tbuckley/cabot-search huggingface dataset:
Induction chemotherapy with carboplatin and weekly paclitaxel followed by concomitant chemoradiation in locally advanced non-small cell lung cancer
Authors: A. Aydiner, E. Topuz, Y. Eralp, E. Kaytan, E. N. Oral, A. Kizir
Journal: Journal of Clinical Oncology (2004)

7270 Background: The aim of this study is to evaluate the efficacy of an induction regimen consisting of carboplatin and weekly paclitaxel followed by concomitant chemotherapy and thoracic irradiation in patients with NSCLC. Methods: Twenty-four patients with stage III NSCLC, who were not amenable to curative surgery and ECOG PS ≤2 were administered an induction combination consisting of carboplatin at an AUC 6 mg.ml/min on D1 and 21 and weekly paclitaxel at 100 mg/m2 for 5 consequtive weeks starting on D1.Those without evidence of progressive disease in the form of metastatic involvement were given thoracic irradiation starting on day 50, reaching a total dose of 60 Gy with 180 cGy daily fractions for 5 weeks and an accelerated boost of 150 cGy/fr delivered to the tumor area over the last two weeks. Paclitaxel was given concurrently during irradiation at 60 mg/m2 on days 50, 57, 64,71 and 78. The median age of the patient group was 51.5 years, (37–71). Nine patients (37.5%) had an ECOG PS of 0, while the remaining 15 had a PS of 1. The majority had squamous cell histology (n=13, 54.2%), and 9 patients had adenocarcinoma (37.5%).Results: After a median follow-up period of 9 (1–25) months, 13 patients experienced progression (54.2%), 5 of which progressed while on treatment and eight patients (33.3%) died. Two patients did not complete the planned treatment schedule; 1 patient had an anaphylactic reaction to paclitaxel infusion and the other withdrew consent. Overall response rate after completion of the protocol was 62.5% (2: complete response, 13: partial response). The most frequent side effect of concomitant chemoradiation was oesaphagitis, encountered in 16 patients. Grade 3–4 toxicity during both phases of treatment were: oesaphagitis in 4 patients (16.7%), mucositis in 1 (4.2%), anemia in 1 and neutropenia in 1 patient. Conclusions: This treatment protocol consisting of an induction combination followed by concomitant chemoradiation is a feasible regimen with a tolerable toxicity profile in patients with locally advanced NSCLC. No significant financial relationships to disclose.
Does pre-imatinib (IM) fluorescence in situ hybridization (FISH) predict myelosuppression and outcomes in chronic myeloid leukemia (CML)?
Authors: L. Lima, S. E. Assouline, D. Saxe, K. Mann, M. McLemore, L. Souza, M. Arellano, E. F. Winton, L. Bernal-Mizrachi, H. J. Khoury
Journal: Journal of Clinical Oncology (2009)

7071 Background: IM-associated myelosuppression occurs in 4–40% of CML patients (pts) vs. 1–16% in GIST. Selective inhibition of predominantly Philadelphia chromosome (Ph+) driven hematopoiesis may explain development of myelosuppression. In the absence of clinically applicable methods to quantitate Ph+/Ph- progenitor ratio, we hypothesized that the pre-IM percentage of BCR-ABL+ cells measured by FISH predicts myelosuppression. Methods: FISH pre-IM was available in 58 CML pts with chronic phase (CP, n=52), or advanced phase (AP, accelerated =3, blast =3) at 2 institutions. Grade &gt;3 myelosuppression occurred &lt; 60 days from starting IM in 9 pts (400 mg/d=6, &gt; 600 mg/d=3), leading to dose reduction (4), discontinuation (1) or continuation same dose IM despite myelosuppression (4). Cryopreserved marrow CD34+/CD38- cells from 14 pts with (7) or without (7) post-IM myelosuppression were sorted using flow cytometry and subjected to FISH analyses. Results: Median FISH was higher for myelosuppression (90%) vs. no myelosuppression (80%) pts (p= 0.03), and in AP vs. CP (97 % vs. 80%, p=0.003). Results of FISH on CD34+/CD38- cells will be reported. Table summarizes outcomes of CP pts. Median follow-up was 14 and 45 months for myelosuppression and no myelosuppression AP pts, respectively. Myelosuppression AP pts expired (CML=2, GVHD=1); 1 after complete hematologic (CHR) and minor cytogenetic response (CTGR), 1 after partial HR, and 1 resistant disease. All 3 pts without myelosuppression achieved CHR with major CTGR, and 2 had partial molecular response. 1 died from GVHD. Conclusions: Higher FISH pre-IM identifies a group of CML pts who develop myelosuppression and are less likely to respond to IM. [Table: see text] No significant financial relationships to disclose.
Tissue Patterning: Translating Design Principles from In Vivo to In Vitro
Authors: Alison P. McGuigan, Sahar Javaherian
Journal: Annual Review of Biomedical Engineering (2016)

