A Biopsy-Controlled Prospective Study of Contrast-Enhancing Diffuse Glioma Infiltration Based on FET-PET and FLAIR.

Accurately defining glioma infiltration is crucial for optimizing radiotherapy and surgery, but glioma infiltration is heterogeneous and MRI imperfectly defines the tumor extent. Currently, it is impossible to determine the tumor infiltration gradient within a FLAIR signal. O-(2-[18F]fluoroethyl)-L-tyrosine (FET)-PET often reveals high-grade glioma infiltration beyond contrast-enhancing areas on MRI. Here, we studied FET uptake dynamics in tumor and normal brain structures by dual-timepoint (10 min and 40-60 min post-injection) acquisition to optimize analysis protocols for defining glioma infiltration. Over 300 serial stereotactic biopsies from 23 patients (mean age 47, 12 female/11 male) of diffuse contrast-enhancing gliomas were taken from areas inside and outside contrast enhancement or outside the FET hotspot but inside FLAIR. The final diagnosis was G4 in 11, grade 3 in 10, and grade 2 in 2 patients. The target-to-background (TBRs) ratios and standardized uptake values (SUVs) were calculated in areas used for biopsy planning and in background structures. The optimal method and threshold values were determined to find a preferred strategy for defining glioma infiltration. Standard thresholding (1.6× uptake in the contralateral brain) in standard acquisition PET images differentiated a tumor of any grade from astrogliosis, although the uptake in astrogliosis and grade 2 glioma was similar. Analyzing an optimal strategy for infiltration volume definition astrogliosis could be accurately differentiated from tumor samples using a choroid plexus as a background. Early acquisition improved the AUC in many cases, especially within FLAIR, from 56% to 90% sensitivity and 41% to 61% specificity (standard TBR 1.6 vs. early TBR plexus). The current FET-PET evaluation protocols for contrast-enhancing gliomas are limited, especially at the tumor border where grade 2 tumor and astrogliosis have similar uptake, but using choroid plexus uptake in early acquisitions as a background, we can precisely define a tumor within FLAIR that was outside of the scope of current FET-PET protocols.

An optimal dose-fractionation for stereotactic body radiotherapy in peripherally, centrally and ultracentrally located early-stage non-small lung cancer.

Stereotactic body radiotherapy (SBRT), also known as stereotactic ablative radiotherapy (SABR), is commonly used in inoperable patients with early-stage non-small lung cancer (NSCLC). This treatment has good outcomes and low toxicity in peripherally located tumors. However, in lesions which are located close to structures such as the bronchial tree or mediastinum the risk of severe toxicity increases. This review summarizes the evidence of dose-fractionation in SBRT of NSCLC patients in various locations.

Expression differences between proteins responsible for DNA damage repair according to the Gleason grade as a new heterogeneity marker in prostate cancer.

Introduction: The purpose of this research was to explore the correlation between Gleason score and pattern and the expression of the MLH1, MSH2, MDC1, TP53BP1 proteins in prostate cancer (PC). Prostate cancer development is related to errors in DNA, among others double-strand breaks (DSB) and changes in the base sequence of the DNA. These errors should be repaired through mismatch (MMR) or DSB repair proteins such as MSH2, MLH1, MDC1 and TP53BP1. Material and methods: A total of 500 prostate cancer specimens were recruited in this study. From among all gathered specimens the 52 most suitable cases were selected. The expression of examined proteins was detected by immunohistochemistry, and its correlation with the Gleason score and pattern were further analyzed through standard statistical algorithms. Results: The results show a significant correlation between Gleason pattern and the nuclear expression of the MSH2 protein and the cytoplasmic expression of the MLH1 protein. Gleason score significantly correlates with the nuclear and the cytoplasmic expression of the MSH2 protein and the cytoplasmic expression of the MDC1 protein. There is no correlation between the nuclear or cytoplasmic expression of the TP53BP1 protein and Gleason pattern or score. Conclusions: Our study suggests that the aberration in the MMR repair mechanism may be significantly more important regarding the grading among PC cells in comparison to the impact of alterations in the DSB repair mechanism. The lack of correlation between expression of the TP53BP1 protein and Gleason pattern and Gleason score suggests that the radiation resistance of PC is independent of alterations connected with TP53BP1.

The clinical, prognostic and therapeutic significance of liver cancer stem cells and their markers.

Hepatocellular carcinoma (HCC) is the fourth most common cause of death among cancers. The poor prognosis of HCC might be caused by a population of cancer stem cells (CSC). CSC have similar characteristics to normal stem cells and are responsible for cancer recurrence, chemoresistance, radioresistance and metastasis. Liver cancer stem cells (LCSC) are identified via specific surface markers, such as CD44, CD90, CD133, and EpCAM (CD326). Recent studies suggested a complex interaction between mentioned LCSC markers and clinical features of HCC. A high expression of CSC is correlated with a negative prognostic factor after surgical resection of HCC and is connected with more aggressive tumor behavior. Moreover, LCSC might be responsible for increasing resistance to sorafenib, a kinase inhibitor drug. A reduction in the LCSC population may be crucial to successful advanced HCC therapy.

