Breast cancer is the most common form of cancerous disease worldwide. Its treatment leads to a variety of physiological and psychological side effects. This review investigates the question of how ...mindfulness-based stress reduction (MBSR), a stress management program, can influence the quality of life, anxiety, and depression of women diagnosed with breast cancer.
A systematic literature search was conducted in PubMed/MEDLINE and Cochrane Library. Screening by title, abstract and full text was performed, whereby only those articles were included that fit the inclusion criteria. A risk of bias assessment was performed for each included study.
Overall, six studies were included, but not every study investigated all three outcomes. Two studies found positive impacts on quality of life, whereas three did not find a positive correlation between the intervention and quality of life. Four out of six studies found a positive relation between MBSR and anxiety scores, but only half of the included studies found positive results for the interaction between MBSR and depression scores.
Published data suggest that anxiety can be positively influenced by MBSR, which can be used to improve the psychological care of breast cancer patients, both during and after treatment. However, further studies with larger patient numbers and longer observation periods should be conducted in order to elucidate the full potential of MSBR on important areas such as depression and quality of life.
Therapeutic strategies with immune checkpoint inhibitors (ICIs) counteract the immunosuppressive effects of programmed cell death protein-1 (PD-1) and ligand-1 (PD-L1). ICI treatment has emerged in ...first- and second-line therapy of non-small cell lung cancer (NSCLC). As immunotherapeutic treatment with ICIs is a dynamic field where new drugs and combinations are constantly evaluated, we conducted an up-to-date systematic review on comparative efficacy and safety in patients with advanced NSCLC.
We searched PubMed up to February 2020 and Embase, CENTRAL, and clinical trial registries up to August 2018. Additionally, we checked reference lists. We dually screened titles, abstracts and, subsequently, full-texts for eligibility. Two reviewers assessed the risk of bias and graded the certainty of evidence following GRADE (Grading of Recommendations Assessment, Development and Evaluation). For second-line therapy, we performed random-effects meta-analyses. Due to considerable clinical heterogeneity, we reported first-line results narratively.
Of 1497 references, we identified 22 relevant publications of 16 studies. For first-line therapy, a combination of an ICI with chemotherapy improved progression-free survival and overall survival compared to chemotherapy but increased the risk of serious adverse events. Single-agent pembrolizumab increased overall and progression-free survival in patients with PD-L1 expression of ≥50% and resulted in less TRAE than chemotherapy. Compared to placebo, maintenance therapy with durvalumab increased overall and progression-free survival at the downside of higher risk of TRAE. For second-line therapy, a random-effects meta-analysis yielded a statistically significantly improved overall survival (OS) and progression-free survival (PFS) for ICIs compared to docetaxel (HR 0.69; 95% CI: 0.63-0.75 for OS; HR 0.85; 95% CI: 0.77 − 0.93 for PFS; 6 studies, 3478 patients; median OS benefit in months: 2.4 to 4.2). In meta-analysis, risk of any treatment-related adverse events of any grade was lower for ICI than docetaxel as second-line therapy (RR 0.76, 95% CI: 0.73-0.79; 6 studies, 3763 patients).
In first-line therapy of patients with advanced NSCLC, ICI is effective when combined with chemotherapy not depending on PD-L1 expression, or as monotherapy in high PD-L1 expressing tumors. For second-line therapy, single-agent ICI improves efficacy and safety compared to docetaxel.
Monoclonal antibodies (mAb), such as trastuzumab are a valuable addition to breast cancer therapy. Data obtained from neoadjuvant settings revealed that antibody-dependent cell-mediated cytotoxicity ...(ADCC) is a major mechanism of action for the mAb trastuzumab. Conflicting results still call into question whether disease progression, prolonged treatment or concomitant chemotherapy influences ADCC and related immunological phenomena.
