Lenalidomide-rituximab therapy is effective in grade 1-2 follicular and mantle cell lymphoma, but its efficacy in diffuse large B-cell lymphoma (DLBCL), transformed large cell lymphoma (TL) and grade ...3 follicular lymphoma (FLG3) is unknown. In this phase II trial, 45 patients with relapsed or refractory DLBCL (n=32), TL (n=9) or FLG3 (n=4) who had received 1-4 prior lines of treatment were given 20 mg oral lenalidomide on days 1-21 of each 28-day cycle, and intravenous rituximab (375 mg/m(2)) weekly during cycle 1. Grade 3/4 hematological toxicities included neutropenia (53%), lymphopenia (40%), thrombocytopenia (33%), leukopenia (27%) and anemia (18%), with a median follow-up time of 29.1 months (range 14.7-52.0 months). Overall response (OR) rate was 33%; median response duration was 10.2 months. Median progression-free survival (PFS) and overall survival (OS) were 3.7 and 10.7 months, respectively. Nine of the 15 responding patients (three partial response (PR), six complete response (CR)) proceeded with stem cell transplantation (SCT) and were censored at the time of transplantation. When data were analyzed without censoring, median PFS remained 3.7 months and response duration increased to 30.9 months. Rituximab plus oral lenalidomide is well tolerated and effective for patients with relapsed/refractory DLBCL and TL. SCT after lenalidomide-rituximab is associated with prolonged response duration.
Cutaneous T-cell lymphomas (CTCLs) and its common variants mycosis fungoides (MF) and leukemic Sézary syndrome (SS) are rare extranodal non-Hodgkin's lymphomas. Patients who present with advanced ...disease and large-cell transformation (LCT) are incurable with standard treatments. In this article, we report the largest single-center experience with allogeneic stem-cell transplantation (SCT) for advanced CTCL.
This is a prospective case series of 47 CTCL patients who underwent allogeneic SCT after failure of standard therapy between July 2001 and September 2013. The Kaplan–Meier method was used to estimate overall survival (OS) and progression-free survival (PFS) curves. The method of Fine and Gray was used to fit regression models to the same covariates for these cumulative incidence data.
The Kaplan–Meier estimates of OS and PFS at 4 years were 51% and 26%, respectively. There was no statistical difference in the OS in patients who had MF alone, SS, MF with LCT, or SS with LCT. PFS at 4 years was superior in patients who had SS versus those who did not (52.4% versus 9.9%; P = 0.02). The cumulative incidences of grade 2–4 acute graft-versus-host disease (GVHD) and chronic GVHD were 40% and 28%, respectively. The cumulative nonrelapse mortality rate was 16.7% at 2 years.
Allogeneic SCT may result in long-term remissions in a subset of patients with advanced CTCL. Although post-SCT relapse rates are high, many patients respond to immunomodulation and achieve durable remissions.
NCT00506129.
Natural fires represent a frequent and widespread disturbance in many environments around the world and consequently plays important roles on ecosystem dynamics. The goal of our study was to evaluate ...the short-term effects of fire on termites in a tropical mountain ecosystem of the Brazilian Cerrado (savanna). Termites were sampled in unburned and burned areas 2 weeks after an extensive fire event. Sampling method consisted of toilet paper baits placed at three elevations: 800 m (Cerrado woodland habitat), 1100 and 1400 m (
campo rupestre
vegetation type). A total of 19 termite species were sampled, of which 15 occurred at 800 m, eight at 1100 m, and two at 1400 m. Average termite species richness and bait colonization were lower at 1400 m compared with the other elevations, which did not differ from each other. No effect of fire on average species richness and bait colonization was found for any elevation. As termites are known to be strongly affected by climate, soil, and vegetation, termite assemblages are probably being filtered physiologically by environmental conditions along the elevation gradient. The high tolerance of termites to fire effects is likely associated with the strategy of many collected species in constructing hard clay mounds, either above or below ground, or taking shelter in mounds built by other termite species to escape fire. We conclude that while termites are sensitive to environmental changes in conditions along the elevation gradient, they are also highly tolerant to fire in this tropical mountain.
