Objectives:
Recent case reports and series have shown that patients with neuromyelitis optica (NMO) experience clinical deterioration under interferon beta (IFN-β) treatment. The objective of the ...present study was to evaluate whether and to what extent IFN-β exacerbates NMO spectrum disorders (NMOSD).
Methods:
We retrospectively reviewed the medical records of 40 patients with NMOSD who had been treated with IFN-β for more than 6 months and whose disease duration was more than 1 year at the initiation of IFN-β treatment. We evaluated their annualized relapse rates (ARR) and Expanded Disability Status Scale (EDSS) scores before and after IFN-β treatment.
Results:
In total, 95% of patients exhibited an ineffective or exacerbated response to IFN-β treatment and the mean ARR significantly increased after IFN-β treatment (p = 0.002). The increased ARR > 50% under IFN-β treatment was observed in 20 patients (50%). The mean EDSS score significantly increased following IFN-β treatment (p < 0.001).
Conclusion:
In patients with NMOSD, IFN-β treatment is not only ineffective for preventing relapses but also may even increase relapses significantly. Thus, a more careful diagnostic approach to differentiate NMO from multiple sclerosis and attention to decision of treatment is warranted for patients at high risk of NMO.
Leaf senescence is a developmentally programmed cell death process that constitutes the final step of leaf development and involves the extensive reprogramming of gene expression. Despite the ...importance of senescence in plants, the underlying regulatory mechanisms are not well understood. This study reports the isolation and functional analysis of RAV1, which encodes a RAV family transcription factor. Expression of RAV1 and its homologues is closely associated with leaf maturation and senescence. RAV1 mRNA increased at a later stage of leaf maturation and reached a maximal level early in senescence, but decreased again during late senescence. This profile indicates that RAV1 could play an important regulatory role in the early events of leaf senescence. Furthermore, constitutive and inducible overexpression of RAV1 caused premature leaf senescence. These data strongly suggest that RAV1 is sufficient to cause leaf senescence and it functions as a positive regulator in this process.
To evaluate the effective dose and patterns of recurrence after stereotactic body radiation therapy (SBRT) for hepatic metastases that arise from colorectal cancer.
A cohort of 70 patients with 103 ...colorectal liver metastases were treated with SBRT at a single institution. The prescribed doses were 45 to 60 Gy in 3 to 4 fractions, but these were modified according to the tolerance of the adjacent normal tissue. To allow for dose comparisons, a biological equivalent dose was calculated.
The median follow-up period was 34.2 months (range, 5.3-121.8 months). The 2-year overall survival and progression-free survival rates were 75% and 35%, respectively. In subgroups, the 2-year local control rates for biological equivalent dose ≤80 Gy (group 1), 100 to 112 Gy (group 2), and ≥132 Gy (group 3) were 52%, 83%, and 89%, respectively. Cox proportional hazards model revealed a significant difference between groups (hazard ratio 0.44, P=.03 for group 2; hazard ratio 0.17, P=.17 for group 3; P=.01 for total). The major pattern of failure was a new liver metastasis out of the SBRT field. There was no grade ≥3 toxicity.
Stereotactic body radiation therapy of liver metastases derived from colorectal cancer offers a locally effective treatment without significant complications. Longer local control can be expected if higher doses are used. Further studies will be needed to compare the efficacies of SBRT with those of surgical resection or radiofrequency ablation.
This quasi-experimental, nonequivalent control group study developed an eight-session post-traumatic growth program for teachers who had experienced violence from students and/or parents and examined ...its effects on rumination, burnout, and post-traumatic growth. A convenience sample was recruited from 11 elementary schools in Jeonbuk province, South Korea. The experimental group (
= 27) participated in bi-weekly sessions over four weeks, whereas the control group (
= 27) read educational materials on post-traumatic growth during the same period. The experimental group exhibited significantly greater decreases in intrusive rumination and higher post-traumatic growth than the control group. The program could be an effective intervention to assist traumatized teachers.
Two new phenylspirodrimane derivatives, stachybotrysin (1) and stachybotrylactone B (2), were isolated from the cultures of the marine-derived fungus Stachybotrys sp. KCB13F013. The structures were ...determined by analyzing the spectroscopic data (1D and 2D NMR and MS) and chemical transformation, including the modified Mosher’s method and single-crystal X-ray structure analysis. Compound 1 exhibited an inhibitory effect on osteoclast differentiation in bone marrow macrophage cells via suppressing the RANKL-induced activation of p-ERK, p-JNK, p-p38, c-Fos, and NFATc1.
Lymphovascular and perineural invasion are well-known negative prognostic indicators in rectal cancer, but previous studies on their significance are not consistent.
This study assessed the ...prognostic value of lymphovascular and perineural invasion in rectal cancer patients who received preoperative chemoradiotherapy followed by curative resection.
This is a retrospective analysis.
This study was performed at a tertiary cancer center.
