tbuckley/cabot-search huggingface dataset:
Dyspnea in oncologic patients as an important cause of attendance in emergency room
Authors: S. Serrano, M. Tobeña, M. Vidal, A. Ferrer, E. Millastre, M. Ruiz Echarri, I. Pajares, D. Lopez, A. Tres, J. Lambea
Journal: Journal of Clinical Oncology (2009)

e20705 Background: Attending oncologic patients in emergency room because of a large variety of symptoms due to treatments or tumor complications is very common. Our objective is to estimate the prevalence of dyspnea in oncologic patients and its etiology. Methods: From October 2007 to October 2008 we recollected 560 oncologic patients who were seen on Emergency room. It was revised cause of consultation, tumors´ location and stage, active or palliative care, diagnosis and treatment. Results: 71 of the 560 patients (12.7%) related dyspnea as cause of consultation, being the third cause of attendance in Emergency room after pain (126 patients, 22.5%) and fever (98 patients, 17.5%). The most common tumor´s location was lung in 38 of the 71 patients (53.52%), followed by colorectal cancer (11.3%) and breast (9.9%). 76.8% were advanced oncologic patients (stage IV). Diagnosis was respiratory infection in 19 patients (26.8 %) followed by malignant pleural bleeding (10 patients, 14.1%), disease progression (9 patients, 12.7%) and pulmonary embolism (5 patients, 7%). Dyspnea was a multifactorial symptom in 21 of the 71 patients (29.6%) without an etiological diagnosis. In 47 patients (66.2%) was required admission with a mortal evolution in more than 50%. Conclusions: In oncologic patients dyspnea is a frequent cause of consultation in Emergency room with high rates of morbility and mortality. It affects to patients´quality of life. When etiology is diagnosed the most common is respiratory infection. We should make an effort to offer the best supportive care. No significant financial relationships to disclose.
Neoadjuvant cisplatin/gemcitabine chemotherapy for muscle invasive bladder carcinoma: A single institution experience.
Authors: Roshni Deepa Kalachand, Felicity McDonnell, Deaglan McHugh, Raymond McDermott
Journal: Journal of Clinical Oncology (2012)

e15016 Background: Neoadjuvant chemotherapy (NAC) with MVAC has been shown to improve overall survival in patients with muscle invasive transitional cell carcinoma of the bladder (MIBC), with pathological complete response (pCR) correlating with a survival benefit. Despite the lack of randomized data for cisplatin/gemcitabine (GC) in the neoadjuvant setting, it is commonly used in clinical practice, given its favorable toxicity profile and comparable efficacy to MVAC in the context of metastatic disease. Methods: Data was retrospectively obtained on 93 patients with T2-T4, N0-2 M0 MIBC treated with curative intent in our institution between 2005-2011. Characteristics of patients treated with GC NAC, along with treatment tolerance and outcomes, were collected. Results: Of 93 patients, 27% (n=25) were treated with GC NAC. Median age was 66 (range 49-81). 88% (n=22) of patients were clinical stage T3/4 and/or N1/2. 68% of patients received 28-day cycles of GC, with 32% receiving 21-day cycles of GC. One patient had split cisplatin dosing. 91% and 82% of planned cisplatin and gemcitabine were delivered, respectively. There were no treatment-related deaths. On completion of NAC, 52% (n=13) of patients underwent radical cystectomy, of whom 38% (n=5) achieved a pCR, and 62% (n=8) were downstaged to non-muscle invasive bladder cancer (nMIBC). Definitive chemoradiotherapy was used in 20% (n=5) of patients, whilst 12% (n=3) had no radical treatment due to progressive disease (n=2), or to a decline in ECOG performance status (n=1). Amongst patients without radical cystectomy, 12% (n=3) of patients achieved a biopsy-proven clinical complete response (cCR). In the intent-to-treat population, median disease-free survival was 32 months, and median overall survival 38.8 months. All patients with a pCR, cCR, or downstaging to nMIBC (n=12), were alive at a median follow-up of 16 months (3.9 – 49.1 months), although 1 patient had relapsed. Conclusions: GC is a well-tolerated regimen in the neoadjuvant treatment of MIBC, with a pCR rate comparable to that reported with MVAC. Our findings support the use of GC in the neoadjuvant treatment of MIBC.
Effect of familial breast cancer outcomes on health behaviors of relatives
Authors: S. G. Fisher, P. Mumby, S. Kohli
Journal: Journal of Clinical Oncology (2007)

