Platelet Membrane Coated Cu9S8-SNAP for Targeting NIR-II Mild Photothermal Enhanced Chemodynamic/Gas Therapy of Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is a highly aggressive and uncommon subtype of breast cancer with a poor prognosis. It is crucial to prioritise the creation of a nanotherapeutic method that is highly selective and actively targeting TNBC. This study explores a new nanosystem, Cu9S8-SNAP@PM (C-S@P), composed of Cu9S8-SNAP coated with a platelet membrane (PM). The purpose of this nanosystem is to cure TNBC using multimodal therapy. The utilisation of PM-coated nanoparticles (NPs) enables active targeting, leading to the efficient accumulation of C-S@P within the tumour. The Cu9S8 component within these NPs serves the potential to exert photothermal therapy (PTT) and chemodynamic therapy (CDT). Simultaneously, the S-Nitroso-N-Acetylvanicillamine (SNAP) component enables nitric oxide (NO) gas therapy (GT). Furthermore, when exposed to NIR-II laser light, Cu9S8 not only increases the temperature of the tumour area for PTT, but also boosts CDT and stimulates the release of NO through thermal reactions to improve the effectiveness of GT. Both in vitro and in vivo experimental results validate that C-S@P exhibits minimal side effects and represents a multifunctional nano-drug targeted at tumors for efficient treatment. This approach promises significant potential for TNBC therapy and broader applications in oncology.

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.

Preclinical tumor organoid models in personalized cancer therapy: Not everyone fits the mold.

In contrast to conventional cancer treatment, in personalized cancer medicine each patient receives a specific treatment. The response to therapy, clinical outcomes, and tumor behavior such as metastases, tumor progression, carcinogenesis can be significantly affected by the heterogeneous tumor microenvironment (TME) and interpersonal differences. Therefore, using native tumor microenvironment mimicking models is necessary to improving personalized cancer therapy. Both in vitro 2D cell culture and in vivo animal models poorly recapitulate the heterogeneous tumor (immune) microenvironments of native tumors. The development of 3D culture models, native tumor microenvironment mimicking models, made it possible to evaluate the chemoresistance of tumor tissue and the functionality of drugs in the presence of cell-extracellular matrix and cell-cell interactions in a 3D construction. Various personalized tumor models have been designed to preserving the native tumor microenvironment, including patient-derived tumor xenografts and organoid culture strategies. In this review, we will discuss the patient-derived organoids as a native tumor microenvironment mimicking model in personalized cancer therapy. In addition, we will also review the potential and the limitations of organoid culture systems for predicting patient outcomes and preclinical drug screening. Finally, we will discuss immunotherapy drug screening in tumor organoids by using microfluidic technology.

Development of humanized mouse with patient-derived xenografts for cancer immunotherapy studies: A comprehensive review.

Immunotherapy has revolutionized cancer treatment, however, not all tumor types and patients are completely responsive to this approach. Establishing predictive pre-clinical models would allow for more accurate and practical immunotherapeutic drug development. Mouse models are extensively used as in vivo system for biomedical research. However, due to the significant differences between rodents and human, it is impossible to translate most of the findings from mouse models to human. Pharmacological development and advancing personalized medicine using patient-derived xenografts relies on producing mouse models in which murine cells and genes are substituted with their human equivalent. Humanized mice (HM) provide a suitable platform to evaluate xenograft growth in the context of a human immune system. In this review, we discussed recent advances in the generation and application of HM models. We also reviewed new insights into the basic mechanisms, pre-clinical evaluation of onco-immunotherapies, current limitations in the application of these models as well as available improvement strategies. Finally, we pointed out some issues for future studies.

The emerging therapeutic role of mesenchymal stem cells in anthracycline-induced cardiotoxicity.

Mesenchymal stem cell (MSC)-based tissue regeneration therapy has been extensively investigated for cardiac regeneration over the past two decades. Numerous animal and clinical investigations demonstrated the efficacy of various types of MSCs towards myocardial protection and restoration against anthracycline-induced cardiotoxicity (AIC). It has been established that local or systemic administration of MSCs considerably improved the cardiac function, while ameliorating inflammatory responses and myocardial fibrosis. Several factors influence the outcomes of MSC treatment for AIC, including MSC types, dosages, and routes and duration of administration. In this review, we discuss the recent (from 2015 to 2020) experimental and clinical research on the preventive and regeneration efficacy of different types of MSCs (with or without supporting agents) against AIC, as well as the key factors responsible for MSC-mediated cardiac repair. In addition, challenges and future perspectives of MSC-based cardiac regeneration therapy are also outlined.

