Correction: All-purpose nanostrategy based on dose deposition enhancement, cell cycle arrest, DNA damage, and ROS production as prostate cancer radiosensitizer for potential clinical translation.

Correction for 'All-purpose nanostrategy based on dose deposition enhancement, cell cycle arrest, DNA damage, and ROS production as prostate cancer radiosensitizer for potential clinical translation' by Xiao-xiao Guo et al., Nanoscale, 2021, 13, 14525-14537, https://doi.org/10.1039/D1NR03869A.

All-purpose nanostrategy based on dose deposition enhancement, cell cycle arrest, DNA damage, and ROS production as prostate cancer radiosensitizer for potential clinical translation.

Radiotherapy (RT) is one of the main treatments for men with prostate cancer (PCa). To date, numerous sophisticated nano-formulations as radiosensitizers have been synthesized with inspiring therapeutic effects both in vitro and in vivo; however, almost all the attention has been paid on the enhanced dose deposition effect by secondary electrons of nanomaterials with high atomic numbers (Z); despite this, cell-cycle arrest, DNA damage, and also reactive oxygen species (ROS) production are critical working mechanisms that account for radiosensitization. Herein, an 'all-purpose' nanostrategy based on dose deposition enhancement, cell cycle arrest, and ROS production as prostate cancer radiosensitizer for potential clinical translation was proposed. The rather simple structure of docetaxel-loaded Au nanoparticles (NPs) with prostate specific membrane antigen (PSMA) ligand conjugation have been successfully synthesized. Enhanced cellular uptake achieved via the selective internalization of the NPs by PCa cells with positive PSMA expression could guarantee enhanced dose deposition. Moreover, the as-synthesized nanosystem could effectively arrest the cell cycle at G2/M phases, which would reduce the ability of DNA damage repair for more irradiation sensitive of the PCa cells. Moreover, the G2/M phase arrest would further promote cascade retention and the enrichment of NPs within the cells. Furthermore, ROS generation and double strand breaks greatly promoted by NPs under irradiation (IR) could also provide an underlying basis for effective radiosensitizers. In vitro and in vivo investigations confirmed the as-synthesized NPs as an effective nano-radiosensitizer with ideal safety. More importantly, all moieties within the present nanosystem have been approved by FDA for the purpose of PCa treatment, thus making it highly attractive for clinical translation.

Bisindole alkaloids from Tabernaemontana corymbosa.

Continued study in bioactive monoterpenoid alkaloids led to the isolation of nine undescribed alkaloids, taberyunines A-I, together with 32 known ones from the aerial parts of Tabernaemontana corymbosa Roxb. ex Wall (Apocynaceae). Among the undescribed alkaloids, taberyunines A-G and H-I were assigned to Aspidosperma-Aspidosperma and Vobasinyl-Ibogan type bisindoles, respectively. Their structures were determined by NMR spectra, MS data and X-ray diffraction. Taberyunine B showed significant cytotoxicity against three cancer cell lines.

Adjuvant therapy of breast cancer with pirarubicin versus epirubicin in combination with cyclophosphamide and 5-fluorouracil.

We performed a retrospective study of 856 breast cancer patients in our hospital, to compare the therapeutic effect of pirarubicin with cyclophosphamide and 5-fluorouracil (CPF) with the standard epirubicin-based regimen (CEF) in adjuvant treatment of breast cancer. Patients were given cyclophosphamide and 5-fluorouracil 500 mg/m(2) each, and either pirarubicin 40 mg/m(2) or epirubicin 75-100 mg/m(2) , every 3 weeks, six cycles. A total of 233 patients used CPF and 623 patients used CEF regimen. The clinical and pathologic characteristics were well balanced between the two groups. The median follow-up time was 41 months, relapse-free survival (RFS) and overall survival (OS) were similar in both groups, p = 0.561 and p = 0.783, respectively. No treatment-related congestive heart failure or death was observed in either group. Regardless of chemotherapy regimens, only tumor size, lymph node status, and ER status were predictive factors in multivariate survival analysis. In stratified analysis, the total hazard ratio estimate for RFS was 0.876 (95% CI 0.561-1.369; p = 0.562), not in favor of either regimen, and no significant difference was observed in any subgroups between the two treatment arms. Our study verified that 3 weekly CPF gives the same efficacy and safety as the standard CEF; both CPF and CEF are the effective regimens that can be used in adjuvant chemotherapy of breast cancer.

