Using New Vaginal Doses Evaluation System to Assess the Dose-Effect Relationship for Vaginal Stenosis After Definitive Radio(Chemo)Therapy for Cervical Cancer.

Objective: The study aims to investigate if a relationship exists between vaginal doses and vaginal stenosis (VS) using posterior-inferior border of symphysis (PIBS) points and the International Commission on Radiation Units-Rectum (ICRU-R) point evaluation system for definitive radio(chemo)therapy in locally advanced cervical cancer. Methods and Materials: From a vaginal dose study in China, 351 patients were prospectively assessed. For every reference point of the PIBS system and ICRU-R point was calculated for all BT and summed with EBRT. Pearson's chi-square test and Student's unpaired t-test compared variables with and without vaginal stenosis (VS) G ≥2. The risk factors were assessed for VS G ≥2 in multi- and univariate analyses through Cox proportional hazards model followed by a dose-effect curve construction. The VS morbidity rate was compared via the log-rank test using the median vaginal reference length (VRL). Results: The patients (38-month median follow-up) had 21.3% three-year actuarial estimate for VS G ≥2. Compared to G <2 patients, VS G ≥2 patients received higher doses to PIBS points except for PIBS - 2 and had significantly shorter VRL. VRL (HR = 1.765, P = 0.038), total EBRT and BT ICRU-R point dose (HR = 1.017, p = 0.003) were risk factors for VS. With VRL >4.6 cm, the 3-year actuarial estimate was 12.8% vs. 29.6% for VRL ≤4.6 cm. According to the model curve, the risks were 21, 30, and 39% at 75, 85, and 95 Gy, respectively (ICRU-R point dose). Conclusions: PIBS system point doses correlated with late vaginal toxicity. VRL combined with both EBRT and BT dose to the ICRU-R point contribute to VS risk.

Folic acid modified TPGS as a novel nano-micelle for delivery of nitidine chloride to improve apoptosis induction in Huh7 human hepatocellular carcinoma.

BACKGROUND: The development of novel and effective drugs for targeted human hepatocellular carcinoma still remains a great challenge. The alkaloid nitidine chloride (NC), a component of a traditional Chinese medicine, has been shown to have anticancer properties, but doses at therapeutic levels have unacceptable side effects. Here we investigate folic acid modified D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS-FA) as a potential carrier for controlled delivery of the drug. METHODS: Synthesized TPGS-FA was characterized by FTIR, UV-visible and 1H NMR spectroscopy, and TPGS loaded with NC was evaluated for its ability to induce apoptosis in Huh7 cells by Annexin V/PI and MTT assays, and observed by laser scanning confocal microscopy and inverted phase contrast microscopy. RESULTS: TPGS-FA/NC complexes were prepared successfully, and were homogenious with a uniform size of ~ 14 nm diameter. NC was released from the TPGS-FA/NC complexes in a controlled and sustained manner under physiological conditions (pH 7.4). Furthermore, its cytotoxicity to hepatocarcinoma cells was greater than that of free NC. CONCLUSIONS: TPGS-FA is shown to be useful carrier for drugs such as NC, and TPGS-FA/NC could potentially be a potent and safe drug for the treatment of hepatocellular carcinoma.

Successful treatment of a 19-year-old patient with locally advanced clear cell adenocarcinoma of the uterine cervix using recombinant human adenovirus type 5 (Oncorine) combined with chemoradiotherapy: a case report.

Clear cell adenocarcinoma (CCAC) of the uterine cervix is a rare histological subtype of cervical cancer. The optimal treatment paradigm for this tumor has not yet been established. In recent years, oncolytic viruses have become a promising strategy for cancer treatment. However, the role of oncolytic viruses in treating CCAC of the uterine cervix is unclear. We report a case study of a 19-year-old woman with locally advanced CCAC of the uterine cervix. The patient was first treated with external beam radiation therapy (50 Gy/25 f) and chemotherapy (cisplatin, 40 mg/m2/week, 5 weeks) with only slight reduction of the cervical tumor (45 mm × 34 mm × 51 mm). After receiving one cycle of intratumor injection therapy of Oncorine (5.0×1011 virus particles daily, from day 1 to day 5), her cervical tumor was dramatically reduced (29 mm × 26 mm × 24 mm). Subsequently, the patient received two cycles of intratumor injection therapy of Oncorine combined with brachytherapy (7 fractions) and chemotherapy (cisplatin and paclitaxel). No serious adverse events occurred during treatment. The results at the 7-month follow-up showed that the patient achieved complete response. Our case was a successful exploration of Oncorine in the treatment of locally advanced CCAC of the uterine cervix, which supports the use of oncolytic viruses as a promising treatment option for young women with this tumor.

Asymmetric Transfer Hydrogenation of rac-α-(Purin-9-yl)cyclopentones via Dynamic Kinetic Resolution for the Construction of Carbocyclic Nucleosides.

