In lymphoma patients with resolved HBV infections, chemotherapy-induced HBV reactivation is not uncommon, but can be managed with regular monitoring of HBV DNA and prompt antiviral therapy. Serological breakthrough (i.e., reappearance of HBsAg) is the most important predictor of HBV-related hepatitis flare. (Hepatology 2014;59:2092-2100).

Female invasive breast cancer (FIBC) in Taiwan is characterized by a striking recent increase of incidence and a relatively young median age (45-49 years) at diagnosis. The Westernization of lifestyle that is increasingly affecting younger generations of Taiwanese may have an important impact on this change. We compared epidemiologic data on FIBC in Taiwanese obtained from the Taiwan Cancer Registry with data for Caucasian Americans obtained from the database of the Surveillance, Epidemiology, and End Results Program for the period from 1980 to 1999. Agespecific incidence rates of FIBC were plotted by calendar year at diagnosis and by birth cohort for both populations. The individual effects of time period and birth cohort on the incidence trends of FIBC in both populations were evaluated using the age-period-cohort analysis. The incidence rate of FIBC was continuously increased in Taiwanese throughout the past 2 decades, whereas the increase of incidence was slowing down in Caucasian Americans. The incidence rates in Taiwanese women born after the 1960s were approaching that of Caucasian Americans. The age-period-cohort analysis showed a much stronger birth cohort effect on the incidence trend of FIBC in Taiwanese than in Caucasian Americans. This strong birth cohort effect corresponded to the Westernization of lifestyle in Taiwan since 1960. These findings indicate that a continued shift in the incidence and age distribution pattern of FIBC in Taiwanese toward that of Caucasian Americans should be anticipated. (Cancer Epidemiol Biomarkers Prev 2005;14(8):1986 -90)

Accurately understanding prognosis is associated with fewer preferences for life-sustaining treatments and is correlated with both patient and institutional characteristics. Interventions should be developed to improve accurate prognostic understanding, thus facilitating informed EOL-care decisions that may limit the use of aggressive interventions.

Indole-3-carbinol has emerged as a promising chemopreventive agent due to its in vivo efficacy in various animal models. However, indole-3-carbinol exhibits weak antiproliferative potency and is unstable in acidic milieu. Thus, this study was aimed at exploiting indole-3-carbinol to develop potent antitumor agents with improved chemical stability. This effort culminated in OSU-A9 {[1-(4-chloro-3-nitrobenzenesulfonyl)-1H-indol-3-yl]-methanol}, which is resistant to acid-catalyzed condensation, and exhibits 100-fold higher apoptosis-inducing activity than the parent compound. Relative to indole-3-carbinol, OSU-A9 displays a striking qualitative similarity in its effects on the phosphorylation or expression of multiple signaling targets, including Akt, mitogen-activated protein kinases, Bcl-2 family members, survivin, nuclear factor-KB, cyclin D1, p21, and p27. The ability of OSU-A9 to concurrently modulate this broad range of signaling targets underscores its in vitro and in vivo efficacy in prostate cancer cells. Nevertheless, despite this complex mode of mechanism, normal prostate epithelial cells were less susceptible to the antiproliferative effect of OSU-A9 than PC-3 and LNCaP prostate cancer cells. Treatment of athymic nude mice bearing established s.c. PC-3 xenograft tumors with OSU-A9 at 10 and 25 mg/kg i.p. for 42 days resulted in a 65% and 85%, respectively, suppression of tumor growth. Western blot analysis of representative biomarkers in tumor lysates revealed significant reductions in the intratumoral levels of phosphorylated (p-) Akt, Bcl-xL, and RelA, accompanied by robust increases in p-p38 levels. In conclusion, the ability of OSU-A9 to target multiple aspects of cancer cell survival with high potency suggests its clinical value in prostate cancer therapy. [Cancer Res 2007;67(16):7815-24]

Phenothiazines (PTZs) have been used for the antipsychotic drugs for centuries. However, some of these PTZs have been reported to exhibit antitumor effects by targeting various signaling pathways in vitro and in vivo. Thus, this study was aimed at exploiting trifluoperazine, one of PTZs, to develop potent antitumor agents. This effort culminated in A4 [10-(3-(piperazin-1-yl)propyl)-2-(trifluoromethyl)-10H-phenothiazine] which exhibited multi-fold higher apoptosis-inducing activity than the parent compound in oral cancer cells. Compared to trifluoperazine, A4 demonstrated similar regulation on the phosphorylation or expression of multiple molecular targets including Akt, p38, and ERK. In addition, A4 induced autophagy, as evidenced by increased expression of the autophagy biomarkers LC3B-II and Atg5, and autophagosomes formation. The antitumor activity of A4 also related to production of reactive oxygen species and adenosine monophosphate-activated protein kinase. Importantly, the antitumor utility of A4 was extended in vivo as it, administrated at 10 and 20 mg/kg intraperitoneally, suppressed the growth of Ca922 xenograft tumors. In conclusion, the ability of A4 to target diverse aspects of cancer cell growth suggests its value in oral cancer therapy.