1521 Background: While the disease outcomes of breast cancer probands do not affect the objective risk of first degree relatives (FDR), the morbidity and mortality experience may impact their subsequent perceptions and health behaviors. This study examines the influence of a proband’s disease course on screening behaviors, perceived risk, self-efficacy, traumatic stress and related mood disturbances of FDR. Methods: A cross-sectional sample of 149 FDR was recruited (79% of respondents) by invitations distributed by 545 probands. Respondents were categorized into a ‘high impact’ group whose familial proband had expired, relapsed or undergone intensive chemotherapy (n=55), and a ‘low impact’ group whose proband was disease-free after surgery ± radiation (n=94). This sample provided a power of 84% for detection of a 1.5 unit difference in screening indices and a 10% difference in perceived risk between groups with a two-sided alpha level of 0.05. Parameters were measured by self-administered, mailed surveys of newly-developed and established instruments. Objective risk assessments were completed by a genetic counselor. Statistical analyses included parametric and non-parametric methods, as appropriate. Results: While the high impact group reported perceptions of greater familial proband suffering (8.6 vs.5.8) and greater anxiety and doubt regarding mammography benefits (11% vs. 1%) (p&lt;0.01), there was no statistically significant difference between groups in screening behaviors or perceived risk. The high impact group experienced sleep disturbances (28%), emotional stress (52%), and mood swings (61%) more often than the comparison group (p&lt;0.001). FDR with the highest objective risk had significantly higher scores on screening indices and perceived risk (p&lt;0.01) but significantly lower knowledge regarding breast cancer (p=0.04). Conclusions: This study suggests that while morbidity and mortality of familial probands is not associated with screening practices of FDR, it does have a negative impact on their psychological well-being. Enhanced strategies to educate and support FDR regarding familial breast cancer risk and potential psychological repercussions of the proband’s experience are warranted. No significant financial relationships to disclose.
Metabolic Reprogramming of Myeloid Cells in Response to Factors of "Emergency" Myelopoiesis By Myeloid-Specific PD-1 Ablation, Regulates Myeloid Lineage Fate Commitment and Anti-Tumor Immunity
Authors: Laura Strauss, Jessica D Weaver, Rinku Pal, John Asara, Nikolaos Patsoukis, Vassiliki A Boussiotis
Journal: Blood (2018)
A novel tumor suppressor protein encoded by circular AKT3 RNA inhibits glioblastoma tumorigenicity by competing with active phosphoinositide-dependent Kinase-1
Authors: Xin Xia, Xixi Li, Fanying Li, Xujia Wu, Maolei Zhang, Huangkai Zhou, Nunu Huang, Xuesong Yang, Feizhe Xiao, Dawei Liu, Lixuan Yang, Nu Zhang
Journal: Molecular Cancer (2019)

Abstract Background The RTK/PI3K/AKT pathway plays key roles in the development and progression of many cancers, including GBM. As a regulatory molecule and a potential drug target, the oncogenic role of AKT has been substantially studied. Three isoforms of AKT have been identified, including AKT1, AKT2 and AKT3, but their individual functions in GBM remain controversial. Moreover, it is not known if there are more AKT alternative splicing variants. Methods High-throughput RNA sequencing and quantitative reverse transcription-PCR were used to identify the differentially expressed circRNAs in GBM samples and in paired normal tissues. High throughput RNA sequencing was used to identify circ-AKT3 regulated signaling pathways. Mass spectrometry, western blotting and immunofluorescence staining analyses were used to validate AKT3-174aa expression. The tumor suppressive role of AKT3-174aa was validated in vitro and in vivo. The competing interaction between AKT3-174aa and p-PDK1 was investigated by mass spectrometry and immunoprecipitation analyses. Results Circ-AKT3 is a previously uncharacterized AKT transcript variant. Circ-AKT3 is expressed at low levels in GBM tissues compared with the expression in paired adjacent normal brain tissues. Circ-AKT3 encodes a 174 amino acid (aa) novel protein, which we named AKT3-174aa, by utilizing overlapping start-stop codons. AKT3-174aa overexpression decreased the cell proliferation, radiation resistance and in vivo tumorigenicity of GBM cells, while the knockdown of circ-AKT3 enhanced the malignant phenotypes of astrocytoma cells. AKT3-174aa competitively interacts with phosphorylated PDK1, reduces AKT-thr308 phosphorylation, and plays a negative regulatory role in modulating the PI3K/AKT signal intensity. Conclusions Our data indicate that the impaired circRNA expression of the AKT3 gene contributes to GBM tumorigenesis, and our data corroborate the hypothesis that restoring AKT3-174aa while inhibiting activated AKT may provide more benefits for certain GBM patients.
Breast Cancer Index and prediction of benefit from extended endocrine therapy in breast cancer patients treated in the Adjuvant Tamoxifen—To Offer More? (aTTom) trial
Authors: J.M.S. Bartlett, D.C. Sgroi, K. Treuner, Y. Zhang, I. Ahmed, T. Piper, R. Salunga, E.F. Brachtel, S.J. Pirrie, C.A. Schnabel, D.W. Rea
Journal: Annals of Oncology (2019)