Recapitulating the architecture of native tissue remains a significant challenge, impeding the progress of engineering tissues. Imposing appropriate organization is especially challenging in tissues that contain multiple cellular components in complex structural units. One solution is to mimic developmental processes in embryos. In an embryo, cells are organized by tissue patterning, whereby induction of fate-determining genes is spatially controlled to generate patterns of cell differentiation and maturation. Following patterning, the imposed cell organization is further reinforced by implementation of compartment boundaries, which prevent intermingling of cells from distinct phenotypic domains, thereby ensuring preservation of proper cell organization in growing and reorganizing tissues. Both morphogenic processes utilize a conserved set of fundamental principles, the implementation of which leads to highly regulated cell organization. In this article, we review these patterning principles in vivo and reflect on the progress made by tissue engineers in mimicking tissue patterning ex vivo.
Clinical Efficacy of Ivabradine in Patients With Inappropriate Sinus Tachycardia
Authors: Riccardo Cappato, Serenella Castelvecchio, Cristian Ricci, Elisabetta Bianco, Laura Vitali-Serdoz, Tomaso Gnecchi-Ruscone, Mario Pittalis, Luigi De Ambroggi, Mirko Baruscotti, Maddalena Gaeta, Francesco Furlanello, Dario Di Francesco, Pier Paolo Lupo
Journal: Journal of the American College of Cardiology (2012)
Gemcitabine plus cisplatin (GC): A salvage regimen for breast cancer patients who failed anthracycline and/or taxanes
Authors: I. Chitapanarux, V. Lorvidhaya, P. Kamnerdsupaphon, E. Tharavichitkul, H. Trakultivakorn, A. Somwangprasert, S. Sumitsawan
Journal: Journal of Clinical Oncology (2005)

757 Background: GC has demonstrated safety and efficacy in both heavily and minimally pretreated advanced breast cancer (BC) with response rate from 29%–63% (median 46%). All of studies had different schedule and dose of GC. We evaluated the activity and toxicity of another GC regimen in BC patients who failed chemotherapy with anthracycline and/or Taxanes as adjuvant or neoadjuvant or primary therapy. Methods: 30 BC patients who failed Anthracycline and/or Taxanes-based therapy, had measurable disease and a performance status 0–2 were recruited, of whom 29 were evaluable for response. Patients received Gemcitabine 1000 mg/m2 over 1-hour infusion on day 1 and 8 and Cisplatin 75 mg/m2 over 2-hour infusion on day 1 every 3 weeks up to 6 cycles or until disease progression or unacceptable toxicity. Results: After a median follow up of 6 month (range: 2–16). Of 30 patients, there were 29 female and 1 male, median age 45 years (24–65). 22 of patients (73%) were metastatic breast cancer, 6 (20%) were locally advanced breast cancer, 2 (7%) were locoregional recurrent. Prior treatment included up to 3 prior regimens: anthracyclines (27 patients), taxane (11 patients). A total of 106 cycles were administered (median 4 cycles per patients). Overall response rate was 51%, 1 achieved complete response (3%), 14 (48%) had partial response. There were 10 (35%) stable disease and 4 (14%) progression disease. The median time to disease progression was 8.1 months (2–10.8). The median time to response was 4 weeks (3–15). The median survival time was 11.8 months. Myelosuppresion was the most frequent side effect; grade 3/4 thrombocytopenia occurred in 17%, grade 3/4 neutropenia in 37%. Grade 3 Nausea-vomiting was found in 12% of cycles. There were no treatment related death. Treatment delays or omission due to hematotoxicity and renal toxicity in 7% and 6% of cycles. Conclusions: This schedule of GC proved clinical efficacy in salvage treatment in anthracycline and/or taxane pretreated breast cancer with manageable toxicity. No significant financial relationships to disclose.
Primary health care [letter]
Authors: Waterston T
Journal: BMJ (1984)