We analyzed the activity of ADCC and antibody-dependent cell-mediated phagocytosis (ADCP) of peripheral blood mononuclear cells (PBMCs) from human epidermal growth factor receptor 2 (HER2/neu) positive breast cancer patients receiving trastuzumab therapy either in an adjuvant (n = 13) or metastatic (n = 15) setting as well as from trastuzumab treatment-naive (t-naive) HER2/neu negative patients (n = 15). PBMCs from healthy volunteers (n = 24) were used as controls. ADCC and ADCP activity was correlated with the expression of antibody binding Fc-gamma receptor (FcγR)I (CD64), FcγRII (CD32) and FcγRIII (CD16) on CD14+ (monocytes) and CD56+ (NK) cells, as well as the expression of CD107a+ (LAMP-1) on CD56+ cells and the total amount of CD4+CD25+FOXP3+ (Treg) cells. In metastatic patients, markers were correlated with progression-free survival (PFS).
ADCC activity was significantly down regulated in metastatic, adjuvant and t-naive patient cohorts as compared to healthy controls. Reduced ADCC activity was inversely correlated with the expression of CD107a on CD56+ cells in adjuvant patients. ADCC and ADCP activity of the patient cohorts were similar, regardless of treatment duration or additional chemotherapy. PFS in metastatic patients inversely correlated with the number of peripheral Treg cells.
The reduction of ADCC in patients as compared to healthy controls calls for adjuvant strategies, such as immune-enhancing agents, to improve the activity of trastuzumab. However, efficacy of trastuzumab-specific ADCC and ADCP appears not to be affected by treatment duration, disease progression or concomitant chemotherapy. This finding supports the application of trastuzumab at any stage of the disease.
Metastatic biliary tract cancer (BTC) is a rare and aggressive entity associated with poor prognosis. It represents a major challenge for adequate treatment strategies. In recent years, BTC has ...become a model for precision medicine in gastrointestinal oncology. Therefore, the analysis of the individual molecular profile in BTC patients may lead to targeted therapies for the benefit of patients.
In this Austrian, tricentric, real-world, retrospective analysis, we investigated patients diagnosed with metastatic BTC who underwent molecular profiling between 2013 and 2022.
In total, 92 patients were identified in this tricentric analysis and 205 molecular aberrations, including 198 mutations affecting 89 different genes in 61 patients were found. The predominant mutations were in
(n=17; 22.4%),
(n=17; 22.4%),
(n=7; 9.2%),
(n=7; 9.2%),
(n=7; 9.2%),
(n=7; 9.2%),
(n=6; 7.9%),
(n=6; 7.9%),
(n=4; 5.3%),
(n=4; 5.3%), and
(n=4; 5.3%). Three patients had
amplification. MSI-H status and
fusion genes were each observed in two different patients. One patient had a
mutation. Eventually, 10 patients received targeted therapy, of whom one-half derived clinical benefit.
Molecular profiling of BTC patients is implementable in routine clinical practice and should be regularly employed to detect and exploit molecular vulnerabilities.
Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma and prognostic information is essential in finding the right treatment. This study evaluated the prognostic significance ...of Ki-67 in patients with DLBCL.
Patients with DLBCL, treated with first-line R-CHOP, were retrospectively analyzed in groups of high (>70%) and low (≤70%) Ki-67. Parameters of interest were the international prognostic index (IPI), treatment response, progression-free survival (PFS) and overall survival (OS). A chi-squared test or Fisher's exact test was conducted to analyze categorical variables. Kaplan-Meier and log-rank tests were applied for survival analyses. Finally, a multivariate linear regression analysis was performed, including gender, Ki-67 ≤ 70% or >70%, IPI and presence of B symptoms.
Overall, 58 patients were included. No significant association was found between Ki-67 status and IPI (
= 0.148) or treatment response (
= 0.373). Survival in patients with high Ki-67 was significantly inferior with respect to OS (
= 0.047) but not PFS (
= 0.138). Multivariate linear regression, however, yielded only IPI as a risk factor for OS.
Future studies with larger patient cohorts are needed in order to elucidate the prognostic role of Ki-67 in patients with DLBCL treated with R-CHOP.
