tbuckley/cabot-search huggingface dataset:
Local GABAergic signaling within sensory ganglia controls peripheral nociceptive transmission
Authors: Xiaona Du, Han Hao, Yuehui Yang, Sha Huang, Caixue Wang, Sylvain Gigout, Rosmaliza Ramli, Xinmeng Li, Ewa Jaworska, Ian Edwards, Jim Deuchars, Yuchio Yanagawa, Jinlong Qi, Bingcai Guan, David B. Jaffe, Hailin Zhang, Nikita Gamper
Journal: Journal of Clinical Investigation (2017)

The integration of somatosensory information is generally assumed to be a function of the central nervous system (CNS). Here we describe fully functional GABAergic communication within rodent peripheral sensory ganglia and show that it can modulate transmission of pain-related signals from the peripheral sensory nerves to the CNS. We found that sensory neurons express major proteins necessary for GABA synthesis and release and that sensory neurons released GABA in response to depolarization. In vivo focal infusion of GABA or GABA reuptake inhibitor to sensory ganglia dramatically reduced acute peripherally induced nociception and alleviated neuropathic and inflammatory pain. In addition, focal application of GABA receptor antagonists to sensory ganglia triggered or exacerbated peripherally induced nociception. We also demonstrated that chemogenetic or optogenetic depolarization of GABAergic dorsal root ganglion neurons in vivo reduced acute and chronic peripherally induced nociception. Mechanistically, GABA depolarized the majority of sensory neuron somata, yet produced a net inhibitory effect on the nociceptive transmission due to the filtering effect at nociceptive fiber T-junctions. Our findings indicate that peripheral somatosensory ganglia represent a hitherto underappreciated site of somatosensory signal integration and offer a potential target for therapeutic intervention.
Changes in patient-reported outcomes in women with breast cancer in a multicenter double-blind randomized controlled trial assessing the effect of acupuncture in reducing aromatase inhibitor-induced musculoskeletal symptoms (AIMSS).
Authors: Ting Bao, Kelly Betts, Karineh Tarpinian, Ling Cai, Jeff Gould, Stacie Jeter, Michelle Medeiros, Nancy Tait, Saranya Chumsri, Deborah Kay Armstrong, Aditya Bardia, Ming Tony Tan, Justin Stebbing, William Peter Kelleher, Elizabeth Folkerd, Mitchell Dowsett, Harvinder Singh, Claire Frances Snyder, Katherine Hanna Tkaczuk, Vered Stearns
Journal: Journal of Clinical Oncology (2012)

9103 Background: Aromatase Inhibitors (AIs) have been associated with worsening of patient related outcomes (PROs) such as AIMSS, menopausal symptoms and depression. Acupuncture has been reported to alleviate such symptoms. We hypothesized that real acupuncture (RA) would improve PROs more than sham acupuncture (SA). Methods: We collected PROs at baseline, 4, 8, and 12 weeks (wks), from women enrolled in a multi-center double blind RCT designed to assess the effect of acupuncture in reducing PROs. Patients were randomized to 8 wkly RA or SA. PROs were measured by the revised National Surgical Adjuvant Breast and Bowel Project (NSABP) menopausal symptoms questionnaire, Center for Epidemiological Studies Depression Scale (CESD), Hospital Anxiety and Depression Scale (HADS), Pittsburgh Sleep Quality Index (PSQI), Hot Flash Daily Diary, Hot Flash Related Daily Interference Scale (HFRDI) and EuroQoL survey. We measured estrogen and cytokines concentrations at baseline and wk 8. We used Wilcoxon rank sum and signed-rank tests to make comparisons between and within group, respectively. Results: We included 23 patients from RA and 24 from SA arms in the intent-to-treat analysis. We have previously reported no significant difference in reduction of AIMSS between two arms. RA caused reduction of CESD scores compared to SA (median: -2 vs 0, p = 0.057). When compared to baseline, there were statistically significant improvements at wk 8 in hot flash severity score (p=0.006), hot flash frequency (p=0.011), HFRDI (p=0.014) and NSABP menopausal symptoms (p=0.022) scores in RA arm; for EuroQoL (p=0.022), HFRDI (p=0.043) and NSABP menopausal symptoms (p=0.005) scores in SA arm. The majority of patients’ estradiol concentrations were undetectable at baseline and wk 8. Changes in other time points, data and analysis of cytokines changes will be presented at the meeting. Conclusions: Real and sham acupuncture were both associated with improvement in PROs in breast cancer patients taking AIs. We detected no significant difference in the change of PROs between real and sham acupuncture, except for CESD.
Shared decision making: Results from an interdisciplinary consulting service for prostate cancer
Authors: T. Wiegel, M. Schostak, D. Bottke, M. Müller, S. Höcht, U. Steiner, M. Schrader, K. Miller, W. Hinkelbein
Journal: Journal of Clinical Oncology (2004)