The essential features of primary health care and its value in a developing country are cogently described by Ms. Vivien Lees (9 June p. 1744.  This account of positive developments in health in Zimbabwe is a welcome counterbalance to adverse publicity the country has received since independence.  One aspect of primary health care touched on only briefly by Ms. Lees but which is crucial to its success is the participation of communities in its delivery.  This participation in Zimbabwe is mediated mainly through the selection of village or farm health workers by the communities whom they will serve.  Village health workers are intended to be responsible 1st to their community and only secondly to the medical hierarchy.  Their involvement in areas related to health such as education agriculture and politics may be as important as their health work.  Village health workers are expected to relate to their patients on a much more equal basis than professional health workers have done in the past.  Thus in the words of David Werner author of Where There is No Doctor they teach  by putting ideas into peoples heads but by drawing ideas out.  They may be more interested in social change than in behavioral change since health problems in many cases have social causes.  Ms. Lees rightly points out that some of the ideas of primary health care might be relevant to the United Kingdom.  It may be said that we already have acceptable accessible appropiate and affordable health care though one could argue about the last 2.  What we do not have is community participation in the sense of patients developing some degree of control over their own health.  This aspect of primary health care may be seen in UK to a limited extent in patient participation groups and in self help associations though these examples are still few and far between--and may be seen as a threat to the status quo if they start to become poltical which is the label often applied to any social action.  Perhaps this is an area where we can learn from the example of a developing country such as Zimbabwe.  (full text)
A randomized controlled trial of an educational program to improve accrual of older persons to cancer treatment protocols: CALGB 360001
Authors: G. Kimmick, A. Kornblith, J. Mandelblatt, B. Peterson, J. Johnson, J. Wheeler, H. Cohen, H. Muss
Journal: Journal of Clinical Oncology (2004)

8040 Background: Older persons (age 65 and older) are underrepresented in cancer clinical trials. CALGB 9670 (JCO 21:2268,2003) found that older women with breast cancer were as likely as younger women to participate in a clinical trial if offered but trials were offered to them less often. 42% of physicians stated that greater education about cancer treatment in older persons would improve accrual. Thus, we designed a randomized phase III trial of an educational program. Methods: Main member institutions and their affiliates with a mean accrual to treatment protocols of 5 or more patients per year over 3 years were randomized by main member institution to either: (1) standard information (n=72) or (2) educational intervention (n=53). Standard information included CALGB website access and periodic notification about existing CALGB trials. The geriatric educational intervention included standard information plus: 1) an educational seminar; 2) educational materials; 3) protocol checklists for use on charts; 4) monthly email and mail reminders for one year; and 5) a case discussion seminar. The main outcome was percent accrual of older persons to phase II and III treatment protocols during the 1st and 2nd years after study initiation compared to baseline accrual. Results: There were 6431 accruals during the study: 3032, 2160, and 1239 during baseline, year 1 and year 2, respectively. Percent accrual of older persons during the study is presented in the table. Conclusions: Decline in accrual is likely related to closure of several large accruing trials during the study. Lack of effect of the intervention may have been related to low intensity of the intervention. More intense and/or more far-reaching intervention is needed to improve accrual of older persons to clinical trials. Supported by CALGB (CA31946). Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen Amgen Network for Medical Communications
Safety and Efficacy Of Bendamustine In Patients With Aggressive Non-Hodgkin Lymphomas (NHL)
Authors: Jakob Hammersen, Michael Sommer, Christin Gössel, Ulf Teichgräber, Sabine Hahnfeld, Sebastian Scholl, Hans-Jörg Fricke, Ulrich Wedding, Eigendorff Ekkehard, Petersen Iver, Hartmut Merz, Andreas Hochhaus, Paul La Rosée
Journal: Blood (2013)
Brief Communication: Inhibition of Dimethylhydrazine-Induced Neoplasia of the Large Intestine by Disulfiram2
Authors: Lee W. Wattenberg
Journal: JNCI Journal of the National Cancer Institute (1975)