An asymmetric transfer hydrogenation via dynamic kinetic resolution of a broad range of rac- α-(purin-9-yl)cyclopentones was first developed. A series of cis-ß-(purin-9-yl)cyclopentanols were obtained with up to 97% yield, >20/1 dr, and >99% ee. This also provides an efficient synthetic route to a variety of chiral carbocyclic nucleosides.

Cyclization Reaction of Donor-Acceptor Oxiranes with N,N'-Disubstituted Thioureas: A Domino Process to trans-Dihydropyrimidines.

An unprecedented cyclization reaction of donor-acceptor oxiranes with N,N'-disubstituted thioureas to construct trans-dihydropyrimidines is presented. Preliminary reaction mechanism studies demonstrated that the reaction underwent sequential cycloaddition/amine ester exchange/oxygen-sulfur exchange/desulfuration/Michael addition process. A wide range of trans-dihydropyrimidines were produced with high yields up to 94% by using this method.

Synthesis of Chiral Six-Membered Carbocyclic Purine Nucleosides via Organocatalytic Enantioselective [3 + 3] Annulation.

A direct route to chiral six-membered carbocyclic purine nucleoside analogues with three chiral stereocenters, including a chiral tetrasubstituted carbon center, via a highly enantioselective [3 + 3] annulation has been established. With the application of Takemoto's catalyst, various chiral six-membered carbocyclic purine nucleoside analogues were obtained in high yields (up to 89%) with moderate to good diastereoselectivities (up to 90:10 dr) and excellent enantioselectivities (92-98% ee). Furthermore, diverse chiral six-membered carbocyclic purine nucleoside analogues were generated by simple transformations.

Enantioselective Synthesis of Carbocyclic Nucleosides via Asymmetric [3 + 2] Annulation of α-Purine-Substituted Acrylates with MBH Carbonates.

An efficient route to chiral carbocyclic nucleoside analogues containing a quaternary stereocenter and a C═C double bond has been established via a highly enantioselective [3 + 2] annulation of Morita-Baylis-Hillman (MBH) carbonates with α-purine-substituted acrylates. With 20 mol % (S)-SITCP as the catalyst, various chiral carbocyclic nucleoside analogues with a quaternary stereocenter and a C═C double bond were obtained in high yields (up to 92%) with good diastereoselectivities (up to 10:1 dr) and excellent enantioselectivities (up to 96% ee). Furthermore, the corresponding products were subjected to diverse transformations to afford interesting and potentially useful chiral carbocyclic nucleosides.

Redetermination of µ-oxido-bis-[bis-(N,N-diethyl-hydroxyl-aminato)-oxido-vanadium(V)].

In comparison with the previous determination [Saussine, Mimoun, Mitschler & Fisher (1980 ▶). Nouv. J. Chim.4, 235-237] of the title compound, [V(2)(C(4)H(10)NO)(4)O(3)], the current study reports an improved precision of the derived geometric parameters, along with the deposition of all coordinates and displacement parameters. The two V(V) atoms are each surrounded by two deprotonated N,O-bidentate diethyl-hydroxy-laminate groups, and a terminal and a bridging oxide ligand, in a distorted octa-hedral coordination geometry. The crystal packing is accomplished by van der Waals inter-actions.

A three-dimensional supramolecular vanadium hydroxylamide complex: poly[di-mu2-aqua-bis(hydroxylamido)-mu3-malonato-oxidosodiumvanadium(V)].

The crystal structure of the title compound, [NaV(C3H2O4)(NH2O)2O(H2O)2], is built up of NaO6 and VO5N2 polyhedra connected through malonate bridges. The NaO6 octahedra are linked by edge sharing in the equatorial plane to form one-dimensional infinite chains. These chains are linked together by the malonate bridges to form two-dimensional layers. The distorted VO5N2 pentagonal bipyramid is grafted on to the layer by a malonate carboxylate O atom. Adjacent layers are connected through O-H...O and N-H...O hydrogen bonds to build up a three-dimensional supramolecular structure.

[Root canal therapy opportunity in replanted teeth due to injury.].

PURPOSE: To investigate the opportunity of different root canal therapies in replantation of tooth due to injury. METHODS: 49 cases with teeth luxation were randomly divided into three groups. In group A, the pulp was removed before replanted, and calcium hydroxide was filled in root canals and condensated routinely after half a year. In group B, the pulp was removed one week after being replanted. In group C, the pulp was removed until pulp disease. RESULTS: The effect of group A(81.25%) and B (94.44%) was better than group C (53.33%), P<0.05. And the effect of group A and B was similar. CONCLUSION: It's an ideal method to replant luxated tooth within 3 hours with removal of pulp tissue, root canal filling with calcium hydroxide one week after replantation of tooth and condensated routine root canal therapy after half a year.