4756 Background: Locally confined prostate cancer can be treated by various treatment options (radical prostatectomy [RP] or radiotherapy [RT]) with comparable results but different possible side effects. In 2001, we established the first interdisciplinary consulting service for prostate cancer patients in Germany. The aim is to offer a comprehensive and neutral consultation on all treatment options and to make treatment recommendations. Methods: Between 05/01 and 04/03, 362 pts. presented to the consulting service. 2 questionnaires were used. The first one contained epidemiological questions and questions covering information already available on the topic. It also examined fears about the disease / treatment options. The second one was given 2 weeks after the consultation to evaluate the treatment decision and determine the patient's satisfaction with the consultation. Results: 334 cases were assessable. All pts. had already obtained information about the disease / possible treatment options and wished to be involved in the decision-making process. Nearly all of them had a great fear of possible side effects. Such a comprehensive consultation is time-consuming (35 min.) but largely received a very positive assessment in that 66% found it helpful or very helpful. Pts. felt they had been completely informed in 92% of the cases. Only 10% had still failed to make a decision after 2 weeks. 115 pts. had stage T1c, PSA <10 ng/ml and Gleason ≤7. In these cases an equivalent recommendation for RP or RT was given. 43% decided on RP and 43% on RT. Only 16% remained undecided. The histological examination of RP specimens of the pts. who had decided on RP showed a decrease in the rate of extracapsular disease extension (≥T3) from 38 to 20% during the observation period. Conclusions: The change to more cooperation between the different specialities has made the process of deciding on an appropriate treatment much easier for the patient. The consultation enables better selection of individual treatment modalities and their possible side effects from the point of view of both the patients and the attending physicians. In this study, patients choose either RP or RT with equal frequency. No significant financial relationships to disclose.
Rapid Early Growth Is Associated With Increased Risk of Childhood Type 1 Diabetes in Various European Populations
Journal: Diabetes Care (2002)

OBJECTIVE—To confirm that early growth is associated with type 1 diabetes risk in European children and elucidate any role of infant feeding. RESEARCH DESIGN AND METHODS—Five centers participated, each with a population-based register of type 1 diabetes diagnosed at &amp;lt;15 years of age. Control subjects were randomly chosen from population registers, schools, or polyclinics. Growth data were obtained from routine records and infant feeding information from parental questionnaire or interview. Patient/control subject differences in mean standard deviation score (SDS) were obtained for each center and pooled. Odds ratios (ORs) were pooled by the Mantel-Haenszel method, and logistic regression was used to adjust for confounders. RESULTS—Growth data were available for 499 patients and 1,337 control subjects. Height and weight SDS were significantly increased among patients from 1 month after birth, the maximum differences of 0.32 (95% CI 0.14–0.50) and 0.41 (0.26–0.55), respectively, occurring between 1 and 2 years of age. Significant excesses in BMI SDS were observed from 6 months of age, with the largest difference of 0.27 (0.10, 0.44) evident between 1 and 2 years. Breast-feeding was associated with reduced disease risk, OR 0.75 (0.58–0.96). Introduction of cow’s milk, formula, or solid foods before 3 months was not associated with significant risk elevation. CONCLUSION—Increased early growth is associated with disease risk in various European populations. Any role of infant feeding in this association remains unclear.
A Single-Arm PHASE 2A Study of NM-IL-12 (rHu-IL12) in Patients with Mycosis Fungoides-Type CTCL (MF) Undergoing Low-Dose TOTAL Skin Electron BEAM Therapy (LD-TSEBT)
Authors: Youn H Kim, Richard T. Hoppe, Alain H Rook, Amit Maity, Larisa J Geskin, David P Horowitz, Genet Finnegan, Michael Khodadoust, Wen-Kai Weng, Analuisa Lares, Eric Ki Jun Hong, Marie Buchanan, Vernon Ma, Hue Kha, Chris E Lawrence, Vladimir Vainstein, Lena A Basile
Journal: Blood (2016)
A Phase II Study of Dovitinib in Patients with Recurrent or Metastatic Adenoid Cystic Carcinoma
Authors: Patrick M. Dillon, Gina R. Petroni, Bethany J. Horton, Christopher A. Moskaluk, Paula M. Fracasso, Michael G. Douvas, Nikole Varhegyi, Snjezana Zaja-Milatovic, Christopher Y. Thomas
Journal: Clinical Cancer Research (2017)