Rectal cancer patients who underwent curative resection after preoperative chemoradiotherapy between January 2000 and December 2010.
The primary outcomes were disease-free survival and overall survival. The survival rates were estimated using Kaplan-Meier analysis, and group comparisons were conducted using a log-rank test.
Of the 1156 included patients, 109 (9.4%) presented with lymphovascular invasion and 137 (11.9%) presented with perineural invasion. Lymphovascular and perineural invasion were associated with T and N downstaging after preoperative chemoradiotherapy ( p < 0.001). In the ypN0 patients, the 5-year disease-free survival rates were 70.8% and 78.5% ( p = 0.150) for the lymphovascular invasion and absent groups, respectively. In the perineural invasion group, the 5-year disease-free survival rate was 59.0% compared to 80.2% in the absent group ( p = 0.001). Among the ypN+ patients, the 5-year disease-free survival rates were 36.9% and 44.4% for the lymphovascular invasion and absent groups, respectively ( p = 0.211). The perineural invasion group had a poorer 5-year disease-free survival rate compared to the absent group (29.7% vs 46.7%; p = 0.011). By multivariable analyses, perineural invasion correlated with a poor disease-free survival (HR 1.412, 95% CI 1.082-1.843; p = 0.011) and also in ypN0 subgroup analysis (HR 1.717, 95% CI 1.093-2.697; p = 0.019).
This study was a retrospective study conducted at a single center.
Perineural invasion is a reliable independent predictor of recurrence in rectal cancer patients treated with preoperative chemoradiotherapy. Patients with perineural invasion should be considered for closer surveillance even with ypN0 status. See Video Abstract at http://links.lww.com/DCR/B833 .IMPLICACIÓN CLÍNICA DE LA INVASIÓN PERINEURAL Y LINFOVASCULAR EN PACIENTES CON CÁNCER DE RECTO SOMETIDOS A CIRUGÍA DESPUÉS DE QUIMIORRADIOTERAPIA PREOPERATORIA.
La invasión linfovascular y perineural en cancer de recto, son indicadores pronósticos negativos bien conocidos, pero estudios previos sobre su significancia, no son consistentes.
El estudio evaluó el valor pronóstico de la invasión linfovascular y perineural en pacientes con cáncer de recto sometidos a quimiorradioterapia preoperatoria seguida de resección curativa.
Es un análisis retrospectivo.
El estudio se realizó en un centro oncológico terciario.
Pacientes con cáncer de recto sometidos a resección curativa después de quimiorradioterapia preoperatoria entre enero de 2000 y diciembre de 2010.
Los resultados primarios fueron la supervivencia libre de enfermedad y la supervivencia general. Las tasas de supervivencia se estimaron mediante el análisis de Kaplan-Meier y las comparaciones de grupos se realizaron mediante una prueba de rango logarítmico.
De los 1156 pacientes incluidos, 109 (9,4%) presentaron invasión linfovascular y 137 (11,9%) invasión perineural. La invasión linfovascular y perineural se asoció con reducción del estadio de T y N después de la quimiorradioterapia preoperatoria ( p < 0,001). En los pacientes ypN0, las tasas de supervivencia libre de enfermedad a 5 años fueron del 70,8% y el 78,5% ( p = 0,150) para los grupos con y sin invasión linfovascular, respectivamente. En el grupo de invasión perineural, la tasa de supervivencia libre de enfermedad a 5 años fue del 59,0%, en comparación con el 80,2% en el grupo ausente ( p = 0,001). Entre los pacientes ypN +, las tasas de supervivencia sin enfermedad a 5 años fueron del 36,9% y 44,4% para los grupos con y sin invasión linfovascular, respectivamente ( p = 0,211). El grupo de invasión perineural mostró una tasa de supervivencia libre de enfermedad a 5 años menor, en comparación con el grupo ausente (29,7% versus 46,7%, p = 0,011). Mediante análisis multivariable, la invasión perineural se correlacionó con una pobre tasa de supervivencia de enfermedad (índice de riesgo 1,412; intervalo de confianza del 95%: 1,082-1,843; p = 0,011) y también en el análisis de subgrupos ypN0 (índice de riesgo 1,717; intervalo de confianza del 95%: 1,093-2,697; p = 0,019).
Estudio retrospectivo realizado en un solo centro.
La invasión perineural es un predictor independiente y confiable de recurrencia en pacientes con cáncer de recto tratados con quimiorradioterapia preoperatoria. Los pacientes con invasión perineural deben considerarse para una vigilancia más estrecha incluso con estadio ypN0. Consulte Video Resumen en http://links.lww.com/DCR/B833 . (Traducción-Dr. Fidel Ruiz Healy ).