Monoclonal antibodies and chimeric antigen receptor (CAR) T cells in the treatment of colorectal cancer.

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer deaths worldwide. Besides common therapeutic approaches, such as surgery, chemotherapy, and radiotherapy, novel therapeutic approaches, including immunotherapy, have been an advent in CRC treatment. The immunotherapy approaches try to elicit patients` immune responses against tumor cells to eradicate the tumor. Monoclonal antibodies (mAbs) and chimeric antigen receptor (CAR) T cells are two branches of cancer immunotherapy. MAbs demonstrate the great ability to completely recognize cancer cell-surface receptors and blockade proliferative or inhibitory pathways. On the other hand, T cell activation by genetically engineered CAR receptor via the TCR/CD3 and costimulatory domains can induce potent immune responses against specific tumor-associated antigens (TAAs). Both of these approaches have beneficial anti-tumor effects on CRC. Herein, we review the different mAbs against various pathways and their applications in clinical trials, the different types of CAR-T cells, various specific CAR-T cells against TAAs, and their clinical use in CRC treatment.

Tumor-Associated Macrophages Promote Oxaliplatin Resistance via METTL3-Mediated m6A of TRAF5 and Necroptosis in Colorectal Cancer.

As a third-generation platinum drug, oxaliplatin (OX) is widely used as the first-line chemotherapeutic agent in the treatment of colorectal cancer (CRC). CRC cells acquire resistance to chemotherapy and develop resistance, which is a major challenge for the treatment of advanced CRC. Recent studies have suggested that the therapeutic resistance of tumors is affected by the tumor microenvironment (TME). As a critical role among TME, tumor-associated macrophages (TAMs) play an important role. However, their regulatory mechanism underlying the drug resistance in CRC remains largely unknown. In the present study, we found that the density of macrophages infiltrated into the CRC tissues from OX-resistant patients was significantly higher compared with the OX-sensitive patients. Interestingly, both the total N6-methyladenosine (m6A) RNA content and the expression of its critical methyltransferase METTL3 were increased in the CRC tissues from OX-resistant patients compared with the OX-sensitive patients. Furthermore, we demonstrated that the M2-polarized TAMs enabled the OX resistance via the elevation of METTL3-mediated m6A modification in cells. Through whole-genome CRISPR screening and further validation, we found that TRAF5 contributes to the METTL3-triggered OX resistance in CRC cells. This study unveiled that M2-TAMs were important mediators for the acquisition of OX resistance. Furthermore, we provided evidence that targeting of M2-TAMs and METTL3-mediated m6A modification might be a promising adjuvant therapeutic strategy for CRC patients, especially for OX-resistant CRC patients.

The role of long non-coding RNAs in mediating chemoresistance by modulating autophagy in cancer.

Cancer is a complex process in which protein-coding and non-coding genes play essential roles. Long noncoding RNAs (lncRNAs), as a subclass of noncoding genes, are implicated in various cancer processes including growth, proliferation, metastasis, and angiogenesis. Due to presence in body fluids such as blood and urine, lncRNAs have become novel biomarkers in cancer detection, diagnosis, progression, and therapy response. Remarkably, increasing evidence has verified that lncRNAs play essential roles in chemoresistance by targeting different signalling pathways. Autophagy, a highly conserved process in response to environmental stresses such as starvation and hypoxia, plays a paradoxical role in inducing resistance or sensitivity to chemotherapy agents. In this regard, we reviewed chemoresistance, the role of lncRNAs in cancer, and the role of lncRNAs in chemoresistance by modulating autophagy.

Recent advances in carbohydrate-based cancer vaccines.

Cancer is a complex multifactorial disease for which many promising therapeutic strategies such as immunotherapy are emerging. Malignant cells frequently express aberrant cell surface carbohydrates, which differentiate them from normal "healthy" cells. This characteristic presents a window for the development of synthetic carbohydrate antigen-based cancer vaccines which can be recognized by the immune system and can bring about T cell-dependent immune responses. Antibodies generated against the carbohydrate antigens partake in the inactivation of carbohydrate-decorated cancer cells, by slowing down tumor cell growth and inducing cancer cell apoptosis. Novel synthetic strategies for carbohydrate antigens have led to several synthetic cancer vaccine candidates. In the present review, we describe the latest progress in carbohydrate-based cancer vaccines and their clinical evaluation in various cancers.

Short- and long-term outcomes after conversion of laparoscopic total gastrectomy for gastric cancer: a single-center study.

PURPOSE: Conversion of laparoscopic surgery for colorectal cancer has been fully studied. However, no study has investigated conversion of laparoscopic total gastrectomy for gastric cancer. We evaluated the effect of conversion to open total gastrectomy on short- and long-term outcomes among patients who underwent laparoscopic total gastrectomy for gastric cancer and identified factors predictive of survival. METHODS: A prospective database of consecutive laparoscopic total gastrectomies for gastric cancer was reviewed. Patients who required conversion (converted group) were compared with those who had completed laparoscopic total gastrectomy (completed group). Kaplan-Meier method was used to compare and analyze survival. Univariate and multivariate analyses were performed to identify predictors of poor survival. RESULTS: The conversion rate was 17.4%, and the most common reason for conversion was a locally advanced tumor. Conversion was associated with significantly longer operative time and greater blood loss. No differences were observed in terms of postoperative morbidity or mortality between the converted and completed patients. The converted group had significantly worse 5-year overall survival (OS) and disease-free survival (DFS). Univariate analysis showed that conversion to open total gastrectomy, pathological (p) T4 disease, and pathological N2-N3 disease were significant risk factors for OS and DFS. In multivariate analysis, pT4 cancer was the only independent predictor of DFS and OS. CONCLUSION: Conversion to open total gastrectomy per se was not associated with worse short-term outcomes or worse long-term survival.

Totally Laparoscopic D2 Radical Distal Gastrectomy Using Delta-Shaped Anastomosis: Initial Experience.

BACKGROUND/AIMS: We presented our preliminary clinical data for totally laparoscopic D2 radical distal gastrectomy using delta-shaped anastomosis (TLG-DSA) to evaluate its effectiveness in terms of minimal invasiveness, technical feasibility, and safety for resection of early gastric cancer. METHODOLOGY: Five consecutive patients who underwent TLG-DSA in our institution from October 22th 2013 to November 29th 2013 were enrolled in this study. In all five cases, only laparoscopic linear staplers were used for intra-corporeal anastomosis. RESULTS: There were 3 men and 2 women, with a mean age of 67.6 years and a mean body mass index (BMI) of 21.4. All the patients with early gastric cancer were received TLG-DSA. No postoperative complications were found in all five patients, and no postoperative mortality occurred. CONCLUSIONS: TLG-DSA using laparoscopic linear staplers for early gastric cancer was safe and feasible. Delta-shaped anastomosis is a simple, easy and safe method of intracorporeal gastroduodenostomy.

Totally laparoscopic right colectomy: technique description.

BACKGROUND/AIMS: Total laparoscopic right colectomy (TLRC) with intracorporeal anastomosis is not widely performed as it requires adequate skills and competence in the use of mechanical linear staplers. Here we describe the technique of TLRC for resection for right colon cancer. METHODOLOGY: We have performed TLRC in a patient for right colon cancer. Technique description of TLRC as well as short-term outcomes is reported. RESULTS: A TLRC for the right colon adenocarcinoma has been successfully performed in a male patient. The specimen included 11 lymph nodes, all of which were free of metastasis. CONCLUSIONS: TLRC for right colon cancer was safe and feasible.

Laparoscopic gastrectomy for gastric cancer in China: an overview.

Since its introduction in China in 2000, laparoscopic gastrectomy has shown classical advantages of minimally invasive surgery over open counterpart. Like all the pioneers of the technique, Chinese gastrointestinal surgeons claim that laparoscopic gastrectomy led to faster recovery, shorter hospital stay and more rapid return to daily activities respect to open gastrectomy while offering the same functional and oncological results. There has been booming interest in laparoscopic gastrectomy since 2006 in China. The last decade has witnessed national growth in the application of laparoscopic gastrectomy and yielded a significant amount of scientific data to support its clinical merits and advantages. However, few prospective randomized controlled trials have investigated the benefits of laparoscopic gastrectomy in China. In this article, we make an overview of the current data and state of the art of laparoscopic gastrectomy for gastric cancer in China.

COLORECTAL Polymeric Immunoglobulin Receptor Expression is Correlated with Hepatic Metastasis and Poor Prognosis in Colon Carcinoma Patients with Hepatic Metastasis.

BACKGROUND/AIMS: Increased expression of polymeric immunoglobulin receptor (pIgR) in tumor tissue has been detected in various cancer forms. However, the clinical relevance of pIgR in colon cancer hepatic metastasis remains uncertain. The aim of this study was to assess the prognostic value of pIgR in patients with colon carcinoma hepatic metastasis after hepatic resection. METHODOLOGY: Genome-wide gene expression analysis was used to evaluate the expression of pIgR in cryopreserved tissue from liver metastases of colon cancer and in the corresponding primary colon cancer tissues from one patient with hepatic metastatic colon cancer. pIgR expression was further confirmed by quantitative real-time PCR in cryopreserved primary colon carcinoma and paired hepatic metastasis tissues from 32 patients with hepatic metastatic colon cancer and by immunohistochemistry in paraffin-embedded primary colon carcinoma and paired hepatic metastasis tissues from 136 patients with liver metastasis from colon carcinoma who underwent hepatic resection. The relation between pIgR expression and clinicopathologic factors and long-term prognosis in these 136 patients was retrospectively examined. The prognostic significance of negative or positive pIgR exspression in colon carcinoma hepatic metastasis was assessed using Kaplan-Meier survival analysis and log-rank tests. RESULTS: Positive expression of pIgR was correlated with liver metastasis of colon cancer. Univariate analysis indicated significantly worse overall survival (OS) for patients with a positive pIgR expression in colon carcinoma hepatic metastasis than for patients with a negative pIgR expression. Multivariate analysis showed positive-pIgR in colon carcinoma hepatic metastasis to be an independent prognostic factor for OS after hepatic resection (P = 0.021). CONCLUSIONS: Positive expression of pIgR was statistically significantly associated with poor prognosis of patients with colon carcinoma hepatic metastasis. pIgR could be a novel predictor for poor prognosis of patients with colon carcinoma hepatic metastasis after hepatic resection.

Advancing non-small cell lung cancer treatment: the power of combination immunotherapies.

Non-small cell lung cancer (NSCLC) remains an unsolved challenge in oncology, signifying a substantial global health burden. While considerable progress has been made in recent years through the emergence of immunotherapy modalities, such as immune checkpoint inhibitors (ICIs), monotherapies often yield limited clinical outcomes. The rationale behind combining various immunotherapeutic or other anticancer agents, the mechanistic underpinnings, and the clinical evidence supporting their utilization is crucial in NSCLC therapy. Regarding the synergistic potential of combination immunotherapies, this study aims to provide insights to help the landscape of NSCLC treatment and improve clinical outcomes. In addition, this review article discusses the challenges and considerations of combination regimens, including toxicity management and patient selection.

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.

Recent advances in biomaterials based near-infrared mild photothermal therapy for biomedical application: A review.

Mild photothermal therapy (MPTT) generates heat therapeutic effect at the temperature below 45 °C under near-infrared (NIR) irradiation, which has the advantages of controllable treatment efficacy, lower hyperthermia temperatures, reduced dosage, and minimized damage to surrounding tissues. Despite significant progress has been achieved in MPTT, it remains primarily in the stage of basic and clinical research and has not yet seen widespread clinical adoption. Herein, a comprehensive overview of the recent NIR MPTT development was provided, aiming to emphasize the mechanism and obstacles, summarize the used photothermal agents, and introduce various biomedical applications such as anti-tumor, wound healing, and vascular disease treatment. The challenges of MPTT were proposed with potential solutions, and the future development direction in MPTT was outlooked to enhance the prospects for clinical translation.

Exosomes-based immunotherapy for cancer: Effective components in the naïve and engineered forms.

Today, cancer treatment is one of the main challenges for researchers. The main cause of tumor cell formation is mutations that lead to uncontrolled proliferation and inhibition of apoptosis in malignant cells. Tumor cells also create a microenvironment that can suppress the immune system cells' responses through various methods, including producing soluble factors and cell-to-cell communication. After being produced from tumor cells, exosomes can also affect the functions of other cells in this microenvironment. Various studies have shown that exosomes from different sources, including tumor cells and immune cells, can be used to treat cancers due to their characteristics. Since tumor cells are rich sources of various types of tumor peptides, they can induce anti-tumor responses. Immune cells also produce exosomes that mimic the functions of their cells of origin, such that exosomes derived from NK cells and CTLs can directly lead to their apoptosis after merging with tumor cells. However, many researchers have pointed out that naïve exosomes have a limited therapeutic function, and their therapeutic potential can be increased by manipulating and engineering them. There are various methods to modify exosomes and improve their therapeutic potential. In general, these methods are divided into two parts, which include changing the cell of origin of the exosome and encapsulating the exosome to carry different drugs. In this review, we will discuss the studies on the therapeutic use of naive and engineered exosomes and provide an update on new studies in this field.

An engineered self-biomineralized oncolytic adenovirus induces effective antitumor immunity and synergizes with immune checkpoint blockade.

Oncolytic adenoviruses (oADV) are promising cancer treatment agents. However, in vivo hepatic sequestration and the host immunological response against the agents limit the therapeutic potential of oADVs. Herein, we present a combined, rational design method for improving oADV infection efficiency, immunogenicity, and treatment efficacy by self-biomineralization. We integrated the biomimetic nucleopeptide W6p into the capsid of oADV using reverse genetics, allowing calcium phosphate mineralization to be biologically induced on the surface of oADV under physiological conditions, resulting in a mineral exterior. This self-biomineralized, modified oADV (oADV-W6-CaP) enhanced infection efficiency and therapeutic efficacy in coxsackie and adenovirus receptor (CAR)-negative cancer cells while protecting them against neutralization by pre-existing neutralizing antibodies. In subcutaneous mouse tumor models, systemic injection of oADV-W6-CaP demonstrated improved antitumor effectiveness, which was associated with increased T-cell infiltration and CD8+ T-cell activation. In addition, the anticancer immune response elicited by oADV-W6-CaP was dependent on CD8+ T cells, which mediated long-term immunological memory and systemic antitumor immunity against the same tumor. Finally, the addition of PD-1 or CD47 inhibition boosted the anticancer effects of oADV-W6-CaP and raised the rate of complete tumor clearance in tumor-bearing animals. The self-biomineralized oADV shifted the suppressive tumor microenvironment from a "cold" state to a "hot" state and synergized with immune checkpoint blockade to exert outstanding tumoricidal effects, demonstrating promising potential for cancer immunotherapy.

Novel immunotherapies for breast cancer: Focus on 2023 findings.

Immunotherapy has emerged as a revolutionary approach in cancer therapy, and recent advancements hold significant promise for breast cancer (BCa) management. Employing the patient's immune system to combat BCa has become a focal point in immunotherapeutic investigations. Strategies such as immune checkpoint inhibitors (ICIs), adoptive cell transfer (ACT), and targeting the tumor microenvironment (TME) have disclosed encouraging clinical outcomes. ICIs, particularly programmed cell death protein 1 (PD-1)/PD-L1 inhibitors, exhibit efficacy in specific BCa subtypes, including triple-negative BCa (TNBC) and human epidermal growth factor receptor 2 (HER2)-positive cancers. ACT approaches, including tumor-infiltrating lymphocytes (TILs) and chimeric antigen receptor (CAR) T-cell therapy, showed promising clinical outcomes in enhancing tumor recognition and elimination. Targeting the TME through immune agonists and oncolytic viruses signifies a burgeoning field of research. While challenges persist in patient selection, resistance mechanisms, and combination therapy optimization, these novel immunotherapies hold transformative potential for BCa treatment. Continued research and clinical trials are imperative to refine and implement these innovative approaches, paving the way for improved outcomes and revolutionizing the management of BCa. This review provides a concise overview of the latest immunotherapies (2023 studies) in BCa, highlighting their potential and current status.