Abstract Purpose: Genetic and preclinical studies have implicated FGFR signaling in the pathogenesis of adenoid cystic carcinoma (ACC). Dovitinib, a suppressor of FGFR activity, may be active in ACC. Experimental Design: In a two-stage phase II study, 35 patients with progressive ACC were treated with dovitinib 500 mg orally for 5 of 7 days continuously. The primary endpoints were objective response rate and change in tumor growth rate. Progression-free survival, overall survival, metabolic response, biomarker, and quality of life were secondary endpoints. Results: Of 34 evaluable patients, 2 (6%) had a partial response and 22 (65%) had stable disease &amp;gt;4 months. Median PFS was 8.2 months and OS was 20.6 months. The slope of the overall TGR fell from 1.95 to 0.63 on treatment (P &amp;lt; 0.001). Toxicity was moderate; 63% of patients developed grade 3–4 toxicity, 94% required dose modifications, and 21% stopped treatment early. An early metabolic response based on 18FDG-PET scans was seen in 3 of 15 patients but did not correlate with RECIST response. MYB gene translocation was observed and significantly correlated with overexpression of MYB but did not correlate with FGFR1 phosphorylation or clinical response to dovitinib. Conclusions: Dovitinib produced few objective responses in patients with ACC but did suppress the TGR with a PFS that compares favorably with those reported with other targeted agents. Future studies of more potent and selective FGFR inhibitors in biomarker-selected patients will be required to determine whether FGFR signaling is a valid therapeutic target in ACC. Clin Cancer Res; 23(15); 4138–45. ©2017 AACR.
Heat shock protein 70-based vaccine stimulates both innate and adaptive immunity against chronic myeloid leukemia
Authors: Z. Li, Y. Qiao, B. Liu, P. Srivastava
Journal: Journal of Clinical Oncology (2004)

2515 Background: HSP70 chaperones both proteins and antigenic peptides. Vaccination with tumor-derived HSP70-peptide complexes elicits anti-tumor immunity in murine models. We have earlier reported that HSP70 vaccines can be effectively produced from peripheral blood mononuclear cells (PBMCs) of patients with chronic myeloid leukemia (CML) in chronic phase. Moreover, eight weekly injections of 50 μg autologous HSP70 vaccines were associated with no grade II or higher toxicity in any patients and with clinical efficacies in 11 out of 17 patients. In the present study, the immunological responses to this vaccine were studied. Methods: All patients in the study had either cytogenetic or molecular evidence of diseases, despite Imatinib Mesylate, prior to the study entry. Peripheral blood was obtained, before the 1st and 5th vaccines, and two weeks after the 8th vaccine. IFNγ-producing effector cells in PBMCs were measured by an ELISPOT assay using a variety of targets, including HLA negative but Bcr/Abl+ K562 cell lines, HSP70-peptide complexes or K562 lysates. A pan-HLA class I specific antibody W6/32 was used to determine if IFNγ production was MHC restricted or not. Results: The frequency of IFNγ-producing cells in the PBMCs, in response to HSP70-peptide complexes, was increased in nine out of 12 patients analyzed. This activity was significantly blocked by W6/32, indicating that peptides bound to HSP70 can be cross-presented to HLA class I to activate CD8+ T cells. The incomplete blockage by W6/32 indicates that HSP70 can stimulate IFNγ production by other cells, in a peptide-independent manner. Indeed, natural killer (NK) cell activity post vaccinations, as measured against the standard NK target K562, increased markedly in 12 out of 15 patients. We have also confirmed an increased frequency of CML-specific and HLA class I-restricted T cells using K562 cell lysates as targets. Conclusion: The autologous HSP70-based vaccine induces both NK and CML-specific T cell immunity in a majority of patients. The remarkable immunologic activity of HSP70 suggests that it has adjuvant therapeutic values for CML. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Antigenics Antigenics Antigenics
Polymorphisms in the estrogen pathway, estrogen receptor alpha gene (<i>ESR1</i>), daily cycling estrogen and mammographic density.
Authors: FrÃ¶ydis Nyborg Fjeldheim, Hanne Frydenberg, Vidar Gordon Flote, Anne McTiernan, Peter T Ellison, Emily S Barrett, Grazyna Jasienska, Karen W Makar, Giske Ursin, Erik Andreas Wist, Inger Thune
Journal: Journal of Clinical Oncology (2015)

