tbuckley/cabot-search huggingface dataset:
Quality of life (QOL) of older adults with acute myeloid leukemia (AML): Effects of treatment and time
Authors: M. Leach, M. Kowgier, H. Kermalli, A. Schattner, V. Gupta, M. Minden, G. A. Tomlinson, S. M. Alibhai
Journal: Journal of Clinical Oncology (2006)

6566 Background: AML in older adults has a poor prognosis. Although intensive chemotherapy may be associated with a modest improvement in survival, this needs to be balanced against possible worsening of QOL. However, published research in this area is limited. Methods: English-speaking patients aged 60 or older presenting with newly diagnosed AML to our referral centre were enrolled. Patients were excluded if life expectancy was &lt;1 month. QOL was measured at baseline and at 1, 4, and 6 months. Questionnaires included the European Organization for the Research and Treatment of Cancer QLQ-C30 (global health and 5 QOL domains) and the Functional Assessment of Cancer Therapy Fatigue subscale. Patients were stratified into intensive (IT) and non-intensive treatment (NIT) groups. Baseline scores between groups were compared using Student’s T-test. Repeated measures modeling was used to compare the groups over time. Results: From June 2003 to December 2005, 63 patients (mean age 72, 46 IT, 17 NIT) were enrolled. At baseline, physical function and social function were the most affected domains and most patients had moderate fatigue. IT patients had better physical function and slightly less fatigue at baseline than NIT patients but were similar in 4 QOL domains and global health scores. By 6 months, 44% of IT and 60% of NIT patients had died. Over time, global health, role function, and emotional function improved but physical function, social function, and cognitive function did not change. Improvements in QOL domains were similar for IT and NIT patients for all measures. Fatigue scores remained unchanged over time. Conclusion: Intensive chemotherapy is not associated with worse QOL than NIT in older patients with AML, although our small sample size and attrition bias may overestimate QOL among survivors. Concerns about worse QOL with IT appear to be unfounded and this should not deter clinicians from considering IT for older adults with AML. No significant financial relationships to disclose.
Molecular cloning and characterization of the human HLJ1 gene promoter
Authors: Chi-Chung Wang, Jeremy J. W. Chen, Pan-Chyr Yang
Journal: Cancer Research (2004)

947   A common treatment of malignant glioma, in addition to radiotherapy, is the administration of BCNU as a chemotherapeutic drug. The delivery of BCNU to the cells is essential and depends on the functional blood volume of the tumor. The aim of this study was to quantify the functional blood volume and the mean vessel size of a heterogeneously (C6) and homogeneously perfused (GV1A1) glioma model using MRI. MRI results were related to the chemo sensitivity of the tumors. The anti-tumor activity of the BCNU was evaluated in a panel of glioma models. Two syngeneic rat glioma models (C6 and GV1A1) were chosen according to their different response to BCNU treatment. C6 or GV1A1 glioma cells were orthotopically injected in the caudate putamen of rats. Tumors established after 3-10 days, at this time, rats were randomised to receive an IV bolus of 13-15 mg/kg BCNU. The median survival time of non treated GV1A1-bearing rats was 16 days whereas the median survival time of the C6-bearing rats was 25 days. Blood volume (BV) and vessel size imaging (VSI) were performed at 2.35T. The tumors were imaged 4 days before the median survival time. The MRI protocol started with a diffusion-weighted SE acquisition, followed by a pre-contrast acquisition of a multi slice and multiple gradient echoes - spin echo images. The measurement was repeated 4 min after injection of an intravascular contrast agent (Sinerem). VSI maps were computed using the ΔR2* and ΔR2 maps. CBV maps are proportional to ΔR2* maps. The mean VSI and mean BV were calculated for all non necrotic tumor voxels. During growth of the C6 glioma, the central regions of the tumor became necrotic, whereas the GV1A1 glioma showed a homogeneous distribution of the blood volume in all tumor slices at different growth stages. This was confirmed by a homogeneous uptake of GdDOTA. The mean functional blood volume was decreased and the mean VSI was increased for both glioma models in comparison to the cortex and striatum in the contralateral hemisphere. The mean VSI value in C6 glioma in non-necrotic regions at D24 was 20 ± 6 μm (cortex and striatum 4 ± 1 μm) and the decrease of the mean BV value was approximately 50%. In the GV1A1 glioma (n = 6), the mean VSI value was 6 ± 3 μm at D12 and the decrease of the mean BV value was 40 % in comparison to the contralateral cortex and striatum. After administration of BCNU, the increase live span (ILS) is 42 % for the C6 glioma and 74 % for the GV1A1 glioma. We therefore conclude that MR imaging is a useful technology to demonstrate changes in tumor vascular status compared with adjacent normal tissues. The spatial distribution of functional and permeable microvessels, rather than changes in the blood volume, may have a prognostic value in these 2 glioma models for BCNU treatment.
Epidemiologic and Age-Dependent Data on Multiple Myeloma in Austria&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;, &lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;
Authors: H Ludwig, E Fritz, H P Friedl
Journal: JNCI Journal of the National Cancer Institute (1982)

