Exosomes in cancer diagnosis based on the Latest Evidence: Where are We?

Exosomes are small extracellular vesicles (EVs) derived from various cellular sources and have emerged as favorable biomarkers for cancer diagnosis and prognosis. These vesicles contain a variety of molecular components, including nucleic acids, proteins, and lipids, which can provide valuable information for cancer detection, classification, and monitoring. However, the clinical application of exosomes faces significant challenges, primarily related to the standardization and scalability of their use. In order to overcome these challenges, sophisticated methods such as liquid biopsy and imaging are being combined to augment the diagnostic capabilities of exosomes. Additionally, a deeper understanding of the interaction between exosomes and immune system components within the tumor microenvironment (TME) is essential. This review discusses the biogenesis and composition of exosomes, addresses the current challenges in their clinical translation, and highlights recent technological advancements and integrative approaches that support the role of exosomes in cancer diagnosis and prognosis.

Integration of liquid biopsy and immunotherapy: opening a new era in colorectal cancer treatment.

Immunotherapy has revolutionized the conventional treatment approaches for colorectal cancer (CRC), offering new therapeutic prospects for patients. Liquid biopsy has shown significant potential in early screening, diagnosis, and postoperative monitoring by analyzing circulating tumor cells (CTC) and circulating tumor DNA (ctDNA). In the era of immunotherapy, liquid biopsy provides additional possibilities for guiding immune-based treatments. Emerging technologies such as mass spectrometry-based detection of neoantigens and flow cytometry-based T cell sorting offer new tools for liquid biopsy, aiming to optimize immune therapy strategies. The integration of liquid biopsy with immunotherapy holds promise for improving treatment outcomes in colorectal cancer patients, enabling breakthroughs in early diagnosis and treatment, and providing patients with more personalized, precise, and effective treatment strategies.

It's high-time to re-evaluate the value of induced-chemotherapy for reinforcing immunotherapy in colorectal cancer.

Immunotherapy has made significant advances in the treatment of colorectal cancer (CRC), revolutionizing the therapeutic landscape and highlighting the indispensable role of the tumor immune microenvironment. However, some CRCs have shown poor response to immunotherapy, prompting investigation into the underlying reasons. It has been discovered that certain chemotherapeutic agents possess immune-stimulatory properties, including the induction of immunogenic cell death (ICD), the generation and processing of non-mutated neoantigens (NM-neoAgs), and the B cell follicle-driven T cell response. Based on these findings, the concept of inducing chemotherapy has been introduced, and the combination of inducing chemotherapy and immunotherapy has become a standard treatment option for certain cancers. Clinical trials have confirmed the feasibility and safety of this approach in CRC, offering a promising method for improving the efficacy of immunotherapy. Nevertheless, there are still many challenges and difficulties ahead, and further research is required to optimize its use.

From organ preservation to selective surgery: How immunotherapy changes colorectal surgery?

The emergence of immunotherapy has revolutionized the traditional treatment paradigm of colorectal cancer (CRC). Among them, immune checkpoint blockade has become the first-line treatment for metastatic colorectal cancer (mCRC) and has made significant progress in the treatment of locally advanced colorectal cancer (LACRC). We reviewed a series of clinical trials that have made breakthrough progress. We will emphasize the breakthrough progress in achieving organ preservation in patients with high microsatellite instability or DNA mismatch repair deficiency (MSI-H/dMMR), and based on this, we propose the concept of selective surgery, which includes selectively removing or preserving lymph nodes, with the aim of proving our idea through more research in the future.

Multifunctional nanocarriers for targeted drug delivery and diagnostic applications of lymph nodes metastasis: a review of recent trends and future perspectives.

