Cancer Biology & Medicine最新文献

Objective: Malignant peritoneal mesothelioma (MPM) is a rare primary malignant tumor with an extremely poor prognosis that currently lacks effective treatment options. This study investigated the in vitro and in vivo efficacy of natural killer (NK) cells for treatment of MPM.

Methods: An in vitro study was conducted to assess the cytotoxicity of NK cells from umbilical cord blood to MPM cells with the use of a high-content imaging analysis system, the Cell Counting Kit-8 assay, and Wright-Giemsa staining. The level of NK cell effector molecule expression was detected by flow cytometry and enzyme-linked immunosorbent assays. The ability of NK cells to kill MPM cells was determined based on live cell imaging, transmission electron microscopy, and scanning electron microscopy. An in vivo study was conducted to assess the efficacy and safety of NK cell therapy based on the experimental peritoneal cancer index, small animal magnetic resonance imaging, and conventional histopathologic, cytologic, and hematologic studies.

Results: NK cells effectively killed MPM cells through the release of effector molecules (granzyme B, perforin, interferon-γ, and tumor necrosis factor-α) in a dose- and density-dependent manner. The NK cell killing process potentially involved four dynamic steps: chemotaxis; hitting; adhesion; and penetration. NK cells significantly reduced the tumor burden, diminished ascites production, and extended survival with no significant hematologic toxicity or organ damage in NOG mice.

Conclusions: NK cell immunotherapy inhibited proliferation of MPM cells in vitro and in vivo with a good safety profile.

Ubiquitination, a multifaceted post-translational modification, regulates protein function, degradation, and gene expression. The pivotal role of ubiquitination in the pathogenesis and progression of cancer, including colorectal, breast, and liver cancer, is well-established. Osteosarcoma, an aggressive bone tumor predominantly affecting adolescents, also exhibits dysregulation of the ubiquitination system, encompassing both ubiquitination and deubiquitination processes. This dysregulation is now recognized as a key driver of osteosarcoma development, progression, and chemoresistance. This review highlights recent progress in elucidating how ubiquitination modulates tumor behavior across signaling pathways. We then focus on the mechanisms by which ubiquitination influences osteosarcoma cell function. Finally, we discuss the potential for targeting the ubiquitin-proteasome system in osteosarcoma therapy. By unraveling the impact of ubiquitination on osteosarcoma cell physiology, we aim to facilitate the development of novel strategies for prognosis, staging, treatment, and overcoming chemoresistance.

Gender disparities are evident across different types of digestive system cancers, which are typically characterized by a lower incidence and mortality rate in females compared to males. This finding suggests a potential protective role of female steroid hormones, particularly estrogen, in the development of these cancers. Estrogen is a well-known sex hormone that not only regulates the reproductive system but also exerts diverse effects on non-reproductive organs mediated through interactions with estrogen receptors (ERs), including the classic (ERα and ERβ) and non-traditional ERs [G protein-coupled estrogen receptor (GPER)]. Recent advances have contributed to our comprehension of the mechanisms underlying ERs in digestive system cancers. In this comprehensive review we summarize the current understanding of the intricate roles played by estrogen and ERs in the major types of digestive system cancers, including hepatocellular, pancreatic, esophageal, gastric, and colorectal carcinoma. Furthermore, we discuss the potential molecular mechanisms underlying ERα, ERβ, and GPER effects, and propose perspectives on innovative therapies and preventive measures targeting the pathways regulated by estrogen and ERs. The roles of estrogen and ERs in digestive system cancers are complicated and depend on the cell type and tissue involved. Additionally, deciphering the intricate roles of estrogen, ERs, and the associated signaling pathways may guide the discovery of novel and tailored therapeutic and preventive strategies for digestive system cancers, eventually improving the care and clinical outcomes for the substantial number of individuals worldwide affected by these malignancies.

Objective: The presence of complex components in Chinese herbal medicine (CHM) hinders identification of the primary active substances and understanding of pharmacological principles. This study was aimed at developing a big-data-based, knowledge-driven in silico algorithm for predicting central components in complex CHM formulas.

Methods: Network pharmacology (TCMSP) and clinical (GEO) databases were searched to retrieve gene targets corresponding to the formula ingredients, herbal components, and specific disease being treated. Intersections were determined to obtain disease-specific core targets, which underwent further GO and KEGG enrichment analyses to generate non-redundant biological processes and molecular targets for the formula and each component. The ratios of the numbers of biological and molecular events associated with a component were calculated with a formula, and entropy weighting was performed to obtain a fitting score to facilitate ranking and improve identification of the key components. The established method was tested on the traditional CHM formula Danggui Sini Decoction (DSD) for gastric cancer. Finally, the effects of the predicted critical component were experimentally validated in gastric cancer cells.

Results: An algorithm called Chinese Herb Medicine-Formula vs. Ingredients Efficacy Fitting & Prediction (CHM-FIEFP) was developed. Ferulic acid was identified as having the highest fitting score among all tested DSD components. The pharmacological effects of ferulic acid alone were similar to those of DSD.

Conclusions: CHM-FIEFP is a promising in silico method for identifying pharmacological components of CHM formulas with activity against specific diseases. This approach may also be practical for solving other similarly complex problems. The algorithm is available at http://chm-fiefp.net/.

Neutrophils, which originate from the bone marrow and are characterized by a segmented nucleus and a brief lifespan, have a crucial role in the body's defense against infections and acute inflammation. Recent research has uncovered the complex roles of neutrophils as regulators in tumorigenesis, during which neutrophils exhibit a dualistic nature that promotes or inhibits tumor progression. This adaptability is pivotal within the tumor microenvironment (TME). In this review, we provide a comprehensive characterization of neutrophil plasticity and heterogeneity, aiming to illuminate current research findings and discuss potential therapeutic avenues. By delineating the intricate interplay of neutrophils in the TME, this review further underscores the urgent need to understand the dual functions of neutrophils with particular emphasis on the anti-tumor effects to facilitate the development of effective therapeutic strategies against cancer.