The mortality rates for multiple myeloma showed an increasing trend between 1969 and 1979, when multiple myeloma accounted for 6%0 of the reported cancer deaths in Austria. The median age at diagnosis was relatively high: 68.5 years for males and 69.0 years for females. The age-corrected male:female ratio of 1.23:1 indicated a higher incidence of multiple myeloma in males. Age-standardized (standard population for Europe) incidence rates amounted to 1.5/100,000 male inhabitants and 1.2/100,000 female inhabitants/year. In a subsample of patients with multiple myeloma, the paraprotein types as well as the κ:λ ratio resembled the frequency distribution of normal immunoglobulins. There were no age-related differences for the stages of the disease and the poor risk factors at diagnosis for patients 65 years old or younger or for those over 65 years of age at diagnosis. Survival rates were significantly higher for younger patients than for older ones, with a 50% survival time of 45 and 26 months, respectively. The differences resulted solely from the dissimilar general life expectancies in both groups, and survival rates with strict regard to multiple myeloma proved to be identical in younger and older patients.
Higher cough flow is associated with lower risk of pneumonia in acute stroke
Authors: Stefan T Kulnik, Surinder S Birring, John Hodsoll, John Moxham, Gerrard F Rafferty, Lalit Kalra
Journal: Thorax (2016)

There is little available evidence to demonstrate how cough strength mediates the risk of aspiration-related pneumonia in acute stroke. Our secondary analysis of trial data indicates that risk of pneumonia reduces with increasing peak cough flow (PCF) of voluntary cough (OR 0.994 for each 1 L/min increase in PCF, 95% CI 0.988 to 1.0, p=0.035); and to a lesser degree with increasing PCF of reflex cough (OR 0.998 for each 1 L/min increase in PCF, 95% CI 0.992 to 1.004, p=0.475). These data serve hypothesis generation. Further studies are needed to confirm these findings and validate their clinical utility.ISRCTN40298220 (post-results).
Prospective analysis of endocrine function in children with residual/recurrent low-grade brain tumours treated with high-precision stereotactic conformal radiotherapy
Authors: D. Dutta, N. Shah, T. Gupta, A. Munshi, R. Jalali
Journal: Journal of Clinical Oncology (2008)

2049 Background: We report prospective neuroendocrine function in children and young adults with residual/recurrent low-grade brain tumours treated with high-precision stereotactic conformal radiotherapy (SCRT). Methods: 57 patients (median 13 yrs, range 5- 25 yrs; 42 male, 15 females) with low-grade brain tumours treated with SCRT comprise the present patient population. The histologic types included 18 craniopharyngioma, 16 optic chiasmatic glioma, 12 cerebral gliomas and 6 patients with cerebellar astrocytoma. Patients had undergone surgical procedure including biopsy in 19 and partial excision in 38 patients. Results: At a median follow-up of 27.5 months, 51 patients have controlled disease. Four patients have died of disease progression and 1 patient is alive with progression yielding 2 and 3 year overall survival of 90% and 85% respectively. Before starting radiotherapy, 30 out of 57 patients (53%) had hormone deficiency in at least one axis requiring replacement. This implies that factors other than radiotherapy such as tumour and surgery may also be responsible. Hormone dysfunction was significantly more in sellar tumour (27 of 38 patients, 71%; p=0.006) and tumours close to PHA (0.001). At baseline, hormone dysfunction was seen significantly more in GH axis (27 patients, 48%), corticosteroid axis (23 patients, 40%) than thyroid axis (10 patients, 17.5%) and sex hormone axes (1 patient, 2%). At 2- and 3-year follow-ups, hormone deficiency in at least 1 axis was seen in 14/29 patients (48%) and 11/22 patients (50%) respectively. At 2-year follow-up, three patients developed additional deficiency (1 each in thyroid, steroid and sex-hormone axis). At 3-year follow-up, only 1 more patient (14%) developed additional deficiency. Conclusions: More than half of patients with low-grade brain tumours before radiotherapy had hormone deficiency in at least one axis, with maximum deficiency seen in sellar tumours. Hormone dysfunction was seen in a very small number of patients at 2- and 3-year follow-ups in this cohort of patients treated with SCRT. Validation of these encouraging results will come from maturation of data in a larger number of patients at a longer follow-up. No significant financial relationships to disclose.
Interactive Effects of Physical Fitness and Body Mass Index on the Risk of Hypertension
Authors: Casey Crump, Jan Sundquist, Marilyn A. Winkleby, Kristina Sundquist
Journal: JAMA Internal Medicine (2016)