[Retrospective analysis of trastuzumab treatment in 141 patients with Her-2 positive breast cancer].

OBJECTIVE: To summarize the clinical experience of trastuzumab treatment in neoadjuvant, adjuvant, metastatic setting of Chinese patients with Her-2 positive breast cancer and evaluate the efficacy of trastuzumab in combination with chemotherapy. METHODS: From January 2004 to December 2008, 141 outpatients with breast cancer treated with trastuzumab were investigated retrospectively. The follow-up time ranged from 3 to 319 months. The disease free survival time (DFS) of metastatic setting was calculated. The overall survival time (OS), time to treatment failure (TTF) and clinical response rate (CRR, including complete response, partial response and stable disease) of adjuvant, first-line, second-line therapy were analyzed statistically. RESULTS: In the neoadjuvant regimen, paclitaxel plus carboplatin in combination with trastuzumab accounted for 66.7%, which achieved pathological complete response in 10 of 16 patients. In the adjuvant regimen, anthracycline or anthracycline followed by taxane accounted for 53.9%. The median DFS of 57 cases with metastatic diseases was 17 months. The CRR of first-line trastuzumab use in metastatic setting was 84.5%, compared with 44.4% of second-line use. The median TTF of first-line treatment was 24 months compared with 5 months of second-line treatment. Statistically significant differences were observed. CONCLUSION: The regimen of paclitaxel plus carboplatin in combination with trastuzumab deserves wide clinical use. In metastatic setting, first-line treatment of trastuzumab plus chemotherapy can achieve a higher response rate than second-line treatment. Continued trastuzumab therapy combined with different chemotherapy treatment after disease progression may obtain additive clinical advantage.

Fiberoptic ductoscopy combined with cytology testing in the patients of spontaneous nipple discharge.

Fiberoptic ductoscopy system (FDS) offers a safe alternative to ductography in diagnosing intraductal lesions and serves as a guide for subsequent surgery in women with nipple discharge. In this article, we reported the outcomes of FDS combined with cytology testing for diagnosis of spontaneous nipple discharge. From 1997 to 2005, 1,048 women (1,093 breasts total) in the outpatient department underwent successful diagnostic FDS. Discharge was unilateral (86.8%), single ductal (93.4%), and serous (57.9%) or bloody (36.0%). Among 437 (40.0%) of the FDS-positive breasts, we revealed 49 (11.2%) breast carcinomas, 228 (52.2%) central papillomas, and 5 (1.1%) cases of atypical ductal hyperplasia. Ten patients with positive cytology testing received microdochectomy in spite of having a negative FDS, which revealed two additional ductal carcinomas in situ (DCIS), and four papillomas. About 489 breasts were negative for both FDS and cytology testing and were subjected to follow up. About 77 (15.7%) of the breasts underwent tissue diagnosis within a median follow-up time span of 19 months, and one DCIS was detected. The sensitivity of FDS for detection of malignant lesions was 94.2% and increased to 98.1% when combined with cytology testing. Nevertheless, it was less sensitive (p<0.01) if we used cytology testing only (58.3%), mammography (48.6%), high-frequency sonography (36.4%), or combination of mammography and sonography (56.8%) to detect these malignant lesions. These data confirmed the value of FDS combined with cytology testing as a diagnostic procedure in women with nipple discharge.

A multigenic study on breast cancer risk associated with genetic polymorphisms of ER Alpha, COMT and CYP19 gene in BRCA1/BRCA2 negative Shanghai women with early onset breast cancer or affected relatives.

