Boron neutron capture therapy (BNCT) is a binary modality that is used to treat a variety of malignancies, using neutrons to irradiate boron-10 (¹⁰B) nuclei that have entered tumor cells to produce highly linear energy transfer (LET) alpha particles and recoil ⁷Li nuclei (¹⁰B [n, α] ⁷Li). Therefore, the most important part in BNCT is to selectively deliver a large number of ¹⁰B to tumor cells and only a small amount to normal tissue. So far, BNCT has been used in more than 2000 cases worldwide, and the efficacy of BNCT in the treatment of head and neck cancer, malignant meningioma, melanoma and hepatocellular carcinoma has been confirmed. We collected and collated clinical studies of second-generation boron delivery agents. The combination of different drugs, the mode of administration, and the combination of multiple treatments have an important impact on patient survival. We summarized the critical issues that must be addressed, with the hope that the next generation of boron delivery agents will overcome these challenges.

Using updated National Health and Nutrition Examination Survey (NHANES) follow-up data, and a large nationwide representative sample of adult U.S. citizens, the aim of this study was to explore the relationship between dietary flavonol intake, all-cause and cause-specific mortality risks. In this prospective cohort study based on NHANES (2007–2008, 2009–2010, and 2017–2018), a total of 11,679 participants aged 20 years and above were evaluated. The amount and type of food taken during a 24-h dietary recall were used to estimate dietary flavonol intake, which includes total flavonol, isorhamnetin, kaempferol, myricetin, and quercetin. Each analysis of the weighted data was dealt with in accordance with the NHANES reporting requirements' intricate stratification design. The Cox proportional risk regression model or Fine and Gray competing risks regression model were applied to evaluate all-cause and cause-specific mortality risks, respectively. The follow-up period was calculated using the time interval between the baseline and the death date or December 31, 2019 (whichever occurs first). Each data analysis was performed between October 1, 2023, and October 22, 2023. Dietary flavonol intake included total flavonol, isorhamnetin, kaempferol, myricetin, and quercetin. Up to December 31, 2019, National Death Index (NDI) mortality data were used to calculate mortality from all causes as well as cause-specific causes. A total of 11,679 individuals, which represents 44,189,487 U.S. non-hospitalized citizens, were included in the study; of these participants, 49.78% were male (n = 5816), 50.22% were female (n = 5, 863); 47.56% were Non-Hispanic White (n = 5554), 18.91% were Non-Hispanic Black (n = 2209), 16.23% were Mexican American (n = 1895), and 17.30% were other ethnicity (n = 2021); The mean [SE] age of the sample was 46.93 [0.36] years, with a median follow-up of 7.80 years (interquartile range, 7.55–8.07 years). After adjusting covariates, Cox proportional hazards models and fine and gray competing risks regression models for specific-cause mortality demonstrated that total flavonol intake was associated with all-cause (HR 0.64, 95% CI 0.54–0.75), cancer-specific (HR 0.45, 95% CI 0.28–0.70) and CVD-specific (HR 0.67, 95% CI 0.47–0.96) mortality risks; isorhamnetin intake was associated with all-cause (HR 0.72, 95% CI 0.60–0.86), and cancer-specific (HR 0.62, 95% CI 0.46–0.83) mortality risks; kaempferol intake was associated with all-cause (HR 0.74, 95% CI 0.63–0.86), and cancer-specific (HR 0.62, 95% CI 0.40–0.97) mortality risks; myricetin intake was associated with all-cause (HR 0.77, 95% CI 0.67–0.88), AD-specific (HR 0.34, 95% CI 0.14–0.85), and CVD-specific (HR 0.61, 95% CI 0.47–0.80) mortality risks; quercetin intake was associated with all-cause (HR 0.66, 95% CI 0.54–0.81), cancer-specific (HR 0.54, 95% CI 0.35–0.84), and CVD-specific (HR 0.61, 95% CI 0.40–0.93) mortality risks; there was no correlation observed between dietary flavonol intake and DM-specific mortality. According to the current study, all-cause, AD, cancer, and CVD mortality risks declined with increased dietary flavonoid intake in the U.S. adults. This finding may be related to the anti-tumor, anti-inflammatory, and anti-oxidative stress properties of flavonol.