<h3>Importance</h3> High body mass index (BMI) and low physical fitness are risk factors for hypertension, but their interactive effects are unknown. Elucidation of interactions between these modifiable risk factors may help inform more effective interventions in susceptible subgroups. <h3>Objective</h3> To determine the interactive effects of BMI and physical fitness on the risk of hypertension in a large national cohort. <h3>Design, Setting, and Participants</h3> This cohort study included all 1 547 189 military conscripts in Sweden from January 1, 1969, through December 31, 1997 (97%-98% of all 18-year-old men nationwide each year), who were followed up through December 31, 2012 (maximum age, 62 years). Data analysis was conducted August 1 through August 15, 2015. <h3>Exposures</h3> Standardized aerobic capacity, muscular strength, and BMI measurements obtained at a military conscription examination. <h3>Main Outcomes and Measures</h3> Hypertension identified from outpatient and inpatient diagnoses. <h3>Results</h3> A total of 93 035 men (6.0%) were diagnosed with hypertension in 39.7 million person-years of follow-up. High BMI and low aerobic capacity (but not muscular strength) were associated with increased risk of hypertension, independent of family history and socioeconomic factors (BMI, overweight or obese vs normal: incidence rate ratio, 2.51; 95% CI, 2.46-2.55;<i>P</i> &lt; .001; aerobic capacity, lowest vs highest tertile: incidence rate ratio, 1.50; 95% CI, 1.47-1.54;<i>P</i> &lt; .001). Aerobic capacity was inversely associated with hypertension across its full distribution (incidence rate ratio per 100 W, 0.70; 95% CI, 0.69-0.71;<i>P</i> &lt; .001). A combination of high BMI (overweight or obese vs normal) and low aerobic capacity (lowest vs highest tertile) was associated with the highest risk of hypertension (incidence rate ratio, 3.53; 95% CI, 3.41-3.66;<i>P</i> &lt; .001) and had a negative additive and multiplicative interaction (<i>P</i> &lt; .001). Although high BMI was a significant risk factor for hypertension, low aerobic capacity also was a significant risk factor among those with normal BMI. <h3>Conclusions and Relevance</h3> In this large national cohort study, high BMI and low aerobic capacity in late adolescence were associated with higher risk of hypertension in adulthood. If confirmed, our findings suggest that interventions to prevent hypertension should begin early in life and include not only weight control but aerobic fitness, even among persons with normal BMI.
Case studies of patients receiving intraventricular topotecan for treatment of neoplastic meningitis.
Authors: J. G. Walker, D. L. Schultz, K. A. Grisdale, M. D. Groves
Journal: Journal of Clinical Oncology (2010)

e12540 Background: As cancer patients experience longer survival times, the leptomeningies increasingly play host to metastatic disease from a variety of primary sources. The disease is known as lymphomatous meningitis, or carcinomatous meningitis, depending on the site of origin of the tumor. Generically, the disease can be called neoplastic meningitis (NM) or leptomeningeal metastasis. Sadly, NM frequently results in neurological and functional devastation in afflicted patients. Research into effective and well tolerated treatments is on the rise as the incidence of NM increases. Intrathecal and intraventricular (IVt) chemotherapy via an implanted ventricular reservoir is often administered in order to circumvent the blood-brain-barrier and blood-CSF-barrier, and to provide direct contact of drug with tumor cells. The use of IVt topotecan in the treatment of NM results in progression-free survival outcomes similar to other IVt chemotherapies, while being particularly well tolerated by most patients. Methods: We present case studies from 5 patients who received IVt topotecan for NM. Primary tumors in these patients were as follows: 2 patients with primary breast cancer, 1 patient with multiple myeloma, 1 patient with medulloblastoma and 1 patient with melanoma. Results: In this series of patients, 5 months was the minimum length of treatment with IVt topotecan and maximum length of treatment was 10 months. One patient continues to receive treatment after 7 months. One patient experienced fatigue which was well controlled with dexamethasone. One patient consistently experienced nausea the day after treatment which was well controlled with compazine. There were no other adverse effects. Reasons for stopping treatment were as follows. One patient had progressive systemic disease, 2 patients experienced progression of NM, 1 patient stopped due to progressive neurological and physical decline, one patient continues treatment at this time. Conclusions: Overall, we find IVt topotecan a well tolerated and viable treatment for patients with NM originating from a variety of primary malignancies. No significant financial relationships to disclose.
A phase I study of triapine in combination with doxorubicin in refractory tumors
Authors: J. E. Chang, S. Morgan Meadows, A. Traynor, J. Kolesar, R. Marnocha, F. Lee, J. Eickoff, E. Beth, K. Binger, G. Wilding
Journal: Journal of Clinical Oncology (2006)

