Update Knowledge Assessment and Influencing Predictor of Female Fertility Preservation in Oncologists.

OBJECTIVE: This study aims to offer an update assessment of the knowledge of Chinese oncologists on female fertility preservation, and identify the determinants that influence the implementation of fertility preservation. METHODS: A total of 713 Chinese oncologists with different specialties completed the online self-report questionnaire to assess their understanding of fertility risks in cancer treatment, knowledge on female fertility preservation, and perceptions on the barriers in referring patients for fertility preservation. RESULTS: Although most oncologists were familiar with fertility risk in cancer treatment, half of them lacked the knowledge for reproduction and preservation methods. In the multivariable model, oncologists in a hospital with a specialized reproductive institution, positive precaution for fertility risk, and fertility preservation discussion with patients were significantly correlated with the possibility of fertility preservation referral. CONCLUSIONS: The intervention targets based on the update evaluation and identified influencing determinants will be helpful for all the oncofertility researchers, oncologists and institutions in future efforts for well-established female fertility preservation services.

Gel-based chemical cross-linking analysis of 20S proteasome subunit-subunit interactions in breast cancer.

The ubiquitin-proteasome system plays a pivotal role in breast tumorigenesis by controlling transcription factors, thus promoting cell cycle growth, and degradation of tumor suppressor proteins. However, breast cancer patients have failed to benefit from proteasome inhibitor treatment partially due to proteasome heterogeneity, which is poorly understood in malignant breast neoplasm. Chemical crosslinking is an increasingly important tool for mapping protein three-dimensional structures and proteinprotein interactions. In the present study, two cross-linkers, bis (sulfosuccinimidyl) suberate (BS(3)) and its water-insoluble analog disuccinimidyl suberate (DSS), were used to map the subunit-subunit interactions in 20S proteasome core particle (CP) from MDA-MB-231 cells. Different types of gel electrophoresis technologies were used. In combination with chemical cross-linking and mass spectrometry, we applied these gel electrophoresis technologies to the study of the noncovalent interactions among 20S proteasome subunits. Firstly, the CP subunit isoforms were profiled. Subsequently, using native/SDSPAGE, it was observed that 0.5 mmol/L BS(3) was a relatively optimal cross-linking concentration for CP subunit-subunit interaction study. 2-DE analysis of the cross-linked CP revealed that α1 might preinteract with α2, and α3 might pre-interact with α4. Moreover, there were different subtypes of α1α2 and α3α4 due to proteasome heterogeneity. There was no significant difference in cross-linking pattern for CP subunits between BS(3) and DSS. Taken together, the gel-based characterization in combination with chemical cross-linking could serve as a tool for the study of subunit interactions within a multi-subunit protein complex. The heterogeneity of 20S proteasome subunit observed in breast cancer cells may provide some key information for proteasome inhibition strategy.

Prevalence, intensity, and prognostic significance of common symptoms in terminally ill cancer patients.

BACKGROUND: Quality of life and palliative management of end-stage cancer patients should improve with greater understanding of the prevalence, intensity, and prognostic significance of their symptoms. OBJECTIVE: We investigated the association between prevalence and intensity of common symptoms and overall survival in Chinese end-stage cancer patients. DESIGN: For this cross-sectional study, 163 Chinese patients with end-stage cancer completed an Edmonton Symptom Assessment questionnaire, and each was given a Karnofsky Performance Status (KPS) score. Overall survival was estimated via the Kaplan-Meier method. Factors affecting overall survival were determined by univariate and multivariate Cox regression analyses. RESULTS: Mean survival of these patients was 51 days. Pain, lack of appetite, and poor well-being were the most frequent symptoms, in 90.2%, 88.3%, and 87.7%, respectively. The most severe symptoms were fatigue, lack of appetite, drowsiness, and poor well-being. Fatigue, lack of appetite, drowsiness, shortness of breath, poor well-being, depression, and KPS score significantly affected overall survival rate, with a relative risk of dying of 1.560, 2.320, 1.684, 1.295, 1.912, 1.414, and 0.487, respectively (Cox regression coefficients: 0.361, 0.827, 0.539, 0.185, 0.694, 0.318, and -0.602). Fatigue, lack of appetite, shortness of breath, age, and KPS score were independent risk factors of overall survival, with a relative risk of dying of 1.581, 1.122, 1.123, 1.022, and 0.797, respectively (Cox regression coefficients: 0.458, 0.115, 0.116, 0.022, and -0.227). CONCLUSION: Fatigue, shortness of breath, lack of appetite, age, and KPS score were associated with overall survival of end-stage Chinese cancer patients.