BackgroundExtending the duration of adjuvant endocrine therapy reduces the risk of recurrence in a subset of women with early-stage hormone receptor-positive (HR+) breast cancer. Validated predictive biomarkers of endocrine response could significantly improve patient selection for extended therapy. Breast cancer index (BCI) [HOXB13/IL17BR ratio (H/I)] was evaluated for its ability to predict benefit from extended endocrine therapy in patients previously randomized in the Adjuvant Tamoxifen—To Offer More? (aTTom) trial.Patients and methodsTrans-aTTom is a multi-institutional, prospective–retrospective study in patients with available formalin-fixed paraffin-embedded primary tumor blocks. BCI testing and central determination of estrogen receptor (ER) and progesterone receptor (PR) status by immunohistochemistry were carried out blinded to clinical outcome. Survival endpoints were evaluated using Kaplan–Meier analysis and Cox regression with recurrence-free interval (RFI) as the primary endpoint. Interaction between extended endocrine therapy and BCI (H/I) was assessed using the likelihood ratio test.ResultsOf 583 HR+, N+ patients analyzed, 49% classified as BCI (H/I)-High derived a significant benefit from 10 versus 5 years of tamoxifen treatment [hazard ratio (HR): 0.35; 95% confidence interval (CI) 0.15–0.86; 10.2% absolute risk reduction based on RFI, P = 0.027]. BCI (H/I)-low patients showed no significant benefit from extended endocrine therapy (HR: 1.07; 95% CI 0.69–1.65; −0.2% absolute risk reduction; P = 0.768). Continuous BCI (H/I) levels predicted the magnitude of benefit from extended tamoxifen, whereas centralized ER and PR did not. Interaction between extended tamoxifen treatment and BCI (H/I) was statistically significant (P = 0.012), adjusting for clinicopathological factors.ConclusionBCI by high H/I expression was predictive of endocrine response and identified a subset of HR+, N+ patients with significant benefit from 10 versus 5 years of tamoxifen therapy. These data provide further validation, consistent with previous MA.17 data, establishing level 1B evidence for BCI as a predictive biomarker of benefit from extended endocrine therapy.Trial registrationISRCTN17222211; NCT00003678.
Expression of prostate-specific membrane antigen (PSMA) in the neovasculature of nonprostate human tumors of epithelial and nonepithelial origin.
Authors: Wells Wrisley Magargal, Dapeng Qian, William C. Olson
Journal: Journal of Clinical Oncology (2012)

e21131 Background: PSMA is a transmembrane glycoprotein present not only in prostate cancer epithelial cells but also in the neovasculature of many other solid tumors. This expression profile makes it an attractive target for tumor-specific delivery of chemotherapeutic agents to the neovasculature of non-prostate solid tumors. We generated an antibody-drug conjugate (ADC) comprised of a fully human anti-PSMA monoclonal antibody (mAb), conjugated to monomethylauristatin E, a potent cytotoxic agent. PSMA ADC is currently undergoing Phase I clinical testing in men with advanced prostate cancer. Previously, we reported high level PSMA expression in the neovasculature of carcinomas from kidney, colon, non-small cell lung, breast and liver. Here we extend our study to additional carcinomas as well as tumors of non-epithelial origin. Methods: Expression of PSMA protein was evaluated by immunohistochemical analysis of frozen tissues using biotinylated mAb that specifically recognizes the native dimeric form of PSMA. The semi-quantitative scheme of 0 to 3+ was used to indicate the amount of epitope based on the intensity of the color reaction. The strongest possible staining was scored 3+ while 2+ staining was considered moderate and 1+ was considered weak. Endothelial cells were detected by morphology and staining of selected slides with an anti-CD 34 mAb. Results: Moderate to strong (2+ to 3+) neovasculature staining was seen in over 80% of specimens from, bladder (10/10), ovarian (9/10) and pancreatic (8/10) carcinomas. Moderate to strong neovascular staining was seen in 40-80% of specimens from several non-carcinoma tumors, including glioblastoma (4/5), melanoma (7/10), non-Hodgkins lymphoma (6/10), osteosarcoma (3/7) and myeloma (2/5). Only weak (1+) staining was seen in angiosarcoma (2/3) and no staining was observed in the testicular cancers tested (0/5). Conclusions: Robust neovascular expression of PSMA dimer was observed across all eight non-prostatic carcinomas. Significant neovascular expression was also observed in several non-epithelial tumors. These findings may be relevant to the development of novel anti-neovascular therapies that target PSMA.
Innovation, education, and research: A multidisciplinary survivorship care model.
Authors: Hira Latif, Patrick Martone, James Edward Shaw, Eric Wisotzky, Asma Ali Dilawari
Journal: Journal of Clinical Oncology (2019)

