Neoadjuvant chemoradiotherapy is considered a standard approach for T3-4 M0 rectal cancer. In this situation, we compared neoadjuvant radiotherapy plus capecitabine with dose-intensified radiotherapy ...plus capecitabine and oxaliplatin.
We randomly assigned patients to receive 5 weeks of treatment with radiotherapy 45 Gy/25 fractions with concurrent capecitabine 800 mg/m(2) twice daily 5 days per week (Cap 45) or radiotherapy 50 Gy/25 fractions with capecitabine 800 mg/m(2) twice daily 5 days per week and oxaliplatin 50 mg/m(2) once weekly (Capox 50). The primary end point was complete sterilization of the operative specimen (ypCR).
Five hundred ninety-eight patients were randomly assigned to receive Cap 45 (n = 299) or Capox 50 (n = 299). More preoperative grade 3 to 4 toxicity occurred in the Capox 50 group (25 v 1%; P < .001). Surgery was performed in 98% of patients in both groups. There were no differences between groups in the rate of conservative surgery (75%) or postoperative deaths at 60 days (0.3%). The ypCR rate was 13.9% with Cap 45 and 19.2% with Capox 50 (P = .09). When ypCR was combined with yp few residual cells, the rate was respectively 28.9% with Cap 45 and 39.4% with Capox 50 (P = .008). The rate of positive circumferential rectal margins (between 0 and 2 mm) was 19.3% with Cap 45 and 9.9% with Capox 50 (P = .02).
The benefit of oxaliplatin was not demonstrated and this drug should not be used with concurrent irradiation. Cap 50 merits investigation for T3-4 rectal cancers.
Romiplostim, a thrombopoietic agent with demonstrated efficacy against immune thrombocytopenia (ITP) in prospective controlled studies, was recently licensed for adults with chronic ITP. Only France ...has allowed romiplostim compassionate use since January 2008. ITP patients could receive romiplostim when they failed to respond to successive corticosteroids, intravenous immunoglobulins, rituximab, and splenectomy, or when splenectomy was not indicated. We included the first 80 patients enrolled in this program with at least 2 years of follow-up. Primary platelet response (platelet count ≥ 50 × 109/L and double baseline) was observed in 74% of all patients. Long-term responses (2 years) were observed in 47 (65%) patients, 37 (79%) had sustained platelet responses with a median platelet count of 106 × 109/L (interquartile range, 75-167 × 109/L), and 10 (21%) were still taking romiplostim, despite a median platelet count of 38 × 109/L (interquartile range, 35-44 × 109/L), but with clinical benefit (lower dose and/or fewer concomitant treatment(s) and/or diminished bleeding signs). A high bleeding score and use of concomitant ITP therapy were baseline factors predicting romiplostim failure. The most frequently reported adverse events were: arthralgias (26%), fatigue (13%), and nausea (7%). Our results confirmed that romiplostim use in clinical practice is effective and safe for severe chronic ITP. This trial was registered at www.clinicaltrials.gov as #NCT01013181.
Colon cancer (CC) pathological staging fails to accurately predict recurrence, and to date, no gene expression signature has proven reliable for prognosis stratification in clinical practice, perhaps ...because CC is a heterogeneous disease. The aim of this study was to establish a comprehensive molecular classification of CC based on mRNA expression profile analyses.
Fresh-frozen primary tumor samples from a large multicenter cohort of 750 patients with stage I to IV CC who underwent surgery between 1987 and 2007 in seven centers were characterized for common DNA alterations, including BRAF, KRAS, and TP53 mutations, CpG island methylator phenotype, mismatch repair status, and chromosomal instability status, and were screened with whole genome and transcriptome arrays. 566 samples fulfilled RNA quality requirements. Unsupervised consensus hierarchical clustering applied to gene expression data from a discovery subset of 443 CC samples identified six molecular subtypes. These subtypes were associated with distinct clinicopathological characteristics, molecular alterations, specific enrichments of supervised gene expression signatures (stem cell phenotype-like, normal-like, serrated CC phenotype-like), and deregulated signaling pathways. Based on their main biological characteristics, we distinguished a deficient mismatch repair subtype, a KRAS mutant subtype, a cancer stem cell subtype, and three chromosomal instability subtypes, including one associated with down-regulated immune pathways, one with up-regulation of the Wnt pathway, and one displaying a normal-like gene expression profile. The classification was validated in the remaining 123 samples plus an independent set of 1,058 CC samples, including eight public datasets. Furthermore, prognosis was analyzed in the subset of stage II-III CC samples. The subtypes C4 and C6, but not the subtypes C1, C2, C3, and C5, were independently associated with shorter relapse-free survival, even after adjusting for age, sex, stage, and the emerging prognostic classifier Oncotype DX Colon Cancer Assay recurrence score (hazard ratio 1.5, 95% CI 1.1-2.1, p = 0.0097). However, a limitation of this study is that information on tumor grade and number of nodes examined was not available.