Analysis of the genome sequence of Streptomyces sp. KCB13F003 showed the presence of a cryptic gene cluster encoding flavin-dependent halogenase and nonribosomal peptide synthetase. Pleiotropic ...approaches using multiple culture media followed by LC-MS-guided isolation and spectroscopic analysis enabled the identification of two new chlorinated cyclic hexapeptides, ulleungmycins A and B (1 and 2). Their structures, including absolute configurations, were determined by 1D and 2D NMR techniques, advanced Marfey’s analysis, and GITC derivatization. The new peptides, featuring unusual amino acids 5-chloro-l-tryptophan and d-homoleucine, exhibited moderate antibacterial activities against Gram-positive pathogenic bacteria including methicillin-resistant and quinolone-resistant Staphylococcus aureus.
Autophagy plays an important role in maintaining tumor cell progression and survival in response to metabolic stress. Thus, the regulation of autophagy can be used as a strategy for anticancer ...therapy. Here, we report dutomycin (DTM) as a novel autophagy enhancer that eventually induces apoptosis due to excessive autophagy. Also, human serine protease inhibitor B6 (SERPINB6) was identified as a target protein of DTM, and its novel function which is involved in autophagy was studied for the first time. We show that DTM directly binds SERPINB6 and then activates intracellular serine proteases, resulting in autophagy induction. Inhibitory effects of DTM on the function of SERPINB6 were confirmed through enzyme- and cell-based approaches, and SERPINB6 was validated as a target protein using siRNA-mediated knockdown and an overexpression test. In a zebrafish xenograft model, DTM showed a significant decrease in tumor area. Furthermore, the present findings will be expected to contribute to the expansion of novel basic knowledge about the correlation of cancer and autophagy by promoting active further research on SERPINB6, which was not previously considered the subject of cancer biology.
Hypoxia-inducible factor-1α (HIF-1α) mediates tumor cell adaptation to hypoxic conditions and is a potentially important anticancer therapeutic target. We previously developed a method for ...synthesizing a benzofuran-based natural product, (R)-(-)-moracin-O, and obtained a novel potent analog, MO-460 that suppresses the accumulation of HIF-1α in Hep3B cells. However, the molecular target and underlying mechanism of action of MO-460 remained unclear. In the current study, we identified heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) as a molecular target of MO-460. MO-460 inhibits the initiation of HIF-1α translation by binding to the C-terminal glycine-rich domain of hnRNPA2B1 and inhibiting its subsequent binding to the 3'-untranslated region of HIF-1α mRNA. Moreover, MO-460 suppresses HIF-1α protein synthesis under hypoxic conditions and induces the accumulation of stress granules. The data provided here suggest that hnRNPA2B1 serves as a crucial molecular target in hypoxia-induced tumor survival and thus offer an avenue for the development of novel anticancer therapies.
Background Preoperative (chemo)radiotherapy has been widely used as an effective treatment for locally advanced rectal cancer (LARC), leading to a significant reduction in pelvic recurrence rates. ...Because early administration of intensive chemotherapy for LARC has more advantages than adjuvant chemotherapy, total neoadjuvant therapy (TNT) has been introduced and evaluated to determine whether it can improve tumor response or treatment outcomes. This study aims to investigate whether short-course radiotherapy (SCRT) followed by intensive chemotherapy improves oncologic outcomes compared with traditional preoperative long-course chemoradiotherapy (CRT). Methods A multicenter randomized phase II trial involving 364 patients with LARC (cT3-4, cN+, or presence of extramural vascular invasion) will be conducted. Patients will be randomly assigned to the experimental or control arm at a ratio of 1:1. Participants in the experimental arm will receive SCRT (25 Gy in 5 fractions, daily) followed by four cycles of FOLFOX (oxaliplatin, 5-fluorouracil, and folinic acid) as a neoadjuvant treatment, and those in the control arm will receive conventional radiotherapy (45-50.4 Gy in 25-28 fractions, 5 times a week) concurrently with capecitabine or 5-fluorouracil. As a mandatory surgical procedure, total mesorectal excision will be performed 2-5 weeks from the last cycle of chemotherapy in the experimental arm and 6-8 weeks after the last day of radiotherapy in the control arm. The primary endpoint is 3-year disease-free survival, and the secondary endpoints are tumor response, overall survival, toxicities, quality of life, and cost-effectiveness. Discussion This is the first Korean randomized controlled study comparing SCRT-based TNT with traditional preoperative LC-CRT for LARC. The involvement of experienced colorectal surgeons ensures high-quality surgical resection. SCRT followed by FOLFOX chemotherapy is expected to improve disease-free survival compared with CRT, with potential advantages in tumor response, quality of life, and cost-effectiveness. Trial registration This trial is registered at Clinical Research Information under the identifier Service KCT0004874 on April 02, 2020, and at Clinicaltrial.gov under the identifier NCT05673772 on January 06, 2023. Keywords: Rectal neoplasm, Neoadjuvant radiotherapy, Short-course radiation, Consolidation chemotherapy, Disease-free survival, Randomized controlled phase II trial, Protocol
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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