RSK4 promotes the metastasis of clear cell renal cell carcinoma by activating RUNX1-mediated angiogenesis.

Ribosomal S6 protein kinase 4 (RSK4), a member of the serine‒threonine kinase family, plays a vital role in the Ras‒MAPK pathway. This kinase is responsible for managing several cellular activities, including cell growth, proliferation, survival, and mobility. In this study, we observed higher RSK4 protein expression in clear cell renal cell carcinoma (ccRCC) than in normal kidney tissue, and the overexpression of RSK4 might predict poor outcomes for ccRCC patients.

Immune senescence: A key player in cancer biology.

With the rapid development of immunological techniques in recent years, our understanding of immune senescence has gradually deepened, but the role of immune senescence in cancer biology remains incompletely elucidated. Understanding these mechanisms and interactions is crucial for the development of tumor biology. This review examines five key areas: the classification and main features of immune senescence, factors influencing immune cell senescence in cancer, the reciprocal causal cycle between immune senescence and malignancy, and the potential of immune senescence as a target for cancer immunotherapy.

Clear-cell papillary renal cell tumour: New insights into clinicopathological features and molecular landscape after renaming by 5th WHO classification.

Objective: Clear cell papillary renal cell tumour (CCPRCT) is a kind of renal epithelial cell tumor, and was renamed by the 5th WHO due to its specific epidemiology and clinicopathological characteristics. However, the biological mechanism and molecular basis of CCPRCT still need to be further clarified. This study aims to comprehensively evaluate clinicopathologic and molecular characteristics of CCPRCC, and particularly compare it with other more prevalent subtypes of renal cell carcinoma.

The mitochondrial genome-encoded peptide MOTS-c interacts with Bcl-2 to alleviate nonalcoholic steatohepatitis progression.

Nonalcoholic steatohepatitis (NASH) is a metabolism-associated fatty liver disease with accumulated mitochondrial stress, and targeting mitochondrial function is a potential therapy. The mitochondrial genome-encoded bioactive peptide MOTS-c plays broad physiological roles, but its effectiveness and direct targets in NASH treatment are still unclear. Here, we show that long-term preventive and short-term therapeutic effects of MOTS-c treatments alleviate NASH-diet-induced liver steatosis, cellular apoptosis, inflammation, and fibrosis.

Low expression of H3K27me3 is associated with poor prognosis in conventional chordoma.

Purpose: Chordoma is a rare and locally invasive neoplasm, and the prognostic factors are limited. Deregulation of Histone 3 lysine 27 (H3K27) trimethylation (H3K27me3) is considered to be related with poor prognosis in some tumors. The purpose of this study was to detect the expression of H3K27me3 in chordomas and analyze the correlation with clinicopathological features and explore the roles as potential prognostic markers and therapeutic targets.

-rearranged fibroblastic tumor: A case with twice recurrence and literature review.

-rearranged fibroblastic tumor is a recently described entity that mostly occurs in acral locations. Only 15 cases have been reported in the English literature, with a wide age range and marked female predominance. The most common sites are the foot, followed by the hand and the distal lower leg.

Phosphorylation of PBK/TOPK Tyr74 by JAK2 promotes Burkitt lymphoma tumor growth.

Burkitt lymphoma (BL), which is characterized by high invasiveness, is a subgroup of non-Hodgkin lymphoma. Although BL is regarded as a highly curable disease, especially for children, some patients unfortunately still do not respond adequately. The understanding of the etiology and molecular mechanisms of BL is still limited, and targeted therapies are still lacking.

High RSK4 expression constitutes a predictor of poor prognosis for patients with clear cell renal carcinoma.

Background: This research focuses on exploring RSK4 protein expression within Clear Cell Renal Cell Carcinoma (ccRCC), based on these investigations on level of expressions coupled with the relevance to clinicopathologic features and clinical outcomes.

