Inheritance patterns of leukocyte gene expression under heat stress in F1 hybrid cattle and their parents.

Crossbreeding capitalizes on heterosis effects and results in increased performance of crossbred animals. Dominance hypothesis and overdominance hypothesis are 2 common models proposed to explain heterosis. Differential gene expression between parents and hybrids is hypothesized to be responsible for heterosis. This study aimed to investigate the heat tolerance and inheritance patterns of leukocyte transcriptomics in F1 hybrid cattle (Angus males × Droughtmaster females) and their parents Red Angus (AN) and Droughtmaster (DR) under heat stress. According to the respiratory rate and heat tolerance coefficient index, DR was better adapted to heat stress than AN. The physiological responses to heat stress of F1 hybrids were similar to AN. We identified 802 differentially expressed genes in leukocytes between AN and DR under heat stress using mRNA sequencing. Compared with AN, upregulated genes in DR were enriched in biological processes of response to stress, external and chemical stimulus, and cytokine, cell surface receptor signaling pathway, and cardiovascular system development. In contrast, upregulated genes in AN were enriched in B cell activation and regulation of B cell activation. Gene expression levels can be inherited additively or nonadditively and are classified into additive (35%), dominance (44%), and overdominance and underdominance (18%) modes in F1 hybrids and their parents. Inheritance patterns of gene expression showed that 97% (249/255) of the dominant genes were classified as paternal AN dominant in hybrids. The paternal imprinted PEG10 gene and its regulatory transcription factor MYC showed an AN dominant expression pattern. The MYC interacted with most AN dominant genes. These transcriptomic analyses revealed that DR and AN had specific cellular and humoral immunity and cardiovascular systems development function under heat stress. Inheritance pattern analyses from gene expression partly explained phenotypic differences between