Immunotherapy combinations with tyrosine-kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) had significantly improved outcomes of patients with mRCC. Predictive and prognostic factors are crucial to improve patients' counseling and management. The present study aimed to externally validate the prognostic value of a previously developed red cell-based score, including hemoglobin (Hb), mean corpuscular volume (MCV) and red cell distribution width (RDW), in patients with mRCC treated with first-line immunotherapy combinations (TKI plus ICI or ICI plus ICI). We performed a sub-analysis of a multicentre retrospective observational study (ARON-1 project) involving patients with mRCC treated with first-line immunotherapy combinations. Uni- and multivariable Cox regression models were used to assess the correlation between the red cell-based score and progression-free survival (PFS), and overall survival (OS). Logistic regression were used to estimate the correlation between the score and the objective response rate (ORR). The prognostic impact of the red cell-based score on PFS and OS was confirmed in the whole population regardless of the immunotherapy combination used [median PFS (mPFS): 17.4 vs 8.2 months, HR 0.66, 95% CI 0.47-0.94; median OS (mOS): 42.0 vs 17.3 months, HR 0.60, 95% CI 0.39-0.92; p < 0.001 for both]. We validated the prognostic significance of the red cell-based score in patients with mRCC treated with first-line immunotherapy combinations. The score is easy to use in daily clinical practice and it might improve patient counselling.
The transcription factor c-Myb is an oncoprotein promoting cell proliferation and survival when aberrantly activated/expressed, thus contributing to malignant transformation. Overexpression of c-Myb has been found in leukemias, breast, colon and adenoid cystic carcinoma. Recent studies revealed its expression also in osteosarcoma cell lines and suggested its functional importance during bone development. However, the relevance of c-Myb in control of osteosarcoma progression remains unknown. A retrospective clinical study was carried out to assess a relationship between c-Myb expression in archival osteosarcoma tissues and prognosis in a cohort of high-grade osteosarcoma patients. In addition, MYB was depleted in metastatic osteosarcoma cell lines SAOS-2 LM5 and 143B and their growth, chemosensitivity, migration and metastatic activity were determined. Immunohistochemical analysis revealed that high c-Myb expression was significantly associated with poor overall survival in the cohort and metastatic progression in young patients. Increased level of c-Myb was detected in metastatic osteosarcoma cell lines and its depletion suppressed their growth, colony-forming capacity, migration and chemoresistance in vitro in a cell line-dependent manner. MYB knock-out resulted in reduced metastatic activity of both SAOS-2 LM5 and 143B cell lines in immunodeficient mice. Transcriptomic analysis revealed the c-Myb-driven functional programs enriched for genes involved in the regulation of cell growth, stress response, cell adhesion and cell differentiation/morphogenesis. Wnt signaling pathway was identified as c-Myb target in osteosarcoma cells. Taken together, we identified c-Myb as a negative prognostic factor in osteosarcoma and showed its involvement in the regulation of osteosarcoma cell growth, chemosensitivity, migration and metastatic activity.
- MeSH
- lidé MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- nádory kostí * patologie MeSH
- osteosarkom * patologie MeSH
- pohyb buněk genetika MeSH
- prognóza MeSH
- proliferace buněk MeSH
- regulace genové exprese u nádorů MeSH
- retrospektivní studie MeSH
- signální dráha Wnt MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Secondary tumors of the ovary account for 10-25% of all ovarian malignancies. The most common tumors that give rise to ovarian metastases include breast, colorectal, endometrial, stomach, and appendix cancer. The correct diagnosis of secondary ovarian tumors may be challenging as they are not infrequently misdiagnosed as primary ovarian cancer, particularly in the case of mucinous adenocarcinomas. The distinction from the latter is essential, as it requires different treatment. Immunohistochemistry plays an important role in distinguishing primary ovarian tumors from extra-ovarian metastases and, furthermore, may suggest the primary tumor site. Despite extensive study, some cases remain equivocal even after assessing a broad spectrum of antigens. Therefore, gene expression profiling represents an approach able to further discriminate equivocal findings, and one that has been proven effective in determining the origin of cancer of unknown primary site. The available data concerning secondary ovarian tumors is rather limited owing to the relative heterogeneity of this group and the practical absence of any prospective trials. However, several intriguing questions are encountered in daily practice, including rational diagnostic workup, the role of cytoreductive surgery, and consequent adjuvant chemotherapy. This review seeks to address these issues comprehensively and summarize current knowledge on the epidemiology, pathogenesis, and management of secondary ovarian tumors, including further discussion on the different pathways of metastatisation, metastatic organotropism, and their possible molecular mechanisms.