Methods: The expression of RSK4 in 48 ccRCC and 20 hydronephrosis samples were under the detection of immunohistochemistry; besides, its relevance to the combination of clinicopathologic features with prognosis was committed in virtue of statistical approaches.

Results: The 48 ccRCC samples included 36 (75%, 36/48) positive for RSK4, while the positive rate in hydronephrosis samples were 5 (25%, 5/20).

TOPK: A new predictor of the therapeutic response to neoadjuvant chemotherapy and prognosis in triple-negative breast cancer.

Background: Triple-negative breast cancer (TNBC) has a high probability of relapse and poor overall survival. Neoadjuvant chemotherapy (NACT) is currently a routine treatment strategy for TNBC, but some patients do not respond well. T-LAK cell-originated protein kinase (TOPK) is highly expressed in breast cancer cells and contributes to cancer cell proliferation.

Discovery, Optimization, and Structure-Activity Relationship Study of Novel and Potent RSK4 Inhibitors as Promising Agents for the Treatment of Esophageal Squamous Cell Carcinoma.

Ribosomal S6 protein kinase 4 (RSK4) was identified to be a promising target for the treatment of esophageal squamous cell carcinoma (ESCC) in our previous research, whose current treatments are primarily chemotherapy and radiotherapy due to the lack of targeted therapy. However, few potent and specific RSK4 inhibitors are reported. In this study, a series of 1,4-dihydro--pyrimido[4,5-][1,3]oxazin-2-ones derivatives were designed and synthesized as novel and potent RSK4 inhibitors.

Some pleomorphic adenomas of the breast share PLAG1 rearrangements with the analogous tumour of the salivary glands.

Aims: Pleomorphic adenoma (PA) of the breast, and especially its malignant transformation, is extremely rare and represents a diagnostic pitfall. Molecular alterations in this entity have not been investigated. We aimed to examine the clinicopathological features of our breast PAs and perform molecular analysis.

Tumor Immune Microenvironment Components and Checkpoint Molecules in Anaplastic Variant of Diffuse Large B-Cell Lymphoma.

Background: Anaplastic diffuse large B-cell lymphoma(A-DLBCL) is a rare morphological subtype characterized by the presence of polygonal, bizarre-shaped tumor cells. Our previous research found that A-DLBCL displays many genetic alterations and biological features that differ greatly from those of ordinary DLBCL. However, the status of tumor immune microenvironment components and checkpoint molecules in A-DLBCL remains unclear.

Genomic Mutation Profile of Primary Gastrointestinal Diffuse Large B-Cell Lymphoma.

Primary gastrointestinal diffuse large B-cell lymphoma (GI-DLBCL) is the most common gastrointestinal lymphoma, but its genetic features are poorly understood. We performed whole-exome sequencing of 25 primary tumor samples from patients with GI-DLBCL and 23 matched normal tissue samples. Oncogenic mutations were screened, and the correlations between genetic mutations and clinicopathological characteristics were analyzed.

Decreased infiltration of CD4 Th1 cells indicates a good response to ursodeoxycholic acid (UDCA) in primary biliary cholangitis.

Background: Primary biliary cholangitis (PBC) is characterized by nonsuppurative destructive cholangitis and is thought to be an autoimmune disorder. Currently, ursodeoxycholic acid (UDCA) is the only FDA approved first-line therapy for PBC, but up to nearly one-third of patients do not achieve a complete response to this treatment. Adaptive immune cells, including T cells and B cells, have been found in the portal tracts and the bile duct epithelium and play a role in the pathogenesis of PBC, but the importance of these cells for evaluating the therapeutic response to UDCA in PBC has not yet been studied.

Prognostic value of tumoral and peritumoral magnetic resonance parameters in osteosarcoma patients for monitoring chemotherapy response.

Objectives: To evaluate parameters of diffusion-weighted imaging (DWI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) as early imaging indicators of tumor histologic response to pre-operative neoadjuvant chemotherapy and as probable prognostic factors for event-free survival (EFS) and overall survival in osteosarcoma (OS) in both tumoral and peritumoral areas.

