The relationships between fear of cancer recurrence, spiritual well-being and psychological resilience in non-metastatic breast cancer survivors during the COVID-19 outbreak.

OBJECTIVES: This study examines the relationships between fear of cancer recurrence (FCR), spiritual well-being (SWB) and psychological resilience in breast cancer survivors during the COVID-19 outbreak, and investigates to what extent breast cancer survivors' sociodemographic characteristics affect FCR, SWB and psychological resilience levels. METHODS: The study was conducted at Canakkale University Hospital in Turkey. Included in the study were 82 non-metastatic breast cancer patients whose clinical outcomes were followed-up after primary treatment, but suspended due to the COVID-19 outbreak. FCR, SWB and psychological resilience were assessed using the FCR inventory-short form (FCRI-SF), SWB scale and the brief resilience scale (BRS), respectively. RESULTS: The mean scores of breast cancer survivors concerning FCR, SWB, and psychological resilience were 17.77 ± 5.38, 36.20 ± 6.21 and 20.01 ± 4.51, respectively. A significant negative correlation was noted between the scores of FCR and SWB and psychological resilience (r = -0.329, p < 0.001 and r = -0.316, p = 0.004, respectively). Additionally, a significantly positive correlation was identified between psychological resilience and SWB (r = 0.501, p = 0.003). A hierarchical linear regression analysis with FCRI-SF as the dependent variable, and SWB and BRS as explanatory variables, indicated that SWB affects FCRI-SF scores and is a potential predictor of FCR. A mediation analysis revealed that SWB partially mediated the relationship between psychological resilience and FCR. CONCLUSION: Breast cancer survivors with high SWB and psychological resilience scores experience less FCR, despite their failure to maintain the medical follow-up due to the COVID-19 outbreak. Efforts should be made to increase the psychological resilience and SWB of patients diagnosed with breast cancer.

Aurora A overexpression in breast cancer patients induces taxane resistance and results in worse prognosis.

PURPOSE: The aim of this study was to determine the expression level of Aurora A in human breast cancer tissues and to test whether there is a relationship between its expression levels and clinicopathological parameters including response to taxanes, tumor grade, estrogen receptor (ER) status, human epidermal growth factor receptor 2 (HER2) status, and overall survival (OS). METHODS: We retrospectively analyzed paraffin-embedded tissue sections from 49 metastatic breast cancer patients whose clinical outcomes had been tracked after taxane treatment. The expression status of Aurora A was defined by immunohistochemistry (IHC) using the anti-Aurora A antibody. RESULTS: Aurora A was overexpressed in 73% of the examined specimens. There was significant correlation between high Aurora A expression and decreased taxane sensitivity (p=0.02). There was no association between the clinicopathological parameters including histologic grade, ER positivity and triple negative molecular subtype and the level of Aurora A expression. However, HER2 positive tumors showed significantly higher Aurora A expression compared with HER2 negative tumors (p=0.02). Kaplan-Meier survival analysis failed to show a significant correlation between expression levels of Aurora A and OS although patients with low Aurora A levels had a marginally longer survival compared to patients with high levels. CONCLUSION: Our data suggest that Aurora A may be a promising predictive and prognostic marker in patients with breast cancer.

Zoledronic acid in combination with serine/threonine phosphatase inhibitors induces enhanced cytotoxicity and apoptosis in hormone-refractory prostate cancer cell lines by decreasing the activities of PP1 and PP2A.