Journal Article Brief Communication: Inhibition of Dimethylhydrazine-Induced Neoplasia of the Large Intestine by Disulfiram Get access Lee W. Wattenberg Lee W. Wattenberg Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 54, Issue 4, April 1975, Pages 1005–1006, https://doi.org/10.1093/jnci/54.4.1005 Published: 01 April 1975 Article history Received: 25 October 1974 Accepted: 13 December 1974 Published: 01 April 1975
Predictive Impact of 2-<sup>18</sup>Fluoro-2-Deoxy-<scp>d</scp>-Glucose Positron Emission Tomography for Residual Postchemotherapy Masses in Patients With Bulky Seminoma
Authors: Maria De Santis, Carsten Bokemeyer, Alexander Becherer, Franz Stoiber, Karin Oechsle, Kurt Kletter, Bernhard M. Dohmen, Christian Dittrich, Jörg Pont
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To establish the predictive potential of 2- 18 fluoro-2-deoxy-d-glucose positron emission tomography (FDG PET) for detecting viable tumor tissue in residual postchemotherapy masses of seminoma patients. PATIENTS AND METHODS: In this prospective multicenter trial, results of FDG PET studies in seminoma patients with postchemotherapy masses ≥ 1 cm were correlated with either the histology of the resected lesion or the clinical outcome on follow-up without resection. Negative PET scans of residual lesions that were devoid of viable tumor tissue on resection or disappeared, shrunk, or remained stable in size for at least 2 years were rated as true-negative (TN). Positive scans without histologic or clinical evidence of tumor tissue were classified as false-positive. In patients with histologically positive or progressive lesions, positive PET scans were defined as true-positive (TP) and negative scans, false-negative (FN). RESULTS: Thirty-seven PET scans of 33 patients were assessable at a median follow-up time of 23 months (range, 2 to 46 months). Histologic data were available from nine patients who had undergone resection. Twenty-eight patients were followed-up clinically and radiologically. Twenty-eight scans were TN, eight were TP, and one was FN. All 14 residual lesions more than 3 cm and 22 (96%) of the 23 ≤ 3 cm were correctly predicted by FDG PET. The specificity (100%; 95% confidence interval [CI], 87.7% to 100%), sensitivity (89%; 95% CI, 51.7% to 99.7%), positive predictive value (100%), and the negative predictive value (97%) of FDG PET were superior to data obtained by assessing residual tumor size (≤ or &gt; 3 cm). CONCLUSION: FDG PET is a clinically useful predictor of viable tumor in postchemotherapy residuals of pure seminoma, especially those greater than 3 cm.
Phase I study of extended field intensity modulated radiation therapy (EF-IMRT) and docetaxel in patients with node-positive prostate cancer
Authors: R. J. Hauke, C. Enke
Journal: Journal of Clinical Oncology (2009)

e16154 Background: Treatment for patients with node positive prostate cancer remains challenging. With hormonal ablation therapy (HAT), conventional radiation doses to the lymph nodes produces few cures or long-term remissions, likely due to suboptimal doses and/or fields of radiation. Docetaxel has radiosensitizing properties. We conducted a phase I study combining HAT with EF-IMRT and concurrent docetaxel in men with biopsy-proven node positive prostate cancer. Methods: Eligible patients had biopsy proven N1M0 disease and adequate hematologic and hepatic function. All subjects received neoadjuvant HAT (bicalutamide 50 mg/d with an LHRH agonist) for at least 2 months but less than 13 months prior to EF-IMRT and continued for 2 years after completion of radiation (bicalutamide discontinued at the end of radiation). EF-IMRT target doses: prostate 81.0 Gy/45 fractions; intraprostatic target 81.0 - 84.6 Gy/45 fractions; pathologically involved lymph node 72 Gy/43 fractions; pelvic lymph nodes 54.0 Gy to 70.2 Gy/43 fractions. Ultrasound targeting and a water filled rectal catheter balloon were used daily to minimize movement and locate the prostate. Weekly docetaxel was administered during radiation at 5, 10 or 17 mg/m 2 . The primary endpoint was determining grade III/IV toxicity. Results: Nine patients have been treated. No grade III/IV toxicities occurred within the defined observation period. All subjects received their prescribed radiation and chemotherapy doses. One patient developed an anal fissure and one patient had tachyarrhythmias about 6 months after radiation. Seven of 9 patients are now beyond the 2 year post-radiation period; 4 patients remain in remission; one patient developed primary lung cancer; another was lost to follow up at 1 year post-radiation and 3 had relapsed disease within the 2 year post-radiation window. Conclusions: The addition of weekly docetaxel to EF-IMRT along with HAT is well tolerated in patients with node positive prostate cancer. Phase II studies are warranted based on these results. [Table: see text]
A limping child
Authors: David Lindsay, Sunil D’Souza
Journal: BMJ (2016)

A 15 month old girl was referred to the orthopaedics department by her general practitioner with an abnormal gait and a tendency to fall over more than her peers. There was no history of trauma or family history of note, and she was otherwise well.

She was born by uncomplicated spontaneous vaginal delivery at term and began walking independently aged 13 months. The midwife had commented to the mother during neonatal examination that the left hip was “a bit clicky,” but this had not been investigated further.