To assess the role of leukapheresis and cranial irradiation in reducing the incidence of intracranial hemorrhage (ICH) and early death in patients with hyperleukocytic acute myeloid leukemia (AML) and the impact of such treatment on survival. This study retrospectively analyzed the records of 75 patients with hyperleukocytic AML who had a white cell count over 100,000/lL. All patients had de novo AML except for two with therapy-related AML. Various factors were assessed for their impact on morbidity and mortality, particularly the role of pre-induction leukapharesis and cranial irradiation. The most significant risk factors for ICH were the presence of two or more symptoms of leukostasis (odds ratios [OR] 10.6, 95% CI: 2.67-42.02; P 5 0.001) and respiratory distress (OR 5.41, 95% CI: 1.44-20.32, P 5 0.012). The most significant risk factors for early death were age ‡ 65 (OR 4.21, 95% CI: 1.45-12.21, P 5 0.008), respiratory failure (OR 3.34, 95% CI: 1.24-9.50, P 5 0.018), and two or more symptoms (OR 3.50 95% CI: 1.16-10.52, P 5 0.026). Neither leukapheresis nor cranial irradiation were significantly associated with a decreased incidence of ICH (P 5 0.349 and 0.378, respectively). Leukapheresis had no significant influence on early death (P 5 0.367). The median survival patients receiving no pretreatment was 10.50 months (range 2.58-18.42) and for those receiving pretreatment 1.50 months (range 0.10-3.16; log-rank test, P 5 0.062). Leukapheresis and cranial irradiation do not improve survival or decrease the incidence of ICH in adults with hyperleukocytic AML. Am. J. Hematol. 82:976-980, 2007. V

Conventional cytogenetics can categorize patients with acute myeloid leukemia (AML) into favorable, intermediate, and unfavorable-risk groups; however, patients with intermediate-risk cytogenetics represent the major population with variable outcomes. Because molecular profiling can assist with AML prognosis and next-generation sequencing allows simultaneous sequencing of many target genes, we analyzed 260 genes in 112 patients with de novo AML who received standard treatment. Multivariate analysis showed that karyotypes and mutation status of TET2, PHF6, KIT, and NPM1 mutation /FLT3-internal tandem duplication (ITD) negative were independent prognostic factors for the entire cohort. Among patients with intermediate-risk cytogenetics, patients with mutations in CEBPA double mutation , IDH2, and NPM1 in the absence of FLT3-ITD were associated with improved Overall survival (OS), similar to those with favorable-risk cytogenetics; patients with mutations in TET2, RUNX1, ASXL1, and DNMT3A were associated with reduced OS, similar to those with unfavorable-risk cytogenetics. We concluded that integration of cytogenetic and molecular profiling improves prognostic stratification of patients into three groups with more distinct prognoses (P < 0.001) and significantly reduces the number of patients classified as intermediate risk. In addition, our study demonstrates that next-generation sequencing (NGS)-based multi-gene sequencing is clinically applicable in establishing an accurate risk stratification system for guiding therapeutic decisions. Cancer Medicine Open Access 350

Abstract. The DNA repair gene X-ray cross-complementing group 4 (XRCC4), a member of the non-homologous endjoining (NHEJ) repair system, plays a major role in the repair of the double-strand breaks of the DNA sequence. This gene is critical to the maintenance of overall genome stability, and is also thought to play a key role in human carcinogenesis. In this case-control study, several novel polymorphic variants of XRCC4, including C-1622T (rs7727691), G-1394T (rs6869366), C-571T (rs2075686) and intron3 DIP (rs28360071), were investigated, and the correlation of these variants to prostate cancer susceptibility in a Taiwanese population was observed. A total of 134 prostate cancer patients were recruited along with 134 age-matched healthy controls, and the association of their selected genotypes with susceptibility to prostate cancer was determined. The G-1394T variant of XRCC4 proved, after analysis of the frequencies of each variant in the prostate cancer and control groups, to be a significant single nucleotide polymorphism (SNP) in prostate carcinogenesis. Our data clearly indicate