We describe the first, to our knowledge, robust transcriptome-based classification of CC that improves the current disease stratification based on clinicopathological variables and common DNA markers. The biological relevance of these subtypes is illustrated by significant differences in prognosis. This analysis provides possibilities for improving prognostic models and therapeutic strategies. In conclusion, we report a new classification of CC into six molecular subtypes that arise through distinct biological pathways.
Nitroxide-mediated polymerization (NMP) of β-myrcene (My) at 120 °C in bulk using unimolecular SG1-based succinimidyl ester-functionalized BlocBuilder (BB) alkoxyamine resulted in low dispersity (Đ = ...1.1–1.4) poly(myrcene)s P(My)s with high SG1 chain-end fidelity. The polymerizations also showed the number-average molecular weights (M n) increased almost linearly with conversion. SG1-terminated P(My) macroinitiators were cleanly chain-extended with styrene (S) and the S-rich P(My-b-S) diblock copolymers exhibited two distinct glass transition temperatures (T gs), indicative of microphase separation. P(My-b-S) diblocks showed brittle stress–strain behavior, plausibly due to relatively low M n. My/S mixtures with initial S molar feed compositions f S,0 = 0.10–0.94 were also statistically copolymerized (M n = 8.2–19.8 kg mol–1, Đ ≤ 1.37, and monomodal distributions). Copolymer reactivity ratios were r S = 0.25 ± 0.04/0.34 ± 0.19 and r My = 1.88 ± 0.12/2.19 ± 0.07 using Fineman–Ross and Kelen–Tüdös methods. The statistical P(My-stat-S) copolymers displayed a range of T gs (−77 to +30 °C) depending on My molar fraction. My-rich and S-rich P(My-stat-S)s were then successfully chain-extended with both S and My.
Due to their outstanding properties such as high optical transparency, high electrical resistance, high thermal insulation, good thermo-mechanical properties, and dimensional stability, epoxy ...networks play a key role in the world of thermosetting polymers. In fact, they are widely used in Industry as adhesives, paints and coatings, electrical and electronics applications as well as composite matrices for automotive and aerospace applications. Epoxy networks are issued from epoxy prepolymers composed of two to four oxirane rings able to undergo a polyaddition polymerizations with hardeners (amines, phenols, isocyanates, or acids) or a chain homopolymerization reactions in the presence of initiators such as tertiary amines, imidazoles, or ammonium salts. However, the innovations in this area have reached certain technological limits. Very recently, ionic liquids have shown their potential to be used as new initiators or functional building blocks of epoxy prepolymers and as a novel generation of epoxidized ionic liquid monomers. Thus, a new and innovative pathway has emerged producing a new generation of epoxy thermosets issue from ionic liquids by the concept of ‘function through structural design’ leading to unprecedented improvements in their physical properties. In fact, epoxy networks can be tuned with glass transition temperatures included from -40 to 170°C depending of the targeted applications. Thus, the polymer/ionic liquid synergy leads to the design and development of new dedicated (multi)functional thermosetting materials with improved properties such as ionic conductivity, chemical and thermal stability, fire retardancy, water barrier properties and mechanical performances.
The aim of this review is to point out the potential of this novel class of ionic thermoset materials in the field of epoxy thermosets.
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The ACCORD 12 trial investigated the value of two different preoperative chemoradiotherapy (CT-RT) regimens in T3-4 Nx M0 resectable rectal cancer. Clinical results are reported after follow-up of 3 ...years.