On examination she walked, apparently pain free, with a left sided lurch. Her left leg was 2 cm shorter than her right leg. Hip instability tests were normal. The general range of motion in the left hip was good, but abduction was limited and the telescope test was positive. A plain radiograph of the pelvis was obtained (fig 1⇓).





### 1. What is the diagnosis?

#### Short answer

Left sided developmental dysplasia of the hip.

#### Discussion

Developmental dysplasia of the hip (DDH) covers a spectrum of disorders, from mild dysplasia of the acetabulum without displacement to subluxation, dislocation, and aplasia of the joint.1 2 3 4 The incidence of true DDH is probably 1.3-5 per 1000 live births, but it depends on the definition used and the population studied, although evidence suggests that neonatal hip instability is found in 34-55 per 1000 live births.5 6 7 The features of DDH develop during the antenatal period and the early years of life and have been associated with several factors. Rarely, “teratological” hip dysplasia and dislocation occur in utero, but most children have only subtle signs …
Actin‐like 6A predicts poor prognosis of hepatocellular carcinoma and promotes metastasis and epithelial‐mesenchymal transition
Authors: Shuai Xiao, Rui‐Min Chang, Ming‐Yang Yang, Xiong Lei, Xiao Liu, Wen‐Bin Gao, Jing‐Lei Xiao, Lian‐Yue Yang
Journal: Hepatology (2015)

Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide because of metastasis. Epithelial‐mesenchymal transition (EMT) is widely considered to be crucial to the invasion‐metastasis cascade during cancer progression. Actin‐like 6A (ACTL6A) is initially verified important for cell proliferation, differentiation, and migration. In this study, we find that ACTL6A plays an essential role in metastasis and EMT of HCC. ACTL6A expression is up‐regulated in HCC cells and tissues. A high level of ACTL6A in HCCs is correlated with aggressive clinicopathological features and is an independent poor prognostic factor for overall and disease‐free survival of HCC patients. Ectopic expression of ACTL6A markedly promotes HCC cells migration, invasion, as well as EMT in vitro and promotes tumor growth and metastasis in the mouse xenograft model. Opposite results are observed when ACTL6A is knocked down. Mechanistically, ACTL6A promotes metastasis and EMT through activating Notch signaling. ACTL6A knockdown has the equal blockage effect as the Notch signaling inhibitor, N‐[N‐(3,5‐difluorophenacetyl)‐L‐alanyl]‐S‐phenylglycine t‐butylester, in HCC cells. Further studies indicate that ACTL6A might manipulate SRY (sex determining region Y)‐box 2 (SOX2) expression and then activate Notch1 signaling. Conclusions : ACTL6A promotes metastasis and EMT by SOX2/Notch1 signaling, indicating a prognostic biomarker candidate and a potential therapeutic target for HCC. (H epatology 2016;63:1256–1271)
Relationship of Specific IgM Responses with Infection and Lymphoproliferative Disease in Common Variable Immunodeficiency
Authors: Tukisa D. Smith, Paul J. Maglione, Charlotte Cunningham-Rundles
Journal: Journal of Allergy and Clinical Immunology (2016)

RATIONALE: Common Variable Immunodeficiency (CVID) is a complex primary immunodeficiency with the major feature of hypogammaglobulinemia.Patients with CVID usually do not have a genetic diagnosis, however up to 15% of patients with CVID have been found to have mutations of the gene TNFRSF13Bencoding TACI (transmembrane activator and calcium-modulator and cyclophilin-ligand interacter).Six mutations have been recognized thus far that are linked to a diagnosis of CVID.Here, we identify two additional mutations that are found in the TNFRSF13B gene encoding TACI in patients with CVID.METHODS: TNFRSF13B DNA Sequencing Test was performed by LabCorp and Correlagen Diagnostics on family members of two families with CVID.The coding sequence of TNFRSF13Bwas amplified by PCR, and each PCR product then sequenced bi-directionally using the Sanger sequencing methodology.RESULTS: We investigated two families with CVID and identified the c.81G>A TNFRSF13B homozygous mutation in two siblings of Family A and the father and two children of Family B. There was an additional c.674a>G heterozygous mutation identified in Family A. Neither of these mutations have been previously identified to be associated with CVID, they were both labeled having as unclear significance for CVID thus the test was inconclusive.CONCLUSIONS: We believe that in addition to the six already recognized mutations in TACI that are linked to CVID, the c.81G>A TNFRSF13B homozygous mutation and the TNFRSF13B c.674a>G heterozygous mutation are linked to CVID as well.