccine safety and therapeutic potency. Under the best conditions, palpable malignant tumors at the challenge site (up to 15-mm diameter) ceased growth and regressed completely due to a systemic tumor-specific immune response. Effective vaccines contained living BCG and viable line-10 cells. Vaccines with irradiated (12,000 R) tumor cells were as effective as those with unirradiated cells. Vaccines containing unirradiated tumor cells were occasionally tumor-igenic in animals with tumor at a distant site. Use of repeated vaccine injections or a larger dose of tumor cells in the vaccine did not improve the therapeutic effect. Vaccines not affecting growth of the challenge tumor were line-10 cells emulsified in complete Freund's adjuvant, irradiated line-10 cells without BCG, or line-1 cells (antigenically distinct tumor) mixed with BCG.
Abstract 4182: Bioinformatic analysis identifies polo-like kinase as a therapeutic target in small-cell lung cancer
Authors: Gary Wildey, Yanwen Chen, Ian Lent, Lindsay Stetson, John Pink, Jill Barnholtz-Sloan, Afshin Dowlati
Journal: Cancer Research (2014)

Abstract Small cell lung cancer (SCLC) represents 15% of all lung carcinomas and is typically diagnosed when the disease has metastasized. Although most SCLC is initially sensitive to chemotherapy regimens, relapse is common and the survival benefit of second-line therapies, such as topotecan, is also limited. There are currently no molecular targeted approaches to treat SCLC similar to those used successfully against non-small-cell lung cancer (NSCLC). This failure is partly attributable to the empiric nature of these efforts. Thus, a more systematic approach to drug discovery for SCLC may lie in mining available databases on the drug sensitivities of SCLC cell lines. In this regard, two comprehensive studies recently published in Nature, the Cancer Cell Line Encyclopedia (CCLE) and the Cancer Genome Project (CGP), examined the drug sensitivities of cancer cell lines and attempted to link these to their genomic profiles. In the present study we have extracted data on SCLC cell lines from these two studies and mined it for new, promising therapeutic agents for SCLC. Our analyses demonstrate that the drug sensitivity of the SCLC cell lines reflects what is observed clinically for metastatic SCLC tumors. That is, most cells were extremely sensitive to topoisomerase (camptothecin) and microtubule (vinblastine and docetaxel) inhibitors, by contrast many tyrosine kinase inhibitors (erlotinib, sorafenib and imatinib) were ineffective. Importantly, we identified heat shock proteins (HSP), cyclin-dependent kinases (CDK) and polo-like kinases (PLK) as attractive molecular targets that have received little/no attention in clinical trials of SCLC. We further developed a gene signature for PLK inhibitor sensitivity and validated it in untested SCLC cell lines. This gene signature was incorporated into circos plots to yield a comprehensive view of how transcriptional, copy number and mutational elements affect PLK sensitivity in SCLC cell lines. Citation Format: Gary Wildey, Yanwen Chen, Ian Lent, Lindsay Stetson, John Pink, Jill Barnholtz-Sloan, Afshin Dowlati. Bioinformatic analysis identifies polo-like kinase as a therapeutic target in small-cell lung cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4182. doi:10.1158/1538-7445.AM2014-4182
Single nucleotide polymorphism of PSMA6 gene in Lithuanian patients with asthma
Authors: Zivile Zemeckiene, Edita Gasiuniene, Astra Vitkauskiene, Brigita Sitkauskiene, Raimundas Sakalauskas
Journal: European Respiratory Journal (2013)

Introduction: Asthma is a chronic airway inflammatory disorder which morbidity is increasing worldwide, but the predisposing factors are not well known. Recently much attention has been given to the association between polymorphism of proteasome encoding genes and various diseases.  Aim: The aim of this study was to evaluate single nucleotide polymorphism (SNP) of  PSMA6  gene in Lithuanian subjects with asthma and healthy subjects.  Methods: Patients with asthma (n=145; mean age 46.4±15.3yrs) and healthy subjects (n=150; mean age 41.0±14.4yrs) as a control group were involved in this study. Asthma was diagnosed according to GINA criteria. DNA from peripheral blood was extracted using Qiagen (Germany) DNA blood mini kit standardized protocol. SNPs were evaluated using allele specific amplification and cleaved amplified polymorphic sequence methods. These SNPs of  PSMA6  gene were evaluated: rs2277460 in promoter region (-110 from the translation start, -110C>A) and rs1048990 in 59UTR region (-8 from the translation start, -8C>G).  Results: The frequency of A allele (-110C>A) polymorphism in patients with asthma was 12.8% and 9.3% in healthy subjects. CA genotype was also found more frequently in asthmatics (25.0% vs 18.7%), but there was no association between asthma and this genotype (χ2=1.94; p=0.16). The G allele (-8C>G) was found in 18.1% of asthmatics and in 15.3% of healthy subjects. The frequency of genotypes CG, GG did not significantly differ between studied groups (in patients with asthma: CG – 28.0%, GG – 4.0%; in healthy subjects – 28.0%, 1.3%, respectively).  Conclusions: The study showed that some SNPs of  PSMA6  gene are present more frequently in patients with asthma than in healthy subjects.