PIK3CA gene mutations have been identified in various malignancies, but the prevalence of specific mutations and their role in breast cancer development remain uncertain. This study aimed to investigate the clinicopathological significance and prognostic impact of PIK3CA mutations in breast cancer. Five common PIK3CA mutations (H1047R and H1047L in exon 20, and E542K, E545K, and E545D in exon 9) were identified in breast cancer patients using amplification refractory mutation system (ARMS) allele-specific PCR. The study examined the relationships between these mutations and clinicopathologic factors, such as age, HR status, Her2 status, lymph node involvement, distant metastasis, clinicopathologic stage, and progression-free survival (PFS). A total of 40 female breast cancer patients were included in this study. Twenty mutations were detected, with 12 located in exon 20 and 8 in exon 9. The most frequent mutation was H1047R in exon 20, present in 11 patients (14.8%). PIK3CA mutations were more commonly observed in patients with HR + breast cancer (P < 0.05). No significant correlation was found between PIK3CA mutations and age, Her2 status, lymph node involvement, distant metastasis, clinicopathologic stage, or Ki-67 expression. Database analysis from the cBioPortal online database showed that the median PFS (95%CI) of the PIK3CA unaltered group [22.93 (17.25–48.30) months] was higher than that of the altered group [12.98 (8.18–18.14) months]. In this study, PIK3CA mutant-type group [13.00 (10.56–15.45) months] had lower median PFS than that of the wild-type group [25.00 (13.46–36.55) months] in all breast cancer patients, the difference was significant (P = 0.004). Further, compared with PIK3CA wild-type, mutant-type was associated with poor PFS in HR + and Her2 + breast cancer patients (P < 0.05). In addition, positive H1047R mutation in PIK3CA was associated with poor PFS of breast cancer (P < 0.05). Our data and public database research show that the PIK3CA mutation is a significant gene change in breast cancer, and the PIK3CA mutation was associated with a shorter PFS in all, HR + and Her2 + breast cancer patients. This research confirmed the important role of PIK3CA in breast cancer.

Objective: To explore the correlation between HER-2 status and pathological complete response (pCR) in HER-2-positive breast cancer after dual anti-HER-2 neoadjuvant therapy with trastuzumab and pertuzumab.Methods: A total of 57 HER-2-positive breast cancer patients admitted to the Second Affiliated Hospital of Anhui Medical University and Xijing Hospital Affiliated to Air Force Military Medical University, between January 1, 2019 and September 30, 2020, were enrolled in this multicenter retrospective study. HER-2 status, including HER-2/CEP17 ratio and HER-2/cell number ratio, was detected by FISH. The correlation between HER-2 status/clinicopathological data and pCR was analyzed. The ROC curve was drawn to determine the cutoff value.Results: IHC assessment revealed 40 (70.18%) patients with IHC 3+ and 17 (29.82%) with IHC 2+. 41/57 (71.93%) patients achieved pCR. FISH revealed that the ratio of HER-2/chromosome 17 centromere (HER-2/CEP17) (p<0.001) and the ratio of HER-2/cell number (p<0.001) was significantly correlated with the pCR rate. ROC analysis showed that patients with an HER-2/CEP17 ratio ≥4.495 or HER-2/cell number ≥11.650 have a high pCR rate after dual anti-HER-2 neoadjuvant therapy, suggesting its predictive significance.Conclusion: The response to dual-targeted neoadjuvant therapy with trastuzumab and pertuzumab was adequate in hormone receptor-negative, HER-2-positive breast cancer patients. HER-2/CEP17 ratio and HER-2/cell number ratio were crucial for predicting efficacy.

