Colorectal cancer (CRC) is the third most frequently diagnosed cancer and this study aimed to develop a conatumumab decorated, irinotecan prodrug and quercetin co-loaded delivery system for combine...

Background: Immunocheckpoint inhibitor(ICI) is a major breakthrough in tumor treatment. It can activate the patient’s own immune system and play an anti-tumor role, but not all patients can benefit from it. At present, there is still a lack of effective biomarkers to guide clinical application. The systemic immune inflammation(SII) index reflects the systemic inflammatory state and immune state of patients. Prognostic nutrition index(PNI) can be used to evaluate immune status of patients. Therefore, SII and PNI indexes may have some value in predicting the efficacy and prognosis of immunotherapy, but there is still a lack of relevant research. The purpose of our study was to explore the influence of SII and PNI index on the efficacy and prognosis of immunotherapy. Methods: A total of 1935 patients treated with ICIs treatment in the Fourth Hospital of Hebei Medical University from November 2016 to October 2021 were retrospectively collected. 435 patients who met the inclusion criteria and did not meet the exclusion criteria. The imaging data, blood results of each patient were collected within 1 week before ICIs treatment. The neutrophil lymphocyte ratio(NLR), platelet lymphocyte ratio(PLR), monocyte lymphocyte ratio(MLR), PNI,systemic inflammatory response index(SIRI),neutrophil-eosinophil ratio(NER) was calculated. The patients were followed up by in-patient, out-patient reexamination and telephone contact, and the efficacy evaluation and survival status were recorded. The deadline of follow-up: January 2021. SPSS-24.0 software was employed for statistical analysis. Results: Among the 435 patients receiving ICI treatment, 61,236 and 138 patients were evaluated respectively as partial response (PR), stable disease (SD) and progressive disease (PD). The overall response rate(ORR) and disease control rate (DCR) of this cohort were 14.0% and 68.3%, respectively. Median progression-free survival (mPFS) is 4.0 months, The overall survival (mOS) of this cohort is 6.8 months. Multivariate analysis showed that SIRI(Hazard Ratio, HR = 1.304, P = 0.014), PNI (HR = 0.771, P = 0.019), prealbumin (PAB) (HR = 0.596, P = 0.001), and PNI(HR = 0.657, P = 0.008) were independent risk factors for PFS and OS, respectively. Conclusions: Patients with high SIRI value and low PNI value before ICI treatment have shorter PFS. Patients with higher PNI value have better prognosis. Therefore, hematological indicators may become predictors of immunotherapy.

Background: This paper aims to compare the efficacy and safety of recombinant human endostatin combined with chemotherapy in patients with squamous cell lung cancer (SqCLC). Methods: We searched the Cochrane Library, PubMed, Embase, CNKI, Wanfang database, Metstr, VIP, and others and manually searched books and magazines until 2019 for articles about the efficacy and safety of recombinant human endostatin combined with chemotherapy in patients with SqCLC. A second search was conducted on the review literature. According to the criteria of the literature screen, the relevant randomized controlled trials (RCTs) and nonrandomized controlled trials (non-RCTs) of recombinant human endostatin combined with chemotherapy and chemotherapy alone in the treatment of SqCLC were included. After the data were extracted and analyzed, RevMan 5.3 software was used for meta-analysis for the outcome indicators. Then, heterogeneity tests and sensitivity analyses were carried out, and the publication bias of this study was tested in Stata 13.0 software. Six RCTs and eight non-RCTs were included. In total, 821 patients with SqCLC were included. Results: The response rate (RR) was 2.12 (95% CI: 1.57–2.85, p < 0.00001). The disease control rate (DCR) was 2.38 (95% CI: 1.70–3.32, p < 0.00001). The difference between the two groups was statistically significant. Regarding safety, the incidence rates of the adverse reactions cardiotoxicity, leukopenia, thrombocytopenia, and gastrointestinal reactions were not significantly different between the two groups (OR = 1.70, 95% CI: 0.79–3.68; OR = 0.93, 95% CI: 0.61–1.42; OR = 1.08, 95% CI: 0.71–1.64; OR = 0.86, 95% CI: 0.56–1.30, respectively). Conclusion: The combined treatment had a better therapeutic effect than chemotherapy alone. It did not increase the incidence of adverse reactions in the course of treatment.