13168 Background: Triapine (T) is a novel ribonucleotide reductase inhibitor, affecting the M2 subunit. It has in vitro and in vivo antitumor activity. Hematologic toxicity was dose limiting in single agent phase I trials. Triapine potentiates the activity of DNA damaging agents such as doxorubicin (D), with synergy demonstrated in vivo. Methods: D was administered on day 1 and T was administered on days 1–4 of a 21-day cycle. Patients enrolled in cohorts of three, beginning at D60 mg/m 2 and T25 mg/m 2 . Dose limiting toxicity was defined as grade 3 or 4 leukopenia or thrombocytopenia lasting 7 days, febrile neutropenia or grade 3 or 4 non-hematologic toxicity. Results: Fourteen patients have enrolled in four dose cohorts, receiving 23 courses. At dose level 2 (D60 mg/m 2 , T45 mg/m 2 ), two patients experienced DLT (febrile neutropenia, grade 4 thrombocytopenia). An additional 3 patients enrolled at dose level one without initial toxicity. Enrollment then resumed at dose level 2a with a decreased dose of doxorubicin (D45 mg/m 2 , T45 mg/m 2 ). Two patients enrolled on this level had DLT. Enrollment was planned to resume at dose level 1 (D60 mg/m 2 , T25 mg/m 2 ); however, the sixth patient enrolled to this cohort developed grade 5 heart failure (ejection fraction 20%, pretreatment EF 62%) after the second course. Enrollment has begun at doses of D45 mg/m 2 and T25 mg/m 2 . Hematologic toxicity has predominated, with 52% of courses having grade 3 or 4 neutropenia. Non-hematologic toxicity included grade 2 fatigue in 17% of courses and 1 episode of grade 5 heart failure. Although no objective antitumor responses have been seen, 1 patient with metastatic melanoma had stable disease through 6 cycles of treatment. Another patient with previously rapidly progressive metastatic melanoma had stable disease for over 2 months of treatment. Conclusions: The combination of triapine and doxorubicin appears to have increased toxicity. Enrollment continues. [Table: see text]
A phase II, multicenter, randomized clinical trial to evaluate the efficacy and safety of bevacizumab in combination with either chemotherapy (docetaxel or pemetrexed) or erlotinib hydrochloride compared with chemotherapy alone for treatment of recurrent or refractory non-small cell lung cancer
Authors: L. Fehrenbacher, V. O’Neill, C. P. Belani, P. Bonomi, L. Hart, O. Melnyk, A. Sandler, D. Ramies, R. S. Herbst
Journal: Journal of Clinical Oncology (2006)