The prognostic value of leucine-rich repeat-containing G-protein (Lgr5) and its impact on clinicopathological features of colorectal cancer.

INTRODUCTION: Colorectal cancer (CRC) constitutes one of the most prevalent malignancies in the world. Recent research suggests that cancer stem cells (CSCs) are responsible for tumor cell's malignant behavior in CRC. This study has been designed to determinate clinical implications of CSC markers: CD44, DCLK1, Lgr5, and ANXA2 in CRC. MATERIALS AND METHODS: The study was performed on tissue samples which were collected from 89 patients undergoing colectomy. Formalin-fixed paraffin-embedded tissue blocks with representative tumor areas were identified and corded. Immunohistochemical staining was performed using anti-CD44, anti-LGR5, anti-ANXA2, and anti-DCLK1 antibodies. The H-score system was utilized to determine the immunointensity of CRC cells. RESULTS: The lower expression of Lgr5 was significantly correlated with the presence of lymph-node metastases (p = 0.011), while high expression of Lgr5 was statistically significant in vascular invasion in examined cancer tissue samples (p = 0.027). Moreover, a high H-score value of Lgr5 expression was significantly related to a reduced overall survival rate (p = 0.043). CONCLUSION: Our results suggest a strong relationship between CSC marker Lgr5 and vascular invasion, presence of lymph-node metastasis, and overall poor survival. The presence of Lgr5 might be an unfavorable prognostic factor, and its high level in cancer tissue is related to an aggressive course. This marker could also be used to access the effectiveness of the treatment.

The impact of TP53BP1 and MLH1 on metastatic capability in cases of locally advanced prostate cancer and their usefulness in clinical practice.

BACKGROUND: Lymph node (LN) metastases increase the risk of death from prostate cancer (CaP). The dysfunction of factors responsible for DNA injury detection may promote the evolution of localized primary tumors into the metastatic form. METHODS: In this study, 52 cases of CaP were analyzed. The cases were divided into groups of CaP without metastases (N0), with metastases to the LNs (N+), and metastatic LN tissue. Immunohistochemical examinations were performed with antibodies against MDC1, TP53BP1, MLH1, MSH2, MSH6, and PMS2. RESULTS: Statistical analysis showed lower nuclear expression of TP53BP1 in N+ cases than in N0 cases (P = 0.026). Nuclear TP53BP1 expression was lower in LN cases than in N+ cases (P = 0.019). Statistical analysis showed lower nuclear expression of MLH1 in N+ cases than in to N0 cases (P = 0.003). CONCLUSION: Decreased expression of both MLH1 and TP53B1 were demonstrated in N+ cases of CaP. This observation could help to determine the risk of nodal metastasis, and to select appropriate treatment modalities for patients with locally advanced CaP.

Markers of pancreatic cancer stem cells and their clinical and therapeutic implications.

Pancreatic cancer (PC) is the fourth most common cause of death among all cancers. Poor prognosis of PC may be caused by a prevalence of cancer stem cells (CSCs). CSCs are a population of cancer cells showing stem cell-like characteristics. CSCs have the ability to self-renew and may initiate tumorigenesis. PC CSCs express markers such as CD133, CD24, CD44, DCLK1, CXCR4, ESA, Oct4 and ABCB1. There is a wide complexity of interaction and relationships between CSC markers in PC. These markers are negative prognostic factors and are connected with tumor recurrence and clinical progression. Additionally, PC CSCs are resistant to treatment with gemcitabine. Thus, most current therapies for PC are ineffective. Numerous studies have shown, that targeting of these proteins may increase both disease-free and overall survival in PC.

The Essential Role of DCLK1 in Pathogenesis, Diagnostic Procedures and Prognostic Stratification of Colorectal Cancer.

Colorectal cancer (CRC) is the second most prevalent type of cancer among males and the third among females. CRC recurrence and poor prognosis may be related to the prevalence of chemotherapy-resistant cancer stem cells (CSCs). Recent studies have indicated the role of doublecortin-like kinase 1 (DCLK1) protein as a marker of CSC in CRC. This review focuses on the role of DCLK1 in CRC. Long-lived DCLK1-positive tuft cells can function as cancer-initiating cells. Numerous studies have shown DCLK1 overexpression to be significantly correlated with the stage of disease, the presence of metastasis and poor survival rate. DCLK1 may also be used to identify patients at high risk and those with chemotherapy-resistant tumors. DCLK1-specific drugs are examined as potential cancer treatments.