- MeSH
- karcinogeneze MeSH
- lidé MeSH
- mucinózní adenokarcinom diagnóza sekundární terapie MeSH
- nádory vaječníků diagnóza sekundární terapie MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Objectives Nuclear factor-kappaB (NF-kappaB), especially p65 subunit, seems to be associated with origin and progression of cancer. The aim of the study was to determine expression of NF-kappaB/p65 in rectal cancer patients before and after radiotherapy as well as to assess the relationship between NF-kappaB/p65 expression, other tumor characteristics, and disease progression. Further aim was to evaluate whether expression of NF-kappaB/p65 in tumor tissue may serve as a predictive marker of patient outcome. Patients and methods Twenty-five patients with rectal cancer undergoing pre-operative radiotherapy were included in the study. Unirradiated rectal cancer specimens were obtained from diagnostic colonoscopy. Irradiated rectal cancer specimens were obtained from surgically removed part of the rectum with the tumor. NF-kappaB/p65 expression was determined by immunohistochemistry. Results Cytoplasmic positivity in cancer cells and nuclear positivity in lymphocytes were detected. In post-radiotherapy specimens single tumor cells or small clones of them deeply infiltrating the wall of the rectum, that were characterized by high NF-kappaB/p65 expression, were found. Patients with presence of these cells in post-radiotherapy specimens have worse clinical outcome in terms of overall survival and disease-free interval. Conclusion While the NF-kappaB/p65 positive staining of the epithelial cells did not have any clinical implications in this study, it may be of clinical significance in the future. Residual invasively growing cancer cells with high NF-kappaB/p65 positivity found in specimens after radiotherapy and surgery may be used to find what patients have a worse outcome. Thus, patients being at risk of cancer progression and requiring more aggressive anti-cancer therapy may be identified.
- MeSH
- dospělí MeSH
- financování organizované MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové biomarkery analýza MeSH
- nádory rekta chemie patologie radioterapie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- transkripční faktor RelA analýza MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
BACKGROUND: The use of bisphosphonates (BPs) represents a standard therapy of bone metastatic disease from breast cancer and has been incorporated in many systemic international guidelines. We have tried to evaluate the use of BPs in current clinical practice across the Czech Republic. PARTICIPANTS AND METHODS: A covering letter, questionnaires and pre-paid envelopes were mailed to the head oncologists of 64 workplaces of Czech Oncology Society. Total 310 questionnaires were sent out. The questionnaire consisted of 23 questions. RESULTS: The questionnaires were completed and returned by 91 oncologists from 32 workplaces. Most of the responding oncologists worked at university hospitals (42%), the most frequent length of work experience was 5 to 10 years (30%) and the most frequent rate of breast cancer patients was from 10 to 25% (45%). Ninety-five percent of the oncologists regularly initiated BP therapy, and oral clodronate was the first choice BP (77%). Once initiated, the treatment was discontinued in less than 5% patients (24%). Seventy-one (79%) oncologists stated that the most important reason leading to therapy termination was impairment of performance status. CONCLUSIONS: The consensual agreement pointed out that it could be a fundamental step towards establishing the national treatment guidelines for the BP use in metastatic breast cancer patients.