Purpose: Colorectal cancer (CRC) is the third most common cancer in the world. The purpose of this study was to investigate the role of TNNT2 in the proliferation, migration and invasion of CRC cells and its expression in CRC tissues to better understand the regulatory role of TNNT2 in CRC. Methods: Western blotting (WB) and qPCR were used to detect the expression of TNNT2 in colorectal cancer tissues and paracancerous tissues. CCK-8, colony formation, Transwell and other experiments were used to clarify the role of TNNT2 in the proliferation, migration and invasion of colorectal cancer cells. Changes in TNNT2, EGFR and HER2 mRNA transcription levels were detected by SYBR Real-Time PCR assay, and the effects of TNNT2 overexpression or knockdown on the expression of EGFR, HER2 and EMT-related proteins in CRC cells were determined by WB. TNNT2 and EGFR intreaction was carried out in HCT116 cells by coimmunoprecipitation experiments. Results: The protein and mRNA expression level of TNNT2 in CRC tissues were higher than those in paracancerous tissues. The CCK-8 results suggested that overexpression of TNNT2 significantly promoted the proliferation of HCT116 and RKO cells, and TNNT2 konckdown gets the opposite result; and the colony formation results were the same as tthose of CCK-8 assay. Transwell invasion and migration experiments showed that overexpression of TNNT2 promoted the migration and invasion of HCT116 and PKO cells, and TNNT2 konckdown suppressed the migration and invasion of the these cells. The SYBR Green I real-time PCR method revealed that them RNA levels of TNNT2, EGFR and HER2 in the TNNT2 overexpression group were higher than those in RKO cells. WB showed that overexpressing TNNT2 increased the expression of EGFR and HER2 in HCT16 and RKO cells,decreased the expression of EMT marker E-cadherin, and increased the expression of Vimentin and N-cadherin. Konckdown of TNNT2 decreased the expression of EGFR and HER2, increased the expression of E-cadherin, and decreased the expression of Vimentin and N-cadherin in HCT16 and RKO cells. The immunocoprecipitation experiment showed that there was an interaction between EGFR and TNNT2. Conclusion: TNNT2 can promote the proliferation, invasion and metastasis of colorectal cancer cells. There is an interaction between TNNT2 and EGFR protein. TNNT2 can upregulate EGFR and HER2-related proteins in colorectal cancer cells and promote the occurrence of EMT. Therefore, TNNT2 can promote the invasion and metastasis of CRC cells through the EGFR/HER2/EMT signal axis, suggesting that TNNT2 is a potential target of CRC treatment.

Metaplastic breast cancer (MBC) is a rare disease, and there was rarely reported the treatment after recurrence and metastasis. Here, we report the treatment of an adult patient who suffered from MBC with lung, lymph nodes and left pleura metastasis after radical surgery. The next-generation sequencing result demonstrated that it had tumor mutational burden (TMB) of 12.0 Muts/Mb and microsatellite stability. The patient received sintilimab, an immune checkpoint inhibitor, plus chemotherapy and achieved partial response (PR). This is a report of a good outcome of metastatic MBC achieving 24 months of progression-free survival (PFS) and 39 months of overall survival (OS) with a combination therapy of immune checkpoint inhibitor and chemotherapy. Immuno-chemotherapy may have antitumor activity for relapse MBC. TMB may serve as a potential predictor associated with PD-1 inhibitors in MBC and help clinicians make an optimum treatment strategy.

Background: Lung cancer is the main cause of cancer death in the world, with small-cell lung cancer (SCLC) accounting for about 10–15% of all lung cancers. Although programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors represent a major breakthrough in SCLC treatment, only a minority of patients will benefit and there is still a lack of accurate biomarkers to guide clinical application. Inflammation plays a crucial role in tumorigenesis, tumor development, metastasis, and drug resistance, but there is limited research on the predictive value of these inflammatory indicators in SCLC. The purpose of our study was to determine the influence of prognostic nutritional index (PNI), systemic immune inflammation (SII), and other indexes on the efficacy and prognosis of patients with SCLC treated with PD-1/PD-L1 inhibitors. Methods: A total of 700 patients of SCLC treated with PD-1/PD-L1 inhibitors in the Fourth Hospital of Hebei Medical University from January 2019 to January 2023 were retrospectively analysed. Among these patients, 246 were included after the inclusion and exclusion criteria were applied. The basic clinical data of patients were collected, included age, sex, PD-1 or PD-L1 inhibitors and so on. The neutrophil:lymphocyte ratio (NLR), platelet:lymphocyte ratio (PLR), PNI, SII, and monocyte:lymphocyte ratio (MLR) were calculated. SPSS 27 software was employed for statistical analysis. As of 1st March 2023, all patients had received a post-diagnosis follow-up. The median follow-up time was 11.7 months. Results: Among the 246 patients with SCLC receiving PD-1/PD-L1 inhibitor treatment. the overall response rate and disease control rate were 47.6% and 89.8%, respectively. Median progression-free survival (PFS) and median overall survival (OS) were 9.0 months and 21.4 months, respectively. Multivariate analysis showed that MLR [hazard ratio (HR) =0.631; P=0.01], and platelet (PLT) count (HR =1.641; P=0.009) were independent risk factors for PFS. NLR (HR =0.566, P=0.01) and lactate dehydrogenase (LDH) (HR =0.446; P=0.002) were independent risk factors for OS. Conclusions: Among patients with SCLC treated with PD-1/PD-L1 inhibitors, those with high MLR and low PLT had shorter PFS, whilst patients with high NLR and LDH had a shorter OS. NLR and LDH may be used as prognostic biomarkers patients with SCLC treated with PD-1/PD-L1 inhibitors. The promising clinical application of NLR and LDH in efficacy prognostic indicators and beneficiary selection for SCLC immunotherapy is highlighted.