Phosphorus (P) is a finite, non-renewable, and natural resource and a vital major nutrient for plant metabolic and developmental processes. However, adverse soil biogeochemical characteristics of ...alkaline-calcareous soils (especially Aridisols) and highly weathered acid soils (i.e., Ultisols and Oxisols) render orthophosphate (Pi) as the least available major nutrient due to P complexation, sorption, and/or fixation. In such soil environments, plant bioavailable P is only a small fraction of total soil P, seriously limiting crop growth and production. Different plant species, and even cultivars of the same species, may display a suite of growth responses that enable them to solubilize and scavenge soil P either by enhancing external Pi acquisition or reprioritizing internal Pi use under P-stress soil environments. This paper reports relative growth responses, P acquisition and P-use efficiency characteristics by 14 cultivars of spring wheat (Triticum aestivum L.) grown in solution culture with high/low P supply induced by applying soluble NH
4
H
2
PO
4
, sparingly soluble rock phosphate, and Ca
3
(PO
4
)
2
. The wheat cultivars exhibited considerable genetic diversity in biomass accumulation, P concentrations, P contents, factor (PSF) and P efficiency characteristics i.e., P utilization efficiency (PUE), P efficiency (PE), and PE ratio (PER). Plant growth and PE parameters were significantly correlated, while P uptake was linearly related with biomass increase and solution pH decrease. The wheat cultivars with high PUE, PER and P uptake, and low PSF, and plant P concentration were more efficient in utilizing P and, hence, more tolerant under P-stress environment. Biomass and P contents of "P efficient/low-P tolerant" wheat cultivars were superior to "P inefficient/low-P sensitive" cultivars at all P-stress levels. Hence, "P efficient/low-P tolerant" cultivars are the most desirable wheat genotypes for P-stress environments because they are able to scavenge more P from sparingly soluble P sources or soil-bound P forms.
Angiogenesis is very important in clinical features of pituitary adenomas. We investigated the relationship between the blood flow of nonfunctioning pituitary macroadenomas measured by arterial ...spin-labeled perfusion imaging and the microvessel attenuation of the tissue.
Conventional MR imaging with contrast-enhanced T1WI and arterial spin-labeled perfusion imaging were performed before surgery in 11 consecutive patients with nonfunctioning pituitary macroadenomas. ROIs were drawn on the tumors, and the degrees of enhancement were calculated by dividing the signal intensity on the contrast-enhanced T1WI by that on the nonenhanced TIWI. As an index of tumor perfusion, a quantitative analysis was performed by using normalized tumor blood flow values calculated by dividing the mean value of the tumor region of interest by the mean region of interest values in the 2 cerebellar hemispheres. The relative microvessel attenuation was determined as the total microvessel wall area divided by the entire tissue area on CD-31-stained specimens. The degree of enhancement and the normalized tumor blood flow values were compared with relative microvessel attenuation. Additionally, intra- and postoperative tumor hemorrhages were visually graded.
The degree of enhancement was not correlated with relative microvessel attenuation. Statistically significant correlations were observed between normalized tumor blood flow values and relative microvessel attenuation (P < .05). At surgery, 3 cases were visually determined to be hypervascular tumors, and 1 of these cases had symptomatic postoperative hemorrhage. A statistically significant difference in normalized tumor blood flow values was observed visually between the intraoperative hypovascular and hypervascular groups (P < .05).
Arterial spin-labeled perfusion imaging reflects the vascular density of nonfunctioning pituitary macroadenomas, which may be useful in the preoperative prediction of intra- and postoperative tumor hemorrhage.
Summary
Neuropeptide Y (NPY) causes various central and peripheral actions through activation of G‐protein‐coupled NPY receptors. Although a species‐dependent difference in cardiac actions of NPY has ...been reported, the responses to NPY have not been examined in mice, widely used experimental animals. This study aimed to clarify the responses to NPY and the receptor subtype involved in the responses in mouse atrium.
Neuropeptide Y caused negative inotropic and negative chronotropic actions in spontaneous beating right atria. Negative inotropic actions were more marked than negative chronotropic actions. Therefore, negative inotropic actions were studied in detail for evaluation of the NPY‐induced cardiac actions in mouse atrium.
Neuropeptide Y‐induced negative inotropic actions were not affected by atropine but were abolished in the atria from pertussis toxin‐treated mice.