Patients with B-cell malignancies are at a higher risk of severe SARS-CoV-2 infections. Nevertheless, extensive data on the immune responses of hematological patients and the efficacy of the third ...dose of the vaccine are scarce. The goal of this study was to determine standardized anti-SARS-CoV-2 S antibody levels and to evaluate differences between treatment modalities in response to the second and third vaccines among patients with B-cell malignancies treated at the University Hospital Krems and the University Hospital of Vienna. The antibody levels of a total of 80 patients were retrospectively analyzed. The results indicate a significant increase in antibody production in response to the third vaccination. The highest increases could be observed in patients in a "watchful-waiting" and "off-therapy" setting. Encouragingly, approximately one-third of patients who did not develop antibodies in response to two vaccinations achieved seroconversion after the third vaccination. "Watchful-waiting", "off-therapy" and treatment with BTK inhibitors were indicative for increased antibody response after the third dose compared to anti-CD19 CAR T-cell and anti-CD-20 antibody treatment. In summary, the results of this study underline the pre-eminent role of the need for complete vaccination with three doses for the development of protective immunity in patients with B-cell malignancies.
•64 of 69 patients’ samples could be profiled. Median alterations: 4 (0 - 23), most frequently TP53, KRAS & CDKN2A/B.•In 13 patients (20% of 64 successful profiles), personalized therapies could be ...initiated.•Effectiveness was seen in 8/13 patients (61,5%) of the precision oncology cohort vs 3/22 (13,5%) treated with chemotherapy.•Kaplan-Meier curves show significant PFS benefit for personalized treated patients (p = 0,0165; median 151 days vs 83 days).•Personalized cancer therapy is effective and feasible also in the setting of a middle-sized oncologic center.
To successfully apply personalized cancer therapies, thorough understanding of the patient's tumor is needed. In-depth, comprehensive genomic profiling systems allow gathering this knowledge by testing hundreds of cancer-related genes. Several large institutions have established precision oncology programs in recent years with promising results for patients. However, especially middle-sized oncologic institutions face challenges to implement such programs.
This study aims to retrospectively analyze the effects of comprehensive genomic tumor profiling with respect to feasibility and effectiveness in a middle-sized oncologic center in Austria.
From May 1st, 2016 to December 31st, 2019 patients at the University Clinic Krems, who suffered from CUP-syndromes plus patients, who were resistant to conventional therapy or have progressed after all available therapy lines, were offered to get their tumors analyzed by comprehensive genomic profiling in order to establish a customized therapy.
Of 69 considered patients, 64 patients’ samples could be profiled. The median number of detected alterations was 4 (minimum 0; maximum 23). Most frequent alterations were reported for TP53, KRAS and CDKN2A/B.
In 13 patients (20% of 64 successful profiles), personalized therapies could be initiated. 22 patients were treated with another line of chemotherapy as no actionable alteration could be detected. Effectiveness, determined by a PFS of the newly initiated therapy longer than 130% of the last conventional therapy line, could be seen in 8 of 13 patients (61,5%) of the precision oncology cohort compared to only 3 of 22 patients (13,5%) in the chemotherapy group. Additionally, Kaplan-Meier curves of PFS demonstrate a significant benefit for personalized treated patients (p = 0,0165 with a median PFS of 151 days, compared to 83 days in the chemotherapy group).
In summary, personalized cancer therapy based on comprehensive genomic profiling is effective and feasible also in the setting of a middle-sized oncologic center.
The mechanisms of allergic sensitization to milk are still elusive. The major allergen Bos d 5 belongs to the lipocalin-family and thus is able to transport numerous ligands. In this study we ...investigated its ability to bind to iron-siderophore complexes and tested the immune-modulatory properties of Bos d 5 in either forms. Structural and in silico docking analysis of Bos d 5 revealed that Bos d 5 is able to bind to iron via catechol-based flavonoids (quercetin, myricetin, luteolin) that act as siderophores as confirmed by spectral-analysis and iron staining. Calculated dissociation constants of docking analyses were below 1 µM by virtual addition of iron. When incubated with human peripheral blood mononuclear cells (PBMCs), only the apo-form of Bos d 5 led to an increase of CD4+positive cells and significantly elevated IL13 and IFNγ-levels. In contrast, holo-Bos d 5 decreased numbers of CD4 expressing cells and induced apoptosis. Taken together, our data give evidence that Bos d 5 is capable of binding iron via siderophores. Moreover, our data support for the first time the notion that the form of application (apo- or holo-form) is decisive for the subsequent immune response. The apo-form promotes Th2 cells and inflammation, whereas the holo-form appears to be immunosuppressive.