UNLABELLED: What's known on the subject? and What does the study add? Prostate cancer is the second most common cancer diagnosed among elderly men. Current standard of care with surgery, chemotherapy or radiation in prostate cancer patients are of limited efficacy, especially in the androgen refractory state of the disease, and unfortunately metastatic disease remains incurable. Skeletal metastases are the most common site for metastases for prostate cancer and bisphosphonates have been widely used for the treatment of morbidity due to skeletal related events. Zoledronic acid (ZA) is the most potent member of the nitrogen containing new generation bisphosphonate (N-BPs) family. Okadaic acid (OA) and Calyculin A (CA) are the most commonly used inhibitors of PP1 and 2A. OA, extracted from common black sponge Halachondria okaddai is a potent inhibitor of protein phosphatases, PP1 and PP2A, and CA was isolated from another marine sponge, Discodermia calyx. Therapies based on combinations of chemotherapeutics with phosphatase inhibitors that target signaling pathways within the cell with different mechanisms of action, may be useful for increasing therapeutic effect and also diminish toxic side effects by decreasing the doses of conventional chemotherapeutics. Although clinically well known, the in vitro effects of ZA on cancer cells and the underlying mechanisms are not well elucidated. In our previous studies, we have already shown anticancer effect of ZA in hormone-and drug refractory prostate cancer cells, PC-3 and DU-145. In addition to this, we have also shown that this anticancer effect may be augmented with some cytotoxic agents in prostate cancer. Now, in our present study, we have investigated whether ZA induced growth inhibition and apoptosis in PC-3 and DU-145 may be enhanced by the combination with CA or OA, through inhibition of serine/threonine phosphatases in prostate cancer cells. Both ZA/CA and ZA/OA combinations inhibited the cell viability of hormone-and drug refractory prostate cancer cells at in vivo achievable therapeutic concentrations. Moreover, a potentiation of the apoptotic effects of the combinations was also observed in the same experimental conditions. This is the first report of a synergistic combination of ZA with phosphatase inhibitors CA and OA which inhibits cell viability and induces apoptosis in human hormone and drug refractory prostate cancer cells. OBJECTIVES: • To investigate if the cytotoxic and apoptotic effect of zoledronic acid (ZA) can be enhanced by the addition of the serine/threonine protein phosphatase inhibitors calyculin A (CA) and okadaic acid (OA) in hormone and drug refractory prostate cancer cells, PC-3 and DU-145. • To discover the effect of these combination treatments on phosphatase 1 (PP1) and PP2A protein expression levels in prostate cancer cells. MATERIALS AND METHODS: • An XTT cell viability assay was used to determine cytotoxicity. • Apoptosis was evaluated by enzyme-linked immunosorbent assay (ELISA) using a Cell Death Detection ELISA Plus Kit and verified by measuring caspase 3/7 enzyme activity. • The PP1 and PP2A enzyme activities were evaluated by serine/threonine phosphatase ELISA and expression levels of PP1 and PP2A proteins were then re-assessed by Western blot analysis. RESULTS: • Combination of ZA with either CA or OA showed synergistic cytotoxicity and apoptosis compared with any agent alone in both PC-3 and DU-145 prostate cancer cells. • The combination of ZA with phosphatase inhibitors resulted in enhanced suppression of both PP1 and PP2A enzyme activity and protein levels, which was more overt with the ZA/CA combination. CONCLUSION: • Results from our study increase the translational potential of our in vitro findings and offer the basic rationale for the design of new combinatory strategies with ZA and phosphatase inhibitors for the treatment of prostate cancer, which may become resistant to conventional therapy.

Predictive and Prognostic Role of Lipocalin-2 Expression in Prostate Cancer and Its Association with Gleason Score.

Lipocalin-2 has an important role in tumor progression, invasion, and metastasis. However, its role in prostate cancer remains unclear. The objective of this study is to determine the expression level of lipocalin-2 in human prostate cancer tissues and to evaluate the relationship between its expression level and clinicopathologic parameters including response to docetaxel treatment, Gleason score, progression-free survival (PFS), and overall survival (OS). We retrospectively analyzed paraffin-embedded tissue sections from 33 metastatic castrate-resistant prostate cancer (mCRPC) patients whose clinical outcomes had been tracked after docetaxel treatment. The expression status of lipocalin-2 was defined by immunohistochemistry (IHC) using the anti-lipocalin-2 antibody. Lipocalin-2 was highly expressed in 36% of the examined specimens. There was no significant correlation between high lipocalin-2 expression and docetaxel response (p : 0.09). High lipocalin-2 expression was significantly associated with a higher Gleason score (p=0.027). Kaplan-Meier survival analysis failed to show a significant correlation between expression levels of lipocalin-2 and both OS and PFS although patients with high lipocalin-2 levels had a numerically shorter PFS and OS time compared to patients with low levels. Consequently, it is clear that further studies are needed to evaluate the predictive and prognostic role of lipocalin-2 in prostate cancer patients.

Hormone receptor status and survival of medullary breast cancer patients. A Turkish cohort.

OBJECTIVES: To analyze the relationship between clinical features, hormonal receptor status, and survival in patients who were diagnosed with medullary breast cancer (MBC). Methods: Demographic characteristics, histopathological features, and survival statuses of 201 patients diagnosed with MBC between 1995 and 2015 were retrospectively recorded. Survival analyses were conducted with uni- and multivariate cox regression analysis. RESULTS: Median follow-up time was 54 (4-272) months. Median patient age at the time of diagnosis was 47 years old (26-90). Of the patients, 91.5% were triple negative. Five-year recurrence free survival time (RFS) rate was 87.4% and overalll survival (OS) rate 95.7%. For RFS, progesterone receptor (PR) negativity, atypical histopathological evaluation, absence of lymphovascular invasion, smaller tumor, lower nodal involvement were found to be favourable prognostic factors by univariate analysis (p less than 0.05). The PR negativity and smaller tumor were found to be favourable factors by univariate analysis (p less than 0.05). However, none of these factors were determined as significant independent prognostic factors for OS (p greater than 0.05).  Conclusion: Turkish MBC patients exhibited good prognosis, which was comparable with survival outcomes achieved in the literature. The PR negativity was related to a better RFS and OS rates.

Predictive and prognostic values of BubR1 and synuclein-gamma expression in breast cancer.