In isolated atrial preparations from reserpine‐treated mice, NPY‐induced negative inotropic actions were significantly attenuated.
Leu31, Pro34‐NPY, but not peptide YY, was effective in decreasing spontaneous contraction in atrial preparations.
Although Y1, Y2, Y4 and Y5 receptor mRNAs were expressed almost equally in the brain, NPY1 receptor mRNA was dominantly expressed in the atrium.
In conclusion, NPY caused negative inotropic and chronotropic actions through activation of the Y1 receptor in the mouse atrium. A high expression level of Y1 mRNA in the atrium suggests a functional role of NPY in the regulation of mouse cardiac contraction.
Purpose: Japan has only a few respiratory disease-specific activity of daily living scales that are accepted outside of Japan, and they are not widely used. The Barthel Index dyspnea (BI-d), an ...improved version of the Barthel Index (BI), may be popular in Japan. The purpose of this study was to develop the Japanese version of BI-d (J-BI-d) and investigate its reliability and validity. Patients and Methods: The J-BI-d was developed using the basic guidelines for scale translation. The study included patients with chronic respiratory disease, receiving outpatient care at two centers between January 2019 and February 2020. Scores on the J-BI-d, modified Medical Research Council scale (mMRC scale), BI, respiratory function tests, and 6-minute walk distance (6MWD) test were measured. To verify the test-retest reliability, the J-BI-d was re-administered, and the intraclass correlation coefficient (ICC) was obtained. Internal consistency was verified by Cronbach's alpha reliability coefficient, and criterion-related validity was verified through a correlation analysis of the J-BI-d with mMRC scale and 6MWD test. Divergent validity was verified through correlation analysis between the J-BI-d and BI. Results: Data for 57 participants (mean age 74.4 + or - 8.3 years) were analyzed, and reliability testing was performed with 42 of them. The mean time to retest was 8.1 + or - 3.0 days, and the ICC (2, 1) was 0.76 (95% CI: 0.62-0.85), indicating high reliability. Cronbach's alpha reliability coefficient was 0.81, indicating high internal consistency. Correlation coefficients of the J-BI-d with 6MWD test (r = -0.46, p < 0.01) and mMRC scale (p = 0.76, p < 0.01) indicated high criterion-related validity. The J-BI-d and BI had a weak negative correlation (r = -0.29, p < 0.05), indicating high divergent validity. Conclusion: The results of this study demonstrate high reliability and appropriate validity of the J-BI-d in patients with chronic respiratory disease. Keywords: activities of daily living, dyspnea, chronic obstructive pulmonary disease, interstitial lung disease, Japanese, reliability and validity
The proteasome has emerged as an important clinically relevant target for the treatment of hematologic malignancies. Since the Food and Drug Administration approved the first-in-class proteasome ...inhibitor bortezomib (Velcade) for the treatment of relapsed/refractory multiple myeloma (MM) and mantle cell lymphoma, it has become clear that new inhibitors are needed that have a better therapeutic ratio, can overcome inherent and acquired bortezomib resistance and exhibit broader anti-cancer activities. Marizomib (NPI-0052; salinosporamide A) is a structurally and pharmacologically unique β-lactone-γ-lactam proteasome inhibitor that may fulfill these unmet needs. The potent and sustained inhibition of all three proteolytic activities of the proteasome by marizomib has inspired extensive preclinical evaluation in a variety of hematologic and solid tumor models, where it is efficacious as a single agent and in combination with biologics, chemotherapeutics and targeted therapeutic agents. Specifically, marizomib has been evaluated in models for multiple myeloma, mantle cell lymphoma, Waldenstrom's macroglobulinemia, chronic and acute lymphocytic leukemia, as well as glioma, colorectal and pancreatic cancer models, and has exhibited synergistic activities in tumor models in combination with bortezomib, the immunomodulatory agent lenalidomide (Revlimid), and various histone deacetylase inhibitors. These and other studies provided the framework for ongoing clinical trials in patients with MM, lymphomas, leukemias and solid tumors, including those who have failed bortezomib treatment, as well as in patients with diagnoses where other proteasome inhibitors have not demonstrated significant efficacy. This review captures the remarkable translational studies and contributions from many collaborators that have advanced marizomib from seabed to bench to bedside.
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