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Lymph node metastasis and positive resection margins have been reported to be major determinants of overall survival (OS) and poor recurrence-free survival (RFS) for patients who underwent resection for perihilar cholangiocarcinoma (pCCA). However, the prognostic value of positive lymph nodes independently from resection margin status on OS has not been evaluated.

From the European Cholangiocarcinoma (ENSCCA) registry, patients who underwent resection for pCCA between 1994 and 2021 were included in this retrospective cohort study. The primary outcome was OS stratified for resection margin and lymph node status. The secondary outcome was recurrence-free survival.

A total of 325 patients from 11 different centers and six European countries were included. Of these, 194 (59.7%) patients had negative resection margins. In 113 (34.8%) patients, positive lymph nodes were found. Lymph node status, histological grade, and ECOG performance status were independent prognostic factors for survival. The median OS for N0R0, N0R1, N+R0, and N+R1 was 38, 30, 18, and 12 months, respectively (

< 0.001).

These data indicate that in the presence of positive regional lymph nodes, resection margin status does not determine OS or RFS in patients with pCCA. Achieving negative margins in patients with positive nodes should not come at the expense of more extensive surgery and associated higher mortality.

These data indicate that in the presence of positive regional lymph nodes, resection margin status does not determine OS or RFS in patients with pCCA. Achieving negative margins in patients with positive nodes should not come at the expense of more extensive surgery and associated higher mortality.Prostate cancer (PCa) is the most common cancer in men. Prostate-specific antigen screening is recommended for the detection of PCa. However, its specificity is limited. Thus, there is a need to find more reliable biomarkers that allow non-invasive screening for early-stage PCa. This study aims to explore urine microRNAs (miRs) as diagnostic biomarkers for PCa. We assessed cell-free miR (cfmiR) profiles of urine and plasma samples from pre- and post-operative PCa patients (n = 11) and normal healthy donors (16 urine and 24 plasma) using HTG EdgeSeq miRNA Whole Transcriptome Assay based on next-generation sequencing. SAHA manufacturer Furthermore, tumor-related miRs were detected in formalin-fixed paraffin-embedded tumor tissues obtained from patients with localized PCa. Specific cfmiRs signatures were found in urine samples of localized PCa patients using differential expression analysis. Forty-two cfmiRs that were detected were common to urine, plasma, and tumor samples. These urine cfmiRs may have potential utility in diagnosing early-stage PCa and complementing or improving currently available PCa screening assays. Future studies may validate the findings.Serum- and glucocorticoid-regulated kinases (SGKs) are members of the AGC family of serine/threonine kinases, consisting of three isoforms SGK1, SGK2, and SGK3. SGK1 was initially cloned as a gene transcriptionally stimulated by serum and glucocorticoids in rat mammary tumor cells. It is upregulated in some cancers and downregulated in others. SGK1 increases tumor cell survival, adhesiveness, invasiveness, motility, and epithelial to mesenchymal transition. It stimulates tumor growth by mechanisms such as activation of K+ channels and Ca2+ channels, Na+/H+ exchanger, amino acid and glucose transporters, downregulation of Foxo3a and p53, and upregulation of β-catenin and NFκB. This chapter focuses on major aspects of SGK1 involvement in cancer, its use as biomarker as well as potential therapeutic target.Rehabilitation during chemoradiotherapy (CHRT) might (partly) prevent reduction in physical fitness and nutritional status and could improve treatment tolerance in patients with stage III non-small cell lung cancer (NSCLC). The aim of this proof-of-concept study was to investigate the feasibility of a multimodal program for rehabilitation during CHRT. A home-based multimodal rehabilitation program (partly supervised moderate-intensity physical exercise training and nutritional support) during CHRT was developed in collaboration with patients with stage III NSCLC and specialized healthcare professionals. A predetermined number of six patients with stage III NSCLC (aged > 50 years) who underwent CHRT and participated in this program were monitored in detail to assess its feasibility for further development and optimization of the program. The patient's level of physical functioning (e.g., cardiopulmonary exercise test, six-minute walking test, handgrip strength, body mass index, fat free mass index, energy a prevent physical decline during CHRT.Northeastern Thailand registers the highest worldwide incidence of cholangiocarcinoma (CCA). Most of the cases are associated with liver flukes, while unknown causes comprise approximately 10-30% of cases, and these could be due to occupational exposures. Our aim was to determine the magnitude of occupational causes of CCA in a tertiary hospital in northeastern Thailand. We conducted a cross-sectional study with a sample of 220 patients between March and November 2021. Descriptive statistics were used to analyze the findings. Clinical information and telephone interviews were used to explore significant occupational histories. An occupational consensus meeting was held with two occupational physicians, an industrial hygienist, and a hepatobiliary surgeon to decide on the final diagnosis. The response rate was 90.9% (200/220). Based on the medical records and telephone interviews, researchers found that 11 participants had significant exposure. After occupational consensus, it was agreed that the eleven had possible occupational causes, 5.5% (11/200)-54.5% (6/11) being due to asbestos fibers, 45.5% (5/11) due to dichloromethane, and 9.1% (1/11) due to 1,2-dichloropropane. Only 4% (8/200) had occupational histories collected by their treating physicians. Taken together, occupationally related CCA appears to have been underestimated, so improving occupational history taking is needed to properly identify and classify work-related CCA-both for patient treatment and occupational hazard prevention.Epigenetic abnormalities are extremely widespread in cancer. Some of them are mere consequences of transformation, but some actively contribute to cancer initiation and progression; they provide powerful new biological markers, as well as new targets for therapies. In this review, we examine the recent literature and focus on one particular aspect of epigenome deregulation large-scale chromatin changes, causing global changes of DNA methylation or histone modifications. After a brief overview of the one-dimension (1D) and three-dimension (3D) epigenome in healthy cells and of its homeostasis mechanisms, we use selected examples to describe how many different events (mutations, changes in metabolism, and infections) can cause profound changes to the epigenome and fuel cancer. We then present the consequences for therapies and briefly discuss the role of single-cell approaches for the future progress of the field.