It is hypothesized that allergens are at the borderline of self and non-self and, through as yet elusive circumstances, mount a Th2 response for allergic sensitization. The major birch pollen ...allergen Bet v 1 is considered the prototype for the PR-10 protein family causing respiratory allergy. Here, we give structural evidence that Bet v 1 is a lipocalin-like protein with a striking structural resemblance to human lipocalin 2. Lipocalin 2 is highly expressed in the lung where it exerts immunoregulatory functions dependent on being loaded with siderophore-bound iron (holo-form) or not (apo-form). We demonstrate that similar to lipocalin 2, Bet v 1 is capable of binding iron via catechol-based siderophores. Thereby, calculated Kd values of 66 nm surpassed affinities to known ligands nearly by a power of 10. Moreover, we give functional evidence of the immunomodulatory capacity of Bet v 1 being dependent on its iron-loaded state. When incubated to human immune cells, only the apo-form of Bet v 1, but not the holo-form, was able to promote Th2 cells secreting IL13. These results provide for the first time a functional understanding on the allergenicity of Bet v 1 and a basis for future allergen immunotherapies counteracting Th2 immune responses on a molecular basis.
Background: The reason of allergic sensitization to proteins like Bet v 1 is unknown.
Results: Bet v 1 binds iron via catechol-based siderophores. It can modulate human immune cells toward Th2 when not carrying iron.
Conclusion: Bet v 1 modulates immune cells toward Th2 when being devoid of iron.
Significance: We provide the functional basis under which circumstances Bet v 1 becomes an allergen.
Besides its anti-inflammatory effects, cinnamaldehyde has been reported to have anti-carcinogenic activity. Here, we investigated its impact on immune cells.
Activation of nuclear factor-κB by ...cinnamaldehyde (0-10 µg/ml) alone or in combination with lipopolysaccharide was assessed in THP1XBlue human monocytic cell line and in human peripheral blood mononuclear cells (PBMCs). Proliferation and secretion of cytokines (IL10 and TNFα) was determined in primary immune cells and the human cell lines (THP1, Jurkat E6-1 and Raji cell lines) stimulated with cinnamaldehyde alone or in conjunction with lipopolysaccharide. Nitric oxide was determined in mouse RAW264.7 cells. Moreover, different treated PBMCs were stained for CD3, CD20 and AnnexinV.
Low concentrations (up to 1 µg/ml) of cinnamaldehyde resulted in a slight increase in nuclar factor-kB activation, whereas higher concentrations led to a dose-dependent decrease of nuclear factor-kB activation (up to 50%) in lipopolysachharide-stimulated THP1 cells and PBMCs. Accordingly, nitric oxide, interleukin 10 secretion as well as cell proliferation were reduced in lipopolysachharide-stimulated RAW264.7 cells, PBMCs and THP1, Raji and Jurkat-E6 immune cells in the presence of cinnamaldehyde in a concentration-dependent manner. Flow cytometric analysis of PBMCs revealed that CD3+ were more affected than CD20+ cells to apopotosis by cinnamaldehyde.
We attribute the anti-inflammatory properties of cinnamaldehyde to its ability to block nuclear factor-κB activation in immune cells. Treatment with cinnamaldehyde led to inhibition of cell viability, proliferation and induced apoptosis in a dose-dependent manner in primary and immortalized immune cells. Therefore, despite its described anti-carcinogenic property, treatment with cinnamaldehyde in cancer patients might be contraindicated due to its ability to inhibit immune cell activation.
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