Background

To compare the periodical incidence rates of genitourinary (GU) and gastrointestinal (GI) toxicity in patients who underwent prostate low-dose-rate brachytherapy between the monotherapy group (seed implantation alone) and the boost group (in combination with external beam radiation therapy (EBRT)).

Methods

A total of 218 patients with a median follow-up of 42.5 months were enrolled. The patients were divided into 2 groups by treatment modality, namely, the monotherapy group (155 patients) and the boost group (63 patients). The periodical incidence rates of GU and GI toxicity were separately evaluated and compared between the monotherapy group and the boost group using the National Cancer Institute - Common Terminology Criteria for Adverse Events, version 3.0. To elucidate an independent factor among clinical and postdosimetric parameters to predict grade 2 or higher GU and GI toxicity in the acute and late phases, univariate and multivariate logistic regression analyses were carried out.

Results

Of all patients, 78.0% showed acute GU toxicity, and 7.8% showed acute GI toxicity, while 63.8% showed late GU toxicity, and 21.1% showed late GI toxicity. The incidence rates of late GU and GI toxicity were significantly higher in the boost group. Multivariate analysis showed that the International Prostate Symptom Score (IPSS) before seed implantation was a significant parameter to predict acute GU toxicity, while there were no significant predictive parameters for acute GI toxicity. On the other hand, combination with EBRT was a significant predictive parameter for late GU toxicity, and rectal volume (mL) receiving 100% of the prescribed dose (R100) was a significant predictive parameter for late GI toxicity.

Conclusions

The boost group showed higher incidence rates of both GU and GI toxicity. Higher IPSS before seed implantation, combination with EBRT and a higher R100 were significant predictors for acute GU, late GU and late GI toxicity.

Background

To clarify the significant clinicopathological and postdosimetric parameters to predict PSA bounce in patients who underwent low-dose-rate brachytherapy (LDR-brachytherapy) for prostate cancer.

Methods

We studied 200 consecutive patients who received LDR-brachytherapy between July 2004 and November 2008. Of them, 137 patients did not receive neoadjuvant or adjuvant androgen deprivation therapy. One hundred and forty-two patients were treated with LDR-brachytherapy alone, and 58 were treated with LDR-brachytherapy in combination with external beam radiation therapy. The cut-off value of PSA bounce was 0.1 ng/mL. The incidence, time, height, and duration of PSA bounce were investigated. Clinicopathological and postdosimetric parameters were evaluated to elucidate independent factors to predict PSA bounce in hormone-naïve patients who underwent LDR-brachytherapy alone.

Results

Fifty patients (25%) showed PSA bounce and 10 patients (5%) showed PSA failure. The median time, height, and duration of PSA bounce were 17 months, 0.29 ng/mL, and 7.0 months, respectively. In 103 hormone-naïve patients treated with LDR-brachytherapy alone, and univariate Cox proportional regression hazard model indicated that age and minimal percentage of the dose received by 30% and 90% of the urethra were independent predictors of PSA bounce. With a multivariate Cox proportional regression hazard model, minimal percentage of the dose received by 90% of the urethra was the most significant parameter of PSA bounce.

Conclusions

Minimal percentage of the dose received by 90% of the urethra was the most significant predictor of PSA bounce in hormone-naïve patients treated with LDR-brachytherapy alone.

The title compound, C10H8O6, a promising raw material to obtain colorless polyimides which are applied to microelectronic and optoelectronic devices, adopts a folded conformation in which the dihedral angle between the two anhydro rings is 55.15 (8)°. The central six-membered ring assumes a conformation inter­mediate between boat and twist-boat. In the crystal, mol­ecules are linked by weak C—H⋯O inter­actions, forming a layer parallel to the bc plane.

Nimustine (ACNU) and temozolomide (TMZ) are DNA alkylating agents which are commonly used in chemotherapy for glioblastomas. ACNU is a DNA cross-linking agent and TMZ is a methylating agent. The therapeutic efficacy of these agents is limited by the development of resistance. In this work, the role of the Fanconi anemia (FA) repair pathway for DNA damage induced by ACNU or TMZ was examined. Cultured mouse embryonic fibroblasts were used: FANCA−/−, FANCC−/−, FANCA−/−C−/−, FANCD2−/− cells and their parental cells, and Chinese hamster ovary and lung fibroblast cells were used: FANCD1/BRCA2mt, FANCG−/− and their parental cells. Cell survival was examined after a 3 h ACNU or TMZ treatment by using colony formation assays. All FA repair pathways were involved in ACNU-induced DNA damage. However, FANCG and FANCD1/BRCA2 played notably important roles in the repair of TMZ-induced DNA damage. The most effective molecular target correlating with cellular sensitivity to both ACNU and TMZ was FANCD1/BRCA2. In addition, it was found that FANCD1/BRCA2 small interference RNA efficiently enhanced cellular sensitivity toward ACNU and TMZ in human glioblastoma A172 cells. These findings suggest that the down-regulation of FANCD1/BRCA2 might be an effective strategy to increase cellular chemo-sensitization towards ACNU and TMZ.

We synthesized C5-modified analogs of 2′-deoxyuridine triphosphate and 2′-deoxycytidine triphosphate and investigated them as substrates for PCRs using Taq, Tth, Vent(exo-), KOD Dash and KOD(exo-) polymerases and pUC 18 plasmid DNA as a template. These assays were performed on two different amplifying regions of pUC18 with different T/C contents that are expected to have relatively high barriers for incorporation of either modified dU or dC. On the basis of 260 different assays (26 modified triphosphates × 5 DNA polymerases × 2 amplifying regions), it appears that generation of the full-length PCR product depends not only on the chemical structures of the substitution and the nature of the polymerase but also on whether the substitution is on dU or dC. Furthermore, the template sequence greatly affected generation of the PCR product, depending on the combination of the DNA polymerase and modified triphosphate. By examining primer extension reactions using primers and templates containing C5-modified dUs, we found that a modified dU at the 3′ end of the elongation strand greatly affects the catalytic efficiency of DNA polymerases, whereas a modified dU opposite the elongation site on the template strand has less of an influence on the catalytic efficiency.