Should few retrieved oocytes be as an indication for intracytoplasmic sperm injection?

OBJECTIVE: To reevaluate whether relatively few oocytes obtained in one cycle are an indication for intracytoplasmic sperm injection (ICSI). METHODS: A total of 406 cycles with three or fewer retrieved oocytes performed in 396 non-male infertile couples were retrospectively reviewed. Cycles were classified into three groups by different fertilization techniques: the in vitro fertilization (IVF) group, insemination with conventional IVF; the ICSI group, insemination with ICSI though semen parameters were normal; and the rescue ICSI group, re-insemination with ICSI after conventional IVF failure. RESULTS: The ICSI group resulted in higher normal fertilization compared with the conventional IVF group. Correspondingly, the cycle cancellation rate was decreased in the ICSI group, though it was not statistically significant. The clinical pregnancy rate and implantation rate were lower in the ICSI group compared with the conventional IVF group. Rescue ICSI was a method to avert total fertilization failure in conventional IVF, increasing fertilization and ensuring embryo availability for transfer, but the normal fertilization was the lowest due to delayed insemination and the chance of pregnancy was very little. CONCLUSIONS: Obtaining only few oocytes in one cycle is not considered as an indication for ICSI when the sperm sample is apparently normal. Rescue ICSI is either not recommended if conventional insemination fails. Such patients should not be subjected to the unnecessary costs and potential risks of ICSI.

MicroRNA-10b targets E-cadherin and modulates breast cancer metastasis.

BACKGROUND: Recent studies have suggested that microRNA-10b (miR-10b) acts as a promoter of metastasis in breast cancer, although the underlying mechanism remains largely unknown. In this study, we provide the first evidence that E-cadherin (E-cad) is a potential target of miR-10b. MATERIAL/METHOD: By applying gain-of-function and loss-of-function approaches in the metastatic breast cancer cell line MDA-MB-231, we demonstrated that miR-10b is necessary and sufficient to regulate the cellular expression of E-cad and in vitro tumor cell invasion. RESULTS: Comparative expression analysis of miR-10b in benign breast lesions (N=16), primary breast cancers (N=21), and metastatic breast carcinomas (N=23) revealed that miR-10b transcription was uniquely up-regulated in metastatic cancers. The expression level of miR-10b positively correlated with tumor size, pathological grading, clinical staging, lymph node metastasis, Her2-positivity and tumor proliferation, but was negatively associated with estrogen receptor-positivity, progesterone receptor-positivity and E-cad mRNA and protein levels. CONCLUSIONS: These findings indicate the existence of a novel E-cadherin-related mechanism by which miR-10b modulates breast cancer metastasis. In addition, miR-10b may be a useful biomarker of advanced progression and metastasis of breast cancer.

Association between symptoms and their severity with survival time in hospitalized patients with far advanced cancer.

OBJECTIVE: To assess the significance of symptoms and their severity for predicting survival of hospitalized patients with far advanced cancer. METHODS: Two hundred fifty-six patients with far advanced cancer at the Cancer Center of Tongji Hospital, China were assessed by the Chinese version of the M.D. Anderson Symptom Inventory (MDASI-C). A Cox regression model was used to determine symptoms that could predict survival time. The log-rank test was used to compare the survival of patients accompanied by significant symptoms at different intensities. RESULTS: Median survival was 49 days. Fatigue was the most common and severe symptom, followed by lack of appetite, disturbed sleep, and pain. Multivariate analysis showed that fatigue, shortness of breath, lack of appetite, and feeling sad were independent prognostic factors for survival time (p < 0.05), with a hazard ratio of dying of 1.39, 1.13, 1.33, and 1.16, respectively. The survival time for patients with different intensities of the four symptoms showed significant differences (p < 0.01). CONCLUSIONS: Fatigue, lack of appetite, feeling sad, and shortness of breath could be predictive factors for survival time of hospitalized patients with far advanced cancer. The more severe these symptoms are, the shorter will be survival time.