BRAF-mutated colorectal cancers (BRAF-MT CRCs) are known to have poor prognoses. BRAF-MT CRC was reported to be possibly related to the immune-activated phenotype.

This study aimed to investigate the association between the immune microenvironment and prognosis of BRAF-MT CRC.

We evaluated clinical outcomes and investigated the immune profile of the BRAF-MT CRC tumors using the multiplex immunohistochemistry of immune-related markers cytokeratin, programmed death ligand-1 (PD-L1), programmed cell death protein-1 (PD-1), and a cluster of differentiation 8 (CD8).

Out of 2313 tumors, 123 were BRAF-MT tumors. Among them, 86 tumors with available tissue were included. Out of 86 patients, 75 patients were non-good responders (GR), whereas 11 patients were GR. Median progression-free survival after first-line chemotherapy (4.6 vs. 12.4 months,

= 0.008) and overall survival (11.8 vs. 45.0 months) were longer in the GR group (

< 0.001). Median CD8+ T cell (254.29 vs. 656.0,

= 0.092), PD-L1+ tumor cell (0.95 vs.15.56,

= 0.050), PD-L1+ stromal cell (3.17 vs. 72.38,

= 0.025), PD-L1+ tumor and stromal cell (5.08 vs. 74.92,

= 0.032), and PD-1+ stromal cell (45.08 vs. 325.40,

= 0.046) counts were greater in the GR group.

The clinical outcomes of unselected patients with BRAF-MT CRC were generally similar to those in previous studies. Based on the immune profile analysis, higher PD-L1 expression and CD8-positive cell infiltration were observed in BRAF-MT tumors with a good prognosis.

The clinical outcomes of unselected patients with BRAF-MT CRC were generally similar to those in previous studies. Based on the immune profile analysis, higher PD-L1 expression and CD8-positive cell infiltration were observed in BRAF-MT tumors with a good prognosis.Cancer contains tumor-initiating stem-like cells (TICs) that are resistant to therapies. Hepatocellular carcinoma (HCC) incidence has increased twice over the past few decades, while the incidence of other cancer types has trended downward globally. Therefore, an understanding of HCC development and therapy resistance mechanisms is needed for this incurable malignancy. This review article describes links between immunotherapies and microbiota in tumor-initiating stem-like cells (TICs), which have stem cell characteristics with self-renewal ability and express pluripotency transcription factors such as NANOG, SOX2, and OCT4. This review discusses (1) how immunotherapies fail and (2) how gut dysbiosis inhibits immunotherapy efficacy. Gut dysbiosis promotes resistance to immunotherapies by breaking gut immune tolerance and activating suppressor immune cells. Unfortunately, this leads to incurable recurrence/metastasis development. Personalized medicine approaches targeting these mechanisms of TIC/metastasis-initiating cells are emerging targets for HCC immunotherapy and microbiota modulation therapy.ET resistance is a critical problem for estrogen receptor-positive (ER+) breast cancer. In this study, we have investigated how alterations in sphingolipids promote cell survival in ET-resistant breast cancer. We have performed LC-MS-based targeted sphingolipidomics of tamoxifen-sensitive and -resistant MCF-7 breast cancer cell lines. Follow-up studies included treatments of cell lines and patient-derived xenograft organoids (PDxO) with small molecule inhibitors; cytometric analyses to measure cell death, proliferation, and apoptosis; siRNA-mediated knockdown; RT-qPCR and Western blot for gene and protein expression; targeted lipid analysis; and lipid addback experiments. We found that tamoxifen-resistant cells have lower levels of ceramides and hexosylceramides compared to their tamoxifen-sensitive counterpart. Upon perturbing the sphingolipid pathway with small molecule inhibitors of key enzymes, we identified that CERK is essential for tamoxifen-resistant breast cancer cell survival, as well as a fulvestrant-resistant PDxO. CERK inhibition induces ceramide-mediated cell death in tamoxifen-resistant cells. Ceramide-1-phosphate (C1P) partially reverses CERK inhibition-induced cell death in tamoxifen-resistant cells, likely through lowering endogenous ceramide levels. Our findings suggest that ET-resistant breast cancer cells maintain lower ceramide levels as an essential pro-survival mechanism. Consequently, ET-resistant breast cancer models have a unique dependence on CERK as its activity can inhibit de novo ceramide production.