Between November 2005 and July 2008, a total of 598 patients were randomly assigned to preoperative CT-RT with CAP45 (45-Gy RT for 5 weeks with concurrent capecitabine) or CAPOX50 (50-Gy RT for 5 weeks with concurrent capecitabine and oxaliplatin). Total mesorectal excision was planned 6 weeks after CT-RT. The primary end point was sterilization of the operative specimen, which was achieved in 13.9% versus 19.2% of patients, respectively (P = .09). Clinical results were analyzed for all randomly assigned patients according to the intention-to-treat principle.
At 3 years, there was no significant difference between CAP45 and CAPOX50 (cumulative incidence of local recurrence, 6.1% v 4.4%; overall survival, 87.6% v 88.3%; disease-free survival, 67.9% v 72.7%). Grade 3 to 4 toxicity was reported in four patients in the CAP45 group and in two patients in the CAPOX50 group. Bowel continence, erectile dysfunction, and social life disturbance were not different between groups. In multivariate analysis, the sterilization rate (Dworak score) of the operative specimen was the main significant prognostic factor (hazard ratio, 0.32; 95% CI, 0.21 to 0.50).
At 3 years, no significant difference in clinical outcome was achieved with the intensified CAPOX regimen. When compared with other recent randomized trials, these results indicate that concurrent administration of oxaliplatin and RT is not recommended.
Abstract
In this study, LIonomers families based on phosphonium ILs have been successfully developed. These LIonomers are designed from the combination of various phosphonium‐based ionic liquids ...(PhILs) with different counter anions including tetradecyl (trihexyl) phosphonium bis (2,4,4‐trimethylpentyl) phosphinate (P
+
TMP), tributyl (ethyl) phosphonium diethyl phosphate (P
+
DEP), trihexyl (tetradecyl) phosphonium chloride (P
+
Cl) and trihexyl (tetradecyl) phosphonium acetate (P
+
Ac). Here, the interactions between maleic anhydride groups (MA) of the maleic anhydride‐grafted polypropylene (PPgMA) and PhILs within LIonomers have been investigated by NMR, whose intensity depends on the chemical nature of cation/anion pairs. Then, viscosity in the molten state was considered as a probe of the interaction intensity between polar groups of grafted polypropylenes and the phosphonium cation. The proper one can be tuned from the nature (P
+
TMP vs. P
+
Ac vs. P
+
Cl), from the steric hindrance, that is, relevant to the conformation of PhILs (P
+
DEP vs. P
+
TMP
/
P
+
Ac
/
P
+
Cl), and by MA content, as well as the extent of generated ionic chains from polar groups of matrices as “head” and associated anion/cation pairs. The effect of these generated ionic interactions on crystallization process and mechanical properties had been also investigated by DSC in non‐isothermal conditions, and tensile tests. Depending of the steric hindrance of the phosphonium ILs playing a key role on the interactions with PPgMA chains, an increase of the ductility versus a plasticizing effect can be obtained as function of the targeted applications.
•Development of phthalonitrile resins from 2,3-dicyanohydroquinone.•Monitoring of curing with different analysis techniques (DSC, TGA/IR, FTIR).•High resistance to thermal degradation and high char ...yields of cured resins.
In the aerospace industry, composite materials based on high-performance fibers and polymer matrices are widely used. Indeed, they can display very important mechanical and thermal properties with a very large density-to-stiffness balance. Usually, thermal protection systems are made from composite materials containing a char precursor for the polymer matrix. Temperature-resistant organic polymers are still quite rare and generally require very restrictive manufacturing and use processes. Recently, phthalonitriles have gained interest due to their very good thermostability and high char yield. However, phthalonitrile resins are generally solid at room temperature and often have a narrow processing window. In this work, synthesis methods allowing access to phthalonitrile resins were developed from 2,3-dicyanohydroquinone. These methods propose to consider together phenolic chemistry (phenolic reactive positions and aldehyde) and self-crosslinkable phthalonitrile chemistry (hydroxyl-mediated from phenolic and nitriles). It was thus possible to synthesize liquid resins at room temperature, leading to polymeric networks with a very high thermostability (temperature at 5% mass loss > 450 °C and char yield ≈ 70 %).
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