10519 Background: Advances in early detection, therapeutics, and an aging population are expected to lead to an increase in the number of cancer survivors in the United States to 20 million by year 2026. The Institute of Medicine and Commission on Cancer recommends delivery of survivorship care plans on completion of curative treatment. While models exist for high-quality survivorship care, institutions encounter barriers such as lack of resources and limited training in survivorship. Our institution piloted a unique model combining fellows’ education with guideline-driven recommendations from a multidisciplinary team to provide consolidated survivorship care. Methods: A survey for self-reported competence and experience was conducted amongst the hematology and oncology fellows at the MedStar Washington Hospital Center. A bimonthly clinic staffed by a medical oncologist, oncology fellow and a cancer rehabilitation fellow was initiated in September 2018. Didactic lectures, curriculum syllabus and recommended assessments were established. Screening tools for distress, patients’ confidence in knowledge about survivorship and physical function via PROMIS 20a were administered; clinical assessments including the “6-minute walk test” were used to assess cardiovascular health. Results: Most fellows had not encountered a survivor of lung (16%), GU (0%) and head and neck cancer (33%). Majority of the fellows had never delivered a survivorship care plan. Scores were low in competence and experience in survivorship. By December 2018, 15 patients with 17 diagnoses of cancer were referred to the clinic. 10 were survivors of hematologic malignancies while 7 were of solid tumors. The no-show rate was 40%. Fellows conducted the assessments and were supervised by an oncology attending. Of the 9 patients seen, 4 were referred for physical therapy; additional referrals for psychology and cardiology were frequent. Conclusions: A comprehensive multidisciplinary survivorship clinic focusing on fellows’ education is a feasible model for delivery of survivorship care and aims to bridge the gap in experience and competence of fellows. Future goals include re-assessment of patient-reported outcomes, physical function, and competence of fellows.
Doctors warned to be vigilant after cases of antibiotic resistant meningitis in people returning from Mecca
Authors: Susan Mayor
Journal: BMJ (2019)

Doctors should ask patients with symptoms that could be due to meningococcal infection about recent travel, Public Health England has warned after three cases of ciprofloxacin resistant meningococcal infection have been associated with recent travel to Mecca, Saudi Arabia.1

“The identification of resistant meningococcal conjunctivitis in people returning from Mecca highlights the urgent need to review currently recommended prophylactic measures for Hajj pilgrims, how best to prevent spread of N meningitidis between people attending mass gatherings, and how to protect contacts on return,” said Alimuddin Zumla, from University …
Economic value of zoledronic acid compared with placebo in the treatment of skeletal metastases in patients with solid tumors: The case of the United Kingdom (UK)
Authors: A. A. Marfatia, M. F. Botteman, I. Foley, J. Brandman, C. J. Langer
Journal: Journal of Clinical Oncology (2007)