The aim of this study is to determine the expression level of spindle assembly checkpoint (SAC) proteins-BubR1 and synuclein-gamma (SNCG) in human breast cancer tissues and to test whether there is a relationship between their expression levels and clinicopathologic parameters including respons to taxanes, tumor grade, estrogen receptor (ER) pozitivity, HER2 status, and overall survival (OS). We analyzed retrospectively paraffin-embedded tissue sections from 55 breast cancer patients whose clinical outcomes had been tracked after taxane treatment in neoadjuvan and metastatic setting. The expression status of BubR1 and SNCG was defined by immunohistochemistry (IHC) using the anti-BubR1 and anti-SNCG antibody. The BubR1 and SNCG was overexpressed in 38% and 62% of the study group, respectively. There was borderline significant correlation between low BubR1 expression and increased taxane sensitivity (P=0.05). In contrast, high SNCG expression was significantly associated with decreased taxane sensitivity (P=0.01). There was no association between the clinicopathologic parameters including histologic grade, ER positivity and HER2 status and the level of these proteins. However, triple negative tumors showed significantly more high BubR1 expression than those other molecular subtypes (P=0.04). Kaplan-Meier survival analysis failed to show a significant correlation between expression levels of BubR1 and SNCG and overall survival although patients with low levels of both proteins had a marginally longer survival time compared to those with high levels. In summary, our data suggest that both BubR1 and SNCG may be promising predictive marker rather than prognostic marker in patients with breast cancer.

Predictive and prognostic values of Tau and BubR1 protein in prostate cancer and their relationship to the Gleason score.

The aim of this study is to detect the expression levels of spindle assembly checkpoint protein-BubR1 and microtubule-associated protein-Tau in human prostate cancer tissues of different Gleason score, and to test whether there is a relationship between their expression levels and clinicopathologic parameters including response to docetaxel treatment, Gleason score, and overall survival (OS). Moreover, to test whether Tau protein expressed in the cancerous prostate tissue is phosphorylated. Thirty patients who received at least three cycles docetaxel for metastatic castrate-resistant prostate cancer were included into the trial. The patients' formalin-fixed and paraffin-embedded prostate tissue specimens were retrospectively obtained from the pathology department archives of Ege University School of Medicine. The expression status of BubR1 protein was defined by immunohistochemical (IHC) using the anti-BubR1 antibody. The expression status of Tau protein was defined by IHC using the two types of Tau antibodies: anti-Tau-1 antibody (that recognizes Tau only in its dephosphorylated form) and anti-PHF-Tau antibody (that recognizes all isoforms of human Tau proteins independent of its phosphorylation status). The BubR1 and Tau were overexpressed in about 63 and 23 % of the study group, respectively. Tau overexpression was significantly associated with lower Gleason score. There was no significant association between the expression levels of BubR1 and Tau proteins, and docetaxel response. Reduced BubR1 expression was strongly associated with longer survival (P = 0.008), whereas Tau expression status did not effect survival. Moreover, the Tau expression of cancerous prostate tissue was highly dephosphorylated. In this clinicopathological study, our findings did not confirm the preclinical observations that low BubR1 and Tau expression confer selective sensitivity to microtubulisin drugs. Our data imply that reduced BubR1 expression was a predictor for longer OS, and the possibility that high Tau expression may be involved in better prognosis due to its relationship to the Gleason score. Furthermore, our data suggest that both Tau and BubR1 may be a promising prognostic marker rather than predictive marker in patients with prostate cancer.

Combined gossypol and zoledronic acid treatment results in synergistic induction of cell death and regulates angiogenic molecules in ovarian cancer cells.

In the present study, we aimed to evaluate the possible synergistic, cytotoxic effects of combination treatment of gossypol and zoledronic acid, in human ovarian cancer cell lines, OVCAR-3 and MDAH-2774, and to elucidate the role of this novel combination treatment on angiogenesis-related molecules in ovarian cancer. The XTT cell viability assay was used for showing cytotoxicity. Both DNA fragmentation by ELISA assay and caspase 3/7 activity measurement were used for demonstrating apoptosis. To elucidate the angiogenic molecules affected by combination treatment, mRNA levels of angiogenic molecules were measured using the Human Angiogenesis RT2 ProfilerTM PCR Array (SuperArray, Frederick, MD) in ovarian cancer cell lines, OVCAR-3 and MDAH-2774.The combined treatment resulted in significant, synergistic cytotoxicity, and induced apoptosis. This effect was observed to happen in a dose- and time-dependent manner. Moreover, the combination treatment of 10 microM gossypol and 5 microM zoledronic acid resulted in significant down-regulation (>or= thee-fold) in mRNA levels of some pivotal angiogenic molecules in OVCAR-3 and MDAH-2774 cells as compared to the untreated control. However, this effect was different in the two ovarian cancer cell lines observed. Gossypol, in combination with zoledronic acid, may provide a rational treatment option for ovarian cancer, not only by direct inhibition of cell proliferation, but also inhibition of angiogenesis-related molecules.