Lymph node metastasis is a frequent occurrence in a variety of tumour forms and poses an enormous challenge to cancer treatment. This process is critical to the development of the disease and is frequently linked to a poor prognosis. Over 90% of cancerous cells move through lymph nodes, making them important entry routes for the spread of cancer cells. The prognosis of cancer patients is significantly impacted by lymph node metastases, which also affects treatment choices. Targeting lymph node metastases presents numerous difficulties for conventional medication delivery techniques. It is still very difficult to selectively target cancer cells in lymph nodes without risking injury to healthy organs and unforeseen consequences. Additionally, systemic delivery of drugs is hampered by the slow flow rate of lymphatic vessels. Chemotherapeutic medicines' poor solubility and stability further reduce their effectiveness when taken orally. Additionally, the extracellular matrix that surrounds lymph node tumours is extensive, which makes it difficult for conventional pharmaceutical delivery systems to reach cancer cells. The development of nanocarriers for precise drug delivery to LNs has attracted a lot of interest to overcome these obstacles. Most solid tumours first spread through the lymphatic system, hence effective drug administration to these tissues is essential for better therapeutic results. Nanocarriers have several benefits, including the capacity to pass through barriers like blood-brain barriers and membranes to reach the lymphatic system. High medication dosages can be enclosed thanks to the physicochemical characteristics of nanocarriers, such as their higher surface-to-volume ratio. Additionally, ligands, antibodies, polymers, or biological molecules can be attached to nanocarrier surfaces to change their properties, allowing for the targeted delivery of lymph node epithelial cells. This use of nanocarriers for drug delivery maximizes on-target effects and related adverse effects while improving the effectiveness of medication delivery to target locations. More research and development in this field is needed to optimize nanocarrier design, increase targeting capabilities, and expand clinical applications for better cancer care.

Efficacy of continuous intravenous pumping of insulin for patients with diabetes complicated with perianal abscess and the effect on inflammatory cytokines.

Efficacy of insulin with different administrations for patients with diabetes complicated with perianal abscess and the effect on serum inflammatory cytokines were investigated. One hundred and sixty-seven patients with type 2 diabetes who underwent radical operation of perianal abscess in Jinhua Hospital of Zhejiang University from January 2014 to December 2016 were analyzed. Before and after the operation, 89 patients who received continuous intravenous pumping of insulin for blood glucose control were set as an observation group, and 78 patients who received intermittent subcutaneous injection of insulin as a control group. The operative efficacy, wound healing time and 1-week postoperative growth of the granulation tissue were scored and compared. Fasting blood glucose (FBG) and 2 h postprandial blood glucose (2hPBG) before and after treatment were recorded and compared. Fasting venous blood was extracted before and on the 3rd and 7th days after operation to detect and compare serum inflammatory cytokines including tumor necrosis factor (TNF-α) and interleukin-6 (IL-6). Patients in the observation group had significantly higher total effective rate of the operation than that in the control group (P<0.05), and significantly shorter wound healing time and significantly lower growth score of the granulation tissue (P<0.05). Before treatment, there was no significant difference between the two groups in FBG and 2hPBG (P>0.05). After treatment, FBG and 2hPBG were significantly lower than those before treatment (P<0.050), and FBG and 2hPBG after treatment in the observation group were significantly lower than those in the control group (P<0.05). In conclusion, insulin pumps for injection during the perioperative period of patients with diabetes complicated with perianal abscess can better control the patients' blood glucose, improve the operative efficacy and promote the patients' postoperative healing. Moreover, continuous intravenous pumping of insulin is significantly better than traditional intermittent subcutaneous injection of it in controlling inflammation, so it is worthy of application.

Celastrol inhibits colon cancer cell proliferation by downregulating miR-21 and PI3K/AKT/GSK-3ß pathway.

Celastrol is a traditional Chinese medicine, that is derived from Tripterygium wilfordii. It has been proposed to offer anti-tumor potential. MicroRNAs also play important roles in tumorigenesis. However, the anti-tumor mechanism of Celastrol and whether miRNAs are involved in the process are still unknown. In the present study, MTT assay was used to test the IC50 of Celastrol and cell viability. PCNA, PI3K, Akt, GSK3ß, phosphorylated Akt and GSK3ß were measured by western blotting. Flow cytometry was introduced to detect the apoptosis. We found Celastrol inhibited colon cancer cell viability in a dose-dependent manner companied with PCNA downregulation. Apoptosis was induced by Celastrol. After Celastrol treatment, BCL-2 expression decreased while BAX increased and the Caspase-3 activity was induced. Simultaneously, miR-21 expression was reduced in Celastrol-treated colon cancer cells. miR-21 mimic overexpression could enhance the cell viability, inhibit the apoptosis, decrease BCL-2 expression, increase BAX and induce Caspase-3 activity to some extent which were reversed by Celastrol. In addition, the PI3K/AKT/GSK-3ß pathway was activated by miR-21 mimic but partially arrested by extra-adding Celastrol. Thus, Celastrol may inhibit colon cancer cell proliferation by negatively regulating miR-21 and the PI3K/AKT/GSK-3ß pathway.