High penetrance genes such as BRCA1 or BRCA2 account for only a small proportion of familial breast cancer in Chinese population. Estrogen has been proposed to participate in the proliferation and carcinogenesis of breast cancer. To investigate the association between genetic polymorphisms in genes encoding estrogen metabolizing, estrogen biosynthesizing enzyme and estrogen receptor and the breast cancer risk in BRCA1/BRCA2 negative Shanghai women, we conducted a case-control study including 114 cases with early-onset breast cancer or affected relatives and 121 healthy controls. The genotypes of estrogen receptor alpha (ERalpha), aromatase (CYP19), and catechol-O-methyltransferase (COMT) genes were analyzed by direct DNA-sequencing. Compared with H/H genotype of COMT Val158Met, COMT Val158Met L/L genotype was associated with a nonsignificantly elevated risk of breast cancer (OR: 3.72; 95% CI: 0.99-13.96, P=0.051). There was no statistically significant difference in genotype frequency of the ERalpha PvuII, ERalpha XbaI and CYP19 Arg264Cys polymorphism between controls and cases. When stratified by menopausal status, COMT Val158Met L/L (OR: 11.94; 95% CI: 1.48-96.03, P=0.02) and ERalpha PvuII P/p genotypes (OR: 2.67; 95% CI: 1.01-7.05, P=0.048) were associated with a significantly elevated risk of breast cancer in premenopausal women, and there was a association between ERalpha XbaI x/x genotype and the nonsignificantly increased risk of breast cancer in premenopausal women (OR: 6.88; 95% CI: 0.80-59.15, P=0.079). The multigenic analysis showed maybe these high risk genotypes had combined effect on breast cancer risk. Our findings suggest that polymorphism of genes involving estrogen-metabolizing pathway, estrogen- biosynthesizing pathway and estrogen receptor pathway may play an important role in the etiology of BRCA1/2 negative breast cancer with hereditary predisposing factors.

Breast conservative therapy in east part of China: a retrospective cohort study.

PURPOSE: To compare the effects of breast conservative therapy (BCT) with modified radical mastectomy (MRM) in women with early stage breast cancer in the east part of China. We conducted a matched retrospective cohort study using data on patients derived from a prospectively collected breast cancer database. METHODS: We used the database that included patients who received MRM or BCT from 1995 to 2002 in our hospital. The match was conducted according to four variables: age at diagnosis, axillary lymph node status, hormone receptor status, and the dimension of tumor. The match ratio was 1:2. MRM group were patients who received MRM treatment (n=254). BCT group were patients who received BCT treatment (n=127). Median follow-up time for the BCT group and MRM group were 58 and 49 months, respectively. The differences of incidence of loco-regional recurrence, disease free survival, and overall survival at 5 years were compared. RESULTS: There were no significant differences in incidence of loco-regional recurrence, DFS and OS at 5 years between the two groups of patients. The incidence of loco-regional recurrence was 1.84% in MRM group and 3.39% in BCT group (P=0.55). The DFS in MRM and BCT patients were 91.57 and 86.04% (P=0.37); the OS in MRM and BCT patient were 97.57 and 96.73% (P=0.66). CONCLUSIONS: For appropriate breast cancer patients, classic lumpectomy plus axillary dissection and postoperative radiotherapy lead to excellent local control and good survival rate in our study. The BCT can result in the same effects as MRM in Chinese breast cancer patients with better cosmetic appearances.

Addition of adjuvant tamoxifen to cyclophosphamide, methotrexate and 5-fluorouracil for premenopausal women with oestrogen receptor-positive breast cancer.

OBJECTIVE: To study the value of adjuvant tamoxifen (TAM) in premenopausal women with oestrogen receptor (ER)-positive breast cancer who received adjuvant cyclophosphamide, methotrexate and 5-fluorouracil (CMF) polychemotherapy. METHODS: Four hundred and two premenopausal ER-positive breast cancer patients who received CMF chemotherapy between January 1990 and December 1999 were retrospectively studied. Disease-free survival (DFS) and overall survival (OS) were used to evaluate the clinical value of TAM therapy. The relationships between nodal status and TAM were also analysed. RESULTS: After a mean of 41 months of follow-up, 43 (13.7%) patients died of breast cancer and 68 (19.9%) patients suffered recurrence. There was a significant difference between TAM and non-TAM treatment groups for DFS (p=0.0058), but no significant difference for OS. For node-negative patients, there was no significant difference between the TAM and non-TAM treatment groups for either DFS or OS. For node-positive patients, the difference between TAM and non-TAM treatment groups was significant for both DFS and OS (p=0.0497 and p=0.0285, respectively). CONCLUSION: TAM resulted in additional benefit to premenopausal patients with node-positive ER-positive breast cancer who received the CMF polychemotherapy regimen.

Induction of apoptosis in retinoid-refractory acute myelogenous leukemia by a novel AHPN analog.