1551 Background: Single nucleotide polymorphisms (SNPs) involved in the estrogen pathway and SNPs in the estrogen receptor alpha gene (ESR1, 6q25), have been linked to breast cancer development. However, whether there is an association between daily estradiol levels, SNPs in ESR1and premenopausal mammographic density phenotypes has not yet been ascertained. Methods: Estradiol was assessed in daily saliva samples throughout an entire menstrual cycle, in 202 healthy premenopausal women (aged 25-35), participating in the Norwegian Energy Balance and Breast Cancer Aspects (EBBA) I study. DNA was genotyped using the Illumina Golden Gate platform. Mammograms were taken between days 7-12 of the menstrual cycle, and digitized mammographic density phenotypes were assessed using a computer-assisted method (Madena). Multivariable regression models were used to study the association between SNPs in ESR1, premenopausal mammographic density phenotypes and daily cycling estradiol. Results: We observed inverse linear associations between the minor alleles of 8 of 34 measured SNPs (rs3020364, rs2474148, rs12154178, rs2347867, 6927072, rs2982712, 3020407, rs9322335) and percent mammographic density (p values: 0.002 - 0.026), and these associations were strongest in lean women (BMI, ≤ 23.6 kg/m2.). The odds of above-median percent mammographic density ( > 28.5%) among women with major homozygous genotypes were 3-6 times higher than those of women with minor homozygous genotypes in 7 SNPs. Women with rs3020364major homozygous genotype had an OR of 6.46 for above-median percent mammographic density (95% Confidence Interval 1.61, 25.94) when compared to women with the minor homozygous genotype. These associations were not observed in relation to absolute mammographic density. No linear associations between SNPs and daily cycling estradiol were observed. Conclusions: Our results support an association between eight selected SNPs in the ESR1 gene and percent mammographic density. The results need to be replicated in larger studies.
Continuing to work while receiving cancer treatment: A financial or a symbolic issue?
Authors: Gerard Ganem, Herve L. Naman, Nadine Dohollou, Thomas Facchini, Yvan Coscas, Eric-Charles Antoine, Alain Lortholary, Stephanie Catala, Stephane Jacquot, Christine Lhomel, François Eisinger
Journal: Journal of Clinical Oncology (2013)

6603 Background: As improved cure rates lead to longer life expectancy, occupational concerns during and after cancer treatment become important. The advent of new drugs with fewer side effects will increase the profile of this issue. We carried out a field survey to explore the question. Methods: We questioned 97 oncologists, and a subgroup of 216 patients treated for breast cancer who were working at the time of diagnosis and who wanted to continue to do so during at least part of the treatment period. Results: Data Collected from Patients: In total, 208 patients (96%) were satisfied or very satisfied with their jobs. Only 68 (31%) were able to achieve the goal of working without interruption while being treated (physicians estimated that figure at only 11%). For the remaining women, who did stop working (69%), the median number of days off work was 59. Data Collected from Physicians: A total of 87 physicians (89%) stated that having information regarding working conditions is very important when counseling patients about whether they could continue to work. Comparison of the answers given by patients and physicians: 36% of physicians thought that the initiative in addressing the work/job issue was taken primarily by themselves, while 53% felt it came from the patient. The patient perspective was different: 61% of patients thought they took the initiative themselves and only 13% of them thought the physician took the lead. The main reason behind the desire to continue working is thought by 56% of physicians to be “Financial gain”; while for patients it is “To feel the same” (42%). A total of 90 (92%) physicians feared that those patients continuing to work would face at least one type of medical difficulty; only 143 (66%) patients shared this fear. Lastly, although 94% of the physicians have access to psychological or psychiatric support workers at the health care center, only 62% have access to a social worker. Conclusions: Of the patients who really wanted to work while being treated for breast cancer, only 31% could achieve that goal without any interruption. There is also a difference of perception regarding patient motivation, with physicians believing that the reasons are mainly financial while the patients see it as more of a symbolic issue.
Treatment Restarting After Discontinuation of Adjuvant Hormone Therapy in Breast Cancer Patients
Authors: Wei He, Karin E. Smedby, Fang Fang, Henrik Olsson, Sara Margolin, Per Hall, Kamila Czene
Journal: JNCI Journal of the National Cancer Institute (2017)