7062 Background: Bevacizumab is a recombinant, humanized anti-VEGF MAb. Erlotinib is a potent, reversible, highly selective and orally available EGFR tyrosine-kinase inhibitor. Both compounds have demonstrated a survival benefit in the treatment of NSCLC: bevacizumab when added to chemotherapy in the first line setting, and erlotinib when given alone in the 2nd/3rd line. In addition, a single arm phase I/II study of the combination of bevacizumab and erlotinib has shown encouraging survival and response rate data, with a favorable safety profile (Sandler et al, PASCO 2004). Methods: A multicenter, randomized phase II trial was conducted to evaluate the safety of combining bevacizumab with chemotherapy (docetaxel or pemetrexed), or with erlotinib; and to make a preliminary assessment of the efficacy of combining bevacizumab with chemotherapy or erlotinib relative to chemotherapy alone, as measured by progression-free survival. All patients had histologically confirmed non-squamous NSCLC and had experienced disease progression (clinical or radiological) during or following one platinum-based regimen for advanced stage disease. Randomization was on a 1:1:1 basis to docetaxel or pemetrexed plus placebo (arm 1) v docetaxel or pemetrexed plus bevacizumab (arm 2) v bevacizumab plus erlotinib (arm 3). Patients remained in the treatment phase of the study until documented radiographic or clinical disease progression or through 52 weeks of study treatment. Results: Between August 2004 and November 2005, 120 patients were randomized and treated. To date, there have been 68/85 required PFS events; arms 1 and 2 therefore remain blinded. Demographics from the first 85 patients for arms 1 &amp; 2 v 3 are as follows: median age 65 v 68;% male/female 64/36 v 44/56; ethnicity % white/black/asian/other 83/12/2/3 v 74/15/4/7; % ECOG PS 0/1/2 46/52/2 v 50/50/0; % adenocarcinoma/BAC&amp;BAC-like/Other 67/7/26 v 69/8/23; % current/previous/never-smoker 15/71/14 v 11/74/15. Conclusions: Efficacy and safety results will be presented at the meeting. [Table: see text]
Mesenchymal Tumorigenesis Driven by TSC2 Haploinsufficiency Requires HMGA2 and Is Independent of mTOR Pathway Activation
Authors: Jeanine D'Armiento, Takayuki Shiomi, Sarah Marks, Patrick Geraghty, Devipriya Sankarasharma, Kiran Chada
Journal: Cancer Research (2016)

Tuberous sclerosis (TSC) is a tumor suppressor gene syndrome that is associated with the widespread development of mesenchymal tumor types. Genetically, TSC is said to occur through a classical biallelic inactivation of either TSC genes (TSC1, hamartin or TSC2, tuberin), an event that is implicated in the induction of the mTOR pathway and subsequent tumorigenesis. High Mobility Group A2 (HMGA2), an architectural transcription factor, is known to regulate mesenchymal differentiation and drive mesenchymal tumorigenesis in vivo. Here, we investigated the role of HMGA2 in the pathogenesis of TSC using the TSC2(+/-) mouse model that similarly mirrors human disease and human tumor samples. We show that HMGA2 expression was detected in 100% of human and mouse TSC tumors and that HMGA2 activation was required for TSC mesenchymal tumorigenesis in genetically engineered mouse models. In contrast to the current dogma, the mTOR pathway was not activated in all TSC2(+/-) tumors and was elevated in only 50% of human mesenchymal tumors. Moreover, except for a subset of kidney tumors, tuberin was expressed in both human and mouse tumors. Therefore, haploinsufficiency of one TSC tumor suppressor gene was required for tumor initiation, but further tumorigenesis did not require the second hit, as previously postulated. Collectively, these findings demonstrate that tissue-specific genetic mechanisms are employed to promote tumor pathogenesis in TSC and identify a novel, critical pathway for potential therapeutic targeting.
Permanent Cell Lines From Erythrophoromas in Goldfish (&lt;italic&gt;Carassius auratus&lt;/italic&gt;)&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Jiro Matsumoto
 5, Takatoshi Ishikawa, Prince Masahito, Shozo Takayama
Journal: JNCI Journal of the National Cancer Institute (1980)

Attempts to establish permanent cell lines from spontaneous erythrophoromas (tumors derived from red pigment cells or erythrophores) of goldfish were made with the use of biopsy specimens from 12 tumors in 10 fish. Three cell lines were established that grew in vitro in synthetic medium (L-15 or Dulbecco's modified Eagle's minimum essential medium) supplemented with 20% fetal bovine serum for more than 8 months. One of these lines (GEM-81) with high proliferative activity was cultured for over 200 generations without an obvious change in growth rate. From this cell line, clonal cultures were obtained that formed clones with relatively intense yellow pigmentation. Descendants of these cell lines and clones contained low but detectable amounts of pteridine pigments (such as 7-hydroxybiopterin, biopterin, xanthopterin, and isoxanthopterin) and numerous cytoplasmic organelles analogous to pterinosomes. Both these characteristics are phenotypic markers of normal erythrophores and their neoplastic counterparts. After numerous subcultivations, these long-term cultures differed from those of the initial expiants in having much lower contents of total pteridines and relatively lowered contents of 7-hydroxybiopterin. As manifestations of their neoplastic origins, all cell lines examined showed disoriented growth with dense focal mounding in monolayer cultures. The population doubling time of the uncloned GEM-81 cell line was 31 hours at 35° C over a feeder cell layer and 3 days at 25° C without feeder cells. Injection of cultured cells (1.5×107 cells/fish) into normal goldfish that had not been immunosuppressed did not give rise to tumors within 5 months.