Acute myelogenous leukemia (AML) is a heterogeneous disease consisting of a variety of different leukemic subtypes. While acute promyelocytic leukemia displays marked sensitivity to the differentiating effects of trans-retinoic acid (tRA), other subtypes of AML display resistance. We now describe a novel compound (E)-4-[3-(1-adamantyl)-4-hydroxyphenyl]-3-chlorocinnamic acid (3-Cl-AHPC/MM002) that induces apoptosis in the tRA-resistant leukemia cell lines M07e, KG-1, and HL-60R, and in tRA-resistant patient leukemic blasts. The 3-Cl-AHPC totally inhibits leukemia colony formation at concentrations that inhibit committed human bone marrow stem cell proliferation, that is, granulocyte/macrophage colony-forming units (CFU-GMs) by only 30%. Exposure to 3-Cl-AHPC results in caspase activation and the cleavage of poly(adenosine diphosphate) (poly(ADP)) ribose polymerase. While activation of the extracellular signal-regulated kinase (ERK) and p38 pathways is not necessary for 3-Cl-AHPC-mediated apoptosis, maximal apoptosis requires c-Jun N-terminal kinase (JNK) activation. The 3-Cl-AHPC-mediated cleavage of the antiapoptotic B-cell leukemia XL (Bcl-XL) protein to a proapoptotic 18-kDa product is found in both the M07e cell line and patient leukemic blasts. The 3-Cl-AHPC treatment of mice bearing the AML 1498 cell line results in a 3.3-log kill in the leukemic blasts. While 3-Cl-AHPC does not activate retinoic nuclear receptors, it is a potent inducer of apoptosis in AML cells and may represent a novel therapy in the treatment of this disease.

The analysis of BRCA1 mutations in eastern Chinese patients with early onset breast cancer and affected relatives.

To study the BRCA1 mutations in eastern Chinese patients with early onset breast cancer and affected relatives, 41 patients' genomic DNA from peripheral mononuclear blood cells was studied by using single strand conformational polymorphism (SSCP) and DNA sequencing. The BRCA1 mutations were detected in the whole gene sequence. Three novel disease-causing mutations (c.582C>T, c.735C>T and c.2790delT) occurred in all the patients. Two occurred in the patients younger than 35 years old (9.1%) and one in the patients with affected relatives (5%). Additional sequence variants identified included a novel missense mutation of unknown significance and six polymorphisms. The prevalence of BRCA1 mutations in Chinese patients in Shanghai with early onset breast cancer is similar to that observed in western women, but the incidence of mutations in breast cancer patients in Shanghai with affected relatives isn't as high as that in western women.

Significance of Apoptosis and Apoptotic-Related Proteins, Bcl-2, and Bax in Primary Breast Cancer.

Apoptosis and expression of apoptosis-regulating proteins, Bcl-2 and Bax, have been observed in human breast carcinomas. The authors investigated whether expression of Bcl-2 and Bax proteins and apoptotic index (AI) had significance in cases of primary breast cancer. The authors evaluated Bcl-2 and Bax immunoreactivity and AI in primary breast cancers with the ApopTag method in 91 breast cancer patients retrospectively with long-term follow-up (median 60 months). Bcl-2 expression was seen in 60 (65.9%) cases and Bax expression was observed in 59 (64.8%) cases. Increased Bcl-2 and absence or low Bax immunoreactivity were significantly associated with low AI, high tumor grade, axillary lymph node involvement, postoperative recurrence, and metastasis. Thirty-five (38.5%) samples expressed high AI, which correlated with low tumor grade, absent axillary lymph node metastasis, and low levels of Bcl-2 with Bax overexpression. In univariate analysis, the variables associated with short relapse-free survival (RFS) and overall survival (OS) were large tumor size, axillary lymph node involvement, high histologic grade, low AI, high Bcl-2 expression, and absence or low Bax expression. In multivariate analysis, only Bcl-2 expression, lymph node status, and histologic grade were of independent prognostic value with respect to RFS and OS. Because the vast majority of the patients in this study received chemotherapy, it can be concluded that these apoptotic markers were also predictive of response to chemotherapy. Immunostaining of apoptosis-related genes, Bcl-2 and Bax, together with AI, may stratify high- versus low-risk breast cancer patients.