6603 Background: Zoledronic acid (ZA) reduces the risk of skeletal-related events (SREs) in patients with solid tumors (i.e., renal cell carcinoma, thyroid, head and neck, small cell lung, or others cancers, excluding breast, prostate and non small cell lung [NSCLC] cancers) and bone metastases. This analysis assessed, from the perspective of the UK National Health Service, the economic impact of ZA in this patient population. Methods: A literature-based decision-analytic model was developed to compare the direct costs and quality adjusted life years (QALY) of patients with bone metastases secondary to solid tumors receiving ZA or placebo. Survival, SRE incidence, and number of infusions administered were obtained from a clinical trial comparing patients randomized to 4 mg ZA or placebo for up to 21 months. Drug acquisition and administration costs and SRE costs were estimated using published sources and national fee schedules (e.g., NHS reference costs, British National Formulary). The impact of SREs on quality of life was estimated using the literature. Consistent with previous economic analyses of bisphosphonates in cancers (e.g., Hillner et al, 2000), patients were assumed to experience quality of life improvements lasting 1 month for each SRE avoided. Results: The average remaining life expectancy was conservatively assumed equal in both groups and was 9.54 months (median, 6.61 months). Patients receiving placebo were projected to experience 2.64 SREs on average v. 1.64 SREs among ZA patients. QALYs were estimated at 0.3917 per patient (pp) and 0.3728 pp in the ZA and placebo groups, respectively. ZA drug- related costs were estimated at £1,386 pp, based on an average of 5.52 infusions pp. The use of ZA was associated with a reduction of £1,830 pp in SRE costs. Overall, ZA saved costs and increased QALYs v. no therapy, by £445 pp and 0.0189 QALYs pp, respectively. In sensitivity analyses, ZA cost £25,000 or less per QALY under a wide range of assumptions. Conclusions: The use of ZA leads to fewer SREs, better estimated quality of life, and lower costs relative to placebo in UK patients with bone metastases secondary to solid tumors other than breast, prostate or NSCLC cancer. ZA appears therefore highly cost effective in this population. No significant financial relationships to disclose.
Treatment with combination of all-trans retinoic acid and interferon-gamma regressed human glioblastoma T98G xenografts in nude mice
Authors: Surajit Karmakar, Thomas Walle, Naren Banik, Swapan Ray
Journal: Cancer Research (2008)

4035  Glioblastoma is the most malignant and prevalent human brain tumor of astroglial origin. It is considered as the death sentence in patients due to its poor response or resistance to existing therapeutic agents. Therefore, the search continues for an effective therapy for controlling the growth of this devastating cancer. This investigation used all-trans retinoic acid (ATRA) and interferon-gamma (IFN-γ) alone and in combination for controlling the growth of human glioblastoma T98G xenografted in nude mice. For development of xenografts, 6-week old nude mice (about 20 g each) were subcutaneously injected with a (1:1) mixture of exponentially growing T98G cells (6 million cells/mouse) and Matrigel. The mice were allowed to develop the tumors. Animals with the 3-week old xenografts were randomly assigned to four different groups: control, ATRA, IFN-γ, and ATRA plus IFN-γ. Control animals did not receive any therapy. Other animals with xenografts received a daily dose of ATRA (1.5 µg/kg), IFN-γ (5000 units/kg), or ATRA (1.5 µg/kg) plus 4 h later IFN-γ (5000 units/kg) for 7 days. Histopathological examination showed characteristic growth of glioblastoma in control group, inhibition of tumor cell proliferation and astrocytic differentiation in ATRA group, induction of modest amount of apoptosis in IFN-γ group, and occurrence of differentiation and enhancement of apoptosis in ATRA plus IFN-γ group. Western blot analyses showed that ATRA plus IFN-γ treatment activated extrinsic pathway of apoptosis by activation of caspase-8 and cleavage of Bid to tBid and also down regulated anti-apoptotic hTERT, c-IAP2 and survivin, favoring the process of apoptosis. Western blotting showed activation of cysteine protease calpain and involvement of both mitochondrial caspase-independent pathway by robust release of AIF and caspase-dependent pathway by the activation of caspase-9 and caspase-3 in T98G xenografts for apoptosis following combination therapy with ATRA plus IFN-γ. Increased activities of calpain and caspase-3 degraded 270 kD α-spectrin at the specific sites to generate 145 kD spectrin breakdown product (SBDP) and 120 kD SBDP, respectively. Further, increased activity of caspase-3 cleaved inhibitor-of-caspase-activated DNase (ICAD) and release CAD for DNA fragmentation for apoptosis in tumors treated with the combination of ATRA and IFN-γ. In situ TUNEL and double immunofluorescent labelings detected apoptosis with increased expression of calpain, caspase-12, and caspase-3 in tumors treated with IFN-γ, or ATRA plus IFN-γ. Thus, we developed a combination therapy for increasing apoptosis in human glioblastoma in vivo. This investigation was supported in part by the R01 grants (CA-91460 and NS-57811).