Background Pertuzumab is a humanized monoclonal antibody for the treatment of breast cancer. HLX11 is a biosimilar of pertuzumab developed by Shanghai Henlius Biotech, Inc. We conducted a bioequivalence study for HLX11 and pertuzumab (United States [US]-, European Union [EU]-, and China [CN]-approved products). Objectives This study compared the biosimilarity in pharmacokinetics (PK), safety, and immunogenicity between HLX11 and reference pertuzumab (approved in the US, the EU, and CN) in healthy Chinese male participants after a single infusion and further characterized the PK profile of HLX11. Methods Eligible individuals were randomized 1:1:1:1 to receive a single dose of 420 mg HLX11, US-, EU-, or CN-pertuzumab via intravenous infusion over 60 min. The primary endpoints were maximum serum drug concentration (C_max), area under the serum concentration–time curve (AUC) from time 0 to time of the last quantifiable concentration (AUC_0–t), and AUC from time 0 to infinity (AUC_0–∞). PK bioequivalence was established if the 90% confidence intervals (CIs) of the geometric mean ratios of the primary endpoints were between 80.0 and 125.0%. Secondary endpoints included other PK parameters, safety, and immunogenicity. Results A total of 160 participants were enrolled and randomly assigned to each group (n = 40 per group). The 90% CIs of the geometric mean ratios of the primary endpoints were all within the prespecified equivalence margins (HLX11 vs. pertuzumab [US-, EU-, CN-approved products]: C_max 97.03–115.06%, 91.39–109.80%, 94.53–110.65%; AUC_0–t 87.65–99.68%, 87.07–100.79%, 86.29–101.09%; AUC_0–∞ 87.66–99.90%, 87.54–101.05%, 89.23–103.20%). The incidence of adverse drug reactions was comparable across the four groups. The presence of anti-drug antibodies or neutralizing antibodies had no obvious effect on PK. Conclusion The PK, safety, and immunogenicity of HLX11 were highly similar to those of reference pertuzumab (US-, EU-, CN-approved products). The established bioequivalence supports further clinical trials of HLX11 in cancer treatment. Trial Registration This study was registered with ClinicalTrials.gov (NCT04411550) and Chinadrugtrials.org.cn (CTR20200618).

Background: Adipocytokines were known to play a relevant role in metabolism, inflammation responses and carcinogenesis of several malignancies. Our aims were to detect the expression of serum adipocytokines, explore their potential diagnostic ability and relationship with clinicopathological characteristics of lung cancer. Methods: Adipocytokines, insulin-like growth factor binding protein 1 (IGFBP-1), resistin, tumor necrosis factors (TNF alpha), TNF RI and TNF RH, vascular endothelial growth factor (VEGF), leptin, interleukin (IL)-6 and IL-10, chemerin, brain-derived neurotrophic factor (BDNF), plasminogen activator inhibitor-1 (PAI-1) were assessed in 49 untreated lung cancer patients and 20 healthy controls. The protein chip was used to detect the serum levels of adipocytokines. Results: Lung cancer patients exhibited significantly elevated serum IGFBP-1, TNF RI, VEGF, TNF RII, PAI-1 and IL-6 levels compared to controls (P<0.05) and most of these adipocytokines revealed a modest discriminative ability for the diagnosis of lung cancer, while BDNF were lower in patients (P<0.05). TNF RI was associated with distant metastasis of lung cancer, while there was no relation between other adipocytokines and the patient clinicopathological features. Conclusions: These results suggest that cytokines IGFBP-1, TNF RI, VEGF, TNF RH, PAI-1 and IL-6 may be involved in the development and progression of lung cancer, and TNF RI may be involved in distant metastasis of lung cancer. Additionally, IGFBP-1, TNF RI, VEGF and TNF RII probably represent potentially useful biomarkers for the diagnosis of lung cancer.