Methods: Thirty-four OS patients who received three courses of neoadjuvant chemotherapy followed by surgery during 2014-2018 were enrolled in this study. All patients underwent baseline and post-chemotherapy DWI and DCE-MRI.

The clinicopathological and molecular features of sinusoidal large B-cell lymphoma.

We report 17 cases of sinusoidal large B-cell lymphoma (SLBCL). Clinical, morphologic, immunophenotypic, and molecular features were detected and analyzed. All cases showed an obvious sinusoidal growth pattern, usually associated with residual atrophic lymphoid tissue.

Ribosomal S6 protein kinase 4 promotes radioresistance in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive cancers and is highly resistant to current treatments. ESCC harbors a subpopulation of cells exhibiting cancer stem-like cell (CSC) properties that contribute to therapeutic resistance including radioresistance, but the molecular mechanisms in ESCC CSCs are currently unknown. Here, we report that ribosomal S6 protein kinase 4 (RSK4) plays a pivotal role in promoting CSC properties and radioresistance in ESCC.

Expression of RSK4, CD44 and MMP-9 is upregulated and positively correlated in metastatic ccRCC.

Background: To investigate the expression and function of RSK4, MMP-9 and CD44 in primary clear cell renal cell carcinoma (primary ccRCC) and metastatic clear cell renal cell carcinoma (metastatic ccRCC), as well as the correlation with clinicopathological features of patients.

Method: The expression levels of RSK4, CD44 and MMP-9 in 52 primary ccRCC samples and 48 metastatic ccRCC samples were detected by immunohistochemistry, and the relationship between RSK4, CD44 and MMP-9 expression and clinicopathological features as well as prognosis of metastatic ccRCC patients was statistically analysed. Ectopic RSK4 expression in ccRCC cell lines was performed to determine its effect on cell cycle regulation, tumour invasiveness, and metastatic capability.

Progress in triple negative breast carcinoma pathophysiology: Potential therapeutic targets.

Triple-negative breast carcinoma (TNBC) is a subtype of breast carcinoma defined by negativity for estrogen receptor (ER) or progesterone receptor (PR) by immunohistochemical analysis and negativity for human epidermal growth factor receptor (Her2) by immunohistochemistry or in situ hybridization. TNBC is clinically marked by its high aggressiveness, particularly poor outcomes including a low survival rate, and the lack of specific and effective treatments. Therefore, new potential targets for the treatment of TNBC must be identified.

Small-cell carcinoma-associated ovarian mucinous carcinoma: A case report and literature review.

Neuroendocrine neoplasm-associated ovarian mucinous carcinoma occurs extremely rarely. Here, we report an ovarian composite tumor consisting of small-cell carcinoma and mucinous carcinoma in a 51-year-old woman presented with abdominal distention. Ultrasonography revealed the presence of a complex irregular cystic solid mass.

Genetic alterations in cell cycle regulation-associated genes may promote primary progression of gastrointestinal stromal tumors.

Gastrointestinal stromal tumors (GISTs) are one of the most common mesenchymal tumor types and usually contain KIT or PDGFRA mutations. GISTs with concomitant low- and high-grade components are seen in clinical practice. Herein, we retrospectively analyzed the histological characteristics and immunohistochemical results of 22 GIST cases with concomitant low- and high-grade tumors.

Lineage-negative lymphoma with a helper innate lymphoid cell phenotype.

Helper innate lymphoid cells (ILCs) were recently recognized as lineage-negative lymphoid cells that do not express rearranged receptors and have important effector and regulatory functions in innate immunity. However, to our knowledge, no cases of hematological malignancies arising from helper ILCs have ever been reported in the literature. Here, we report a case of a 17-year-old man with multiple lymphadenopathy who was diagnosed with lineage-negative lymphoma that displayed a helper ILC phenotype.