Over half of breast cancer patients discontinue their adjuvant hormone therapy, permanently or temporarily. We aimed to identify predictors of treatment restarting after discontinuation of adjuvant hormone therapy and to test the hypothesis that treatment restarting is associated with better breast cancer outcomes.We conducted a population-based cohort study by linking data from the Stockholm-Gotland Breast Cancer Register, the Swedish Prescribed Drug Register, and a self-reported questionnaire. We followed women diagnosed with breast cancer (Stockholm, Sweden, 2005-2008) from their first prescription of tamoxifen or aromatase inhibitors through January 31, 2015, and categorized them as continuers (n = 1 607), restarters (n = 953), and nonrestarters (n = 511) of adjuvant hormone therapy. All statistical tests were two-sided.Factors that decrease the likelihood of treatment restarting included younger age (<50 years), higher Charlson Comorbidity Score (≥2), smaller tumor size (<20 mm), human epidermal growth factor receptor 2 negative, lymph node negative, family history of breast cancer negative, using hormone therapy, using symptom relieving drugs, and switching therapy between tamoxifen and aromatase inhibitors. Restarting adjuvant hormone therapy was statistically significantly associated with prolonged disease-free survival, with an adjusted hazard ratio of 0.61 (95% confidence interval = 0.43 to 0.87, P = .006) for restarters vs nonrestarters.Our study provides-for the first time to our knowledge-evidence that restarting adjuvant hormone therapy is associated with better breast cancer outcomes. Clinicians now have further evidence to encourage patients to restart their treatment after discontinuation of adjuvant hormone therapy.
Bladder-sparing treatment using combined chemotherapy and radiotherapy for muscle-invading bladder cancer
Authors: R. Noguchi, K. Oka
Journal: Journal of Clinical Oncology (2004)

4665 Background: Five-year survival for invasive bladder cancer is up to about 50% in many recent reports. Laboratory studies have suggested cisplatin and irradiation might act synergistically. To improve survival, We have performed combination therapy of irradiation and modified MVAC. Methods: METHODS; Between March 1995 and December 2003, 22 patiens of invasive bladder cancer(T2;10, T3;8, T4;4) were enrolled in the study. In all patients, muscle invasion was proven by trans-urethral biopsy. Treatment regimen consisted of combination of irradiaton and chemotherapy. Irradiation started one week before chemotherapy and was performed for 2 weeks(2.0 Gy/fr, total 10 fr). Chemotherapeic regimen was modified MVAC (30mg/m2 methotrexate on day 1, followed by 3mg/m2depends on document reviewvinblastine, 20mg/m2depends on document reviewdoxorubicin or epirubicin, and 70 mg/m2depends on document reviewcisplatin on day 2). All patients received 2–3 cycles. The total dose of irradiation to tumor was 40–60 Gy. After combination therapy, transurethral resection was performed. Results: All twenty-two patients had not performed cystectomy, because of no cancer cells in muscle layer. One patient died of metastasis after 6 months. Cause-specific / over-all 5-year survival rate was 95.2 / 77.4 % (mean follow up= 41 months). 86.4 % of all patients preserved their bladders intact. Severe toxicity has consisted of bone marrow suppression(18 pt.), and vesico-Sigmoid colon fistula(1 pt.). No patients died of toxicity. This combination therapy was well tolerated. Conclusions: Our result suggests combination therapy of irradiation and chemothrapy is much effective for muscle invading bladder cancer. In selected patients with musle-invading bladder cancer, functionig bladder will be preseved in the near future. No significant financial relationships to disclose.
Questioning a Taboo
Authors: Larry B. Mauksch
Journal: JAMA (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal