This study aimed to investigate the clinical and prognostic relevance of B7-H3 expression and indicators of glucose metabolism in patients with colorectal cancer (CRC).
Using immunohistochemistry, ...the expression of B7-H3 was detected in a total of 213 formalin-fixed paraffin-embedded CRC tissue specimens. Furthermore, levels of fasting blood glucose (FBG), lactic dehydrogenase (LDH), and fructosamine (FMN) as indicators of glucose metabolism were analyzed in CRC patients and stratified into high or low expression sub-groups based on Youden Index. The relationship between B7-H3, FBG, LDH, FMN expression, and clinicopathological characteristics were also evaluated to establish their prognostic significance in patients with CRC.
B7-H3 was highly expressed in CRC tissue. The positive rates of B7-H3 expression was 63.8% (136/213). We found a linear correlation between B7-H3 and FBG in depth of tumor invasion (T3/4) (
= 0.037,
= 0.259), lymph node metastasis (N0) (
= 0.004,
= 0.259), and TNM stage (I/II) (
= 0.009,
= 0.242). High expression of FBG, LDH, FMN hazard ratio (HR) = 1.916, 95% CI: 1.223-3.00,
= 0.005; HR = 1.801, 95% CI: 1.153-2.813,
= 0.010; HR = 2.154, 95% CI: 1.336-3.472,
= 0.002, respectively, was identified as a significant independent predictor of poor overall survival (OS). Although B7-H3 expression did not affect OS, CRC patients expressing both high B7-H3 and high FMN contributed to a significant decrease in OS (HR = 1.881, 95%CI: 1.059-3.339,
= 0.031). Moreover, with low expression of B7-H3, high expression of FBG, LDH and FMN were also recognized as predictors of inferior OS (HR = 3.393, 95% CI: 1.493-7.709,
= 0.004; HR = 7.107, 95% CI: 2.785-18.138,
= 0.000; HR = 2.800, 95% CI: 1.184-6.625,
= 0.019).
B7-H3 combined with FBG, LDH, or FMN, could reflect the clinical outcomes of patients with CRC.
Platinum (Pt) derivatives such as cisplatin and carboplatin are the class of drugs with proven activity against triple-negative breast cancer (TNBC). This is due to the ability of Pt compounds to ...interfere with the DNA repair mechanisms of the neoplastic cells. Taxanes have been efficacious against estrogen receptor-negative tumors and act by disruption of microtubule function. Due to their distinct mechanisms of action and routes of metabolism, the combination of the Pt agents and taxanes results in reduced systemic toxicity, which is ideal for treating TNBC. Also, the sensitivity of
-mutated cells to taxanes remains unsolved as
evidence indicates resistance against taxanes due to
mutations. Recent evidence suggests that the combination of carboplatin and paclitaxel resulted in better pathological complete response (pCR) in patients with TNBC, both in neoadjuvant and adjuvant settings.
studies showed sequential dependency and optimal time scheduling of Pt- and taxane-based chemotherapy. Also, combining carboplatin with docetaxel in the NAC regimen yields an excellent pCR in patients with
-associated and wild-type TNBC. TNBC is a therapeutic challenge that can be tackled by identifying new therapeutic sub-targets and specific cross-sections that can be benefitted from the addition of Pt- and taxane-based chemotherapy. This review summarizes the merits as well as the mechanism of Pt- and taxane-based adjuvant and neoadjuvant chemotherapies in early TNBC from the available and ongoing clinical studies.
Luteolin (Lut) is a natural flavonoid polyphenolic compound with multiple pharmacological activities, such as anti-oxidant, anti-inflammatory, and anti-tumor effects. However, the poor aqueous ...solubility and low bioactivity of Lut restrict its clinical translation. Herein, we developed a reactive oxygen species (ROS)-responsive nanoplatforms to improve the bioactivity of Lut. Folic acid (FA) was employed to decorate the nanoparticles (NPs) to enhance its targeting ability. The size of Lut-loaded ROS-responsive nanoparticles (Lut/Oxi-αCD NPs) and FA-modified Lut/Oxi-αCD NPs (Lut/FA-Oxi-αCD NPs) is 210.5 ± 6.1 and 196.7 ± 1.8 nm, respectively. Both Lut/Oxi-αCD NPs and Lut/FA-Oxi-αCD NPs have high drug loading (14.83 ± 3.50 and 16.37 ± 1.47%, respectively). In vitro cellular assays verified that these NPs could be efficiently internalized by 4T1 cells and the released Lut from NPs could inhibit tumor cells proliferation significantly. Animal experiments demonstrated that Lut/Oxi-αCD NPs, especially Lut/FA-Oxi-αCD NPs obviously accumulated at tumor sites, and inhibited tumor growth ∼3 times compared to the Lut group. In conclusion, the antitumor efficacy of Lut was dramatically improved by targeting delivery with the ROS-responsive nanoplatforms.
Breast cancer is a common malignant tumor associated with high morbidity and mortality. The role of ferroptosis, a regulated form of cell death, in breast cancer development and prognosis remains ...unclear. This study aims to investigate the relationship between ferroptosis-related genes and breast cancer and develop a prognostic model.
RNA-seq expression datasets and clinical samples of breast cancer patients were obtained from public databases. Immunity- and drug resistance-related data were integrated. A preliminary screening was performed, resulting in the identification of 73 candidate ferroptosis factors. Univariate Cox regression analysis was conducted to select 12 genes, followed by LASSO Cox regression analysis to construct a prognostic risk prediction model consisting of 10 ferroptosis-related genes. The model was further characterized by immune cell infiltration. The expression levels of ferroptosis-related genes were validated in human breast cancer cell lines, and immunohistochemical (IHC) analysis was conducted on cancer specimens to assess ferroptosis-related protein expression.
The study identified 10 ferroptosis-related genes that were significantly associated with breast cancer prognosis. The constructed prognostic risk prediction model showed potential for predicting the prognostic value of these genes. In addition, the infiltration of immune cells was observed to be a characteristic of the model. The expression levels of ferroptosis-related genes were confirmed in human breast cancer cell lines, and IHC analysis provided evidence of ferroptosis-related protein expression in cancer specimens.
This study provides a novel prognostic model for breast cancer, incorporating 10 ferroptosis-related genes. The model demonstrates the potential for predicting breast cancer prognosis and highlights the involvement of immune cell infiltration. The expression levels of ferroptosis-related genes and proteins further support the association between ferroptosis and breast cancer development.
This self-controlled study aimed to clarify whether indocyanine green (ICG) could be an alternative tracer in the absence of radioisotope (RI) for combined imaging of axillary sentinel lymph node ...(SLN) in breast cancer.
Primary breast cancer, clinically axillary node-negative patients (n = 182) were prospectively enrolled from March 2015 to November 2020. ICG, methylene blue (MB), and RI were used to perform axillary sentinel lymph node biopsy (SLNB). The main observation index was the positivity of ICG + MB vs. RI + MB in axillary SLNB; the secondary observation indicators were the axillary SLN detection rate, mean number of axillary SLNs detected, mean number of metastatic axillary SLNs detected, and safety.
All 182 patients had axillary SLNs; a total of 925 axillary SLNs were detected. Pathological examination confirmed metastatic axillary SLN in 42 patients (total of 79 metastatic SLNs). Positivity, detection rate of SLNs, detection rate of metastatic SLNs, and the number of metastatic SLNs detected were comparable with RI+MB and ICG+MB (
> 0.05). The mean number of axillary SLNs detected was significantly higher with ICG+MB than with RI+MB (4.99 ± 2.42 vs. 4.02 ± 2.33,
0.001). No tracer-related adverse events occurred.
ICG appears to be a safe and effective axillary SLN tracer, and a feasible alternative to RI in combined imaging for axillary SLN of breast cancer.
Although stimuli-responsive nanoplatforms were developed to deliver immunogenic cell death (ICD) inducers to enhance cancer immunotherapy, the complete release of ICD inducers into the tumor ...microenvironment (TME) was limited by the inadequate supplementation of endogenous stimulus (e.g., reactive oxygen species (ROS)). To address this issue, we synthesized a self-responsive nanomaterial with self-supplied ROS, which mainly consists of a ROS responsive moiety HPAP and cinnamaldehyde (CA) as the ROS-generating agent. The endogenous ROS can accelerate the degradation of HPAP in materials to release docetaxel (DTX, an ICD inducer). In intracellular acidic environment, the pH-sensitive acetal was cleaved to release CA. The released CA in turn induces the generation of more ROS through mitochondrial damage, resulting in amplified DTX release. Using this self-cycling and self-responsive nanomaterial as a carrier, DTX-loaded pH/ROS dual-responsive nanoparticles (DTX/FA-CA-Oxi-alphaCD NPs) were fabricated and evaluated in vitro and in vivo. In vitro experiments validated that the NPs could be effectively internalized by FA-overexpressed cells and completely release DTX in acidic and ROS microenvironments to induce ICD effect. These NPs significantly blocked 4T1 cell migration and decreased cell invasion. In vivo experiments demonstrated that the tumor-targeted NPs significantly inhibited tumor growth and blocked tumor metastasis. More importantly, these NPs significantly improved immunotherapy through triggering effector T-cell activation and relieving the immunosuppressive state of the TME. Our results demonstrated that DTX/FA-CA-Oxi-alphaCD NPs displayed great potential in preventing tumor metastasis, inhibiting tumor growth, and improving the efficacy of anti-PD-1antibody.
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► Gold and graphene modified carbon ionic liquid electrode was fabricated. ► ssDNA probe was covalently-linked on the electrode to prepare the DNA biosensor. ► Polymerase chain ...reaction product of Listeria monocytogenes gene was detected.
A new electrochemical DNA biosensor was fabricated by using a dendritic gold nanoparticles and electrochemical reduced graphene (GR) composite modified carbon ionic liquid electrode (CILE) as the platform. Ionic liquid 1-butylpyridinium hexafluorophosphate was used as the binder for the preparation of CILE and GR film was further decorated on the CILE surface by electrochemical reduction. Then the dendritic nanogold was electrodeposited on the surface of GR/CILE to get a modified electrode as Au/GR/CILE, which was further used for the formation of mercaptoacetic acid self-assembling film. The amino modified ssDNA probe sequence was covalently linked with mercaptoacetic acid to get the ssDNA modified electrode for the further hybridization. Methylene blue (MB) was used as the electrochemical indicator for monitoring the hybridization reaction after hybridized with the target ssDNA. Under the optimal conditions the specific Listeria monocytogenes hly ssDNA sequences could be detected by measuring the differential pulse voltammetric responses of the accumulated MB molecules on dsDNA molecules. The linear concentration range was achieved from 1.0×10−12 to 1.0×10−6mol/L with the detection limit as 2.9×10−13mol/L (3σ). This electrochemical DNA sensor exhibited excellent selectivity with the good discrimination ability of one-base and three-base mismatched ssDNA sequences. The polymerase chain reaction product of L. monocytogenes hly gene that extracted from deteriorated fish was successfully detected, which indicated that this electrochemical DNA sensor could be further used for the detection of specific ssDNA sequence in real biological samples.
This randomized study aimed to compare the clinical efficacy between the novel dual tracer composed of indocyanine green (ICG) and blue dye (BD) and the conventional dual tracer composed of ...radioisotope and BD for sentinel lymph node (SLN) mapping in patients with breast cancer.
This study enrolled 471 clinically lymph node-negative patients with primary breast cancer. All patients underwent mastectomy, and those undergoing sentinel lymph node biopsy (SLNB) were randomized to receive blue dye plus radioisotope (RB group) or BD plus ICG (IB group). The detection performances on SLN identification rate, positive SLN counts, detection sensitivity, and false-negative rate were compared between the two groups.
In the IB group, 97% (194/200) of the patients who underwent the ICG and BD dual tracer injection showed fluorescent-positive lymphatic vessels within 2-5 min. The identification rate of SLNs was comparable between the IB group (99.0%, 198/200) and the RB group (99.6%, 270/271) (
= 0.79). No significant differences were observed in the identification rate of metastatic SLNs (22.5%
. 22.9%,
> 0.05, RB group
. IB group, the same below), positive SLN counts (3.72 ± 2.28
. 3.91 ± 2.13,
> 0.05), positive metastatic SLN counts (0.38 ± 0.84
. 0.34 ± 0.78,
> 0.05), SLNB detection sensitivity (94.4%
. 92.5%,
> 0.05), or false-negative rate (5.6%
. 7.5%,
> 0.05) between the two groups.
ICG can be used as a promising alternative tracer for radioisotope in SLN mapping, and when it is combined with BD in lymphangiography, it offers comparable detection sensitivity compared to the conventional lymphatic mapping strategies that are widely used in clinical practice.
To investigate the safety and feasibility of extending the flushing interval for the totally implantable venous access port (TIVAP) during the non-treatment stage in patients with breast cancer (BC) ...by retrospectively analyzing the patients' clinical data, including the incidence of TIVAP-related complications.
This single-center retrospective study included patients with BC who underwent TIVAP implantation at our hospital between January 2018 and March 2021 during their non-treatment phase and visited the hospital regularly for TIVAP flushing. Among the 1013 patients with BC who received TIVAP implantation, 617 patients were finally included on the basis of the inclusion and exclusion criteria and divided into three groups according to the length of the flushing interval: group 1 (≤30 days, n = 79), group 2 (31-90 days, n = 66), and group 3 (91-120 days, n = 472). The basic characteristics of patients in each group and the incidence of TIVAP-related complications (catheter obstruction, infection, and thrombosis) were analyzed.
No significant intergroup differences were observed in age, body mass index (BMI), tumor stage, pathological staging, implantation approach, chemotherapy regimen, duration of treatment, and TIVAP-related blood return rate (P > 0.05). Among patients from all three groups, 11 cases of catheter pump-back without blood and eight cases of TIVAP-related complications such as infection, thrombosis, and catheter obstruction were recorded. However, no significant differences in TIVAP-related complications were observed among the three groups (P > 0.05).
Extending the TIVAP flushing interval beyond three months during the non-treatment stage in BC patients is safe and feasible and did not increase the incidence of TIVAP-related complications.
Serum P1NP, one of the important biomarkers for bone turnover, is commonly used for the prediction of bone fracture and the prognosis of osteoporosis after therapy. We developed a P1NP ...chemiluminescence assay and evaluated changes in bone metabolism markers in lung transplant patients. The screened 2 P1NP antibodies with constructed antigens and α-1 chain antigens expressed by the Corynebacterium glutamate expression system were applied into assay development. The assay performance was evaluated to examine the reliability. A normal Q-Q plot was used to establish male reference interval. Changes of bone metabolism markers before and after lung transplantation in 19 patients were evaluated. The linear factor R of P1NP reagent was greater than 0.99. The limit of detection was 3.32 ng/ml. The precision of the three batches of P1NP reagents was lower than 8%. Method comparison with Roche P1NP reagent showed that the correlation coefficient R2 was 0.91. In the monitoring of bone mass in a short time, bone metabolism markers can better indicate the change of bone mass, while the traditional bone mineral density detection is lagging behind the bone metabolism markers. P1NP and β-CrossLap to bone mass change in patients after lung transplantation, and P1NP and β-CrossLap are very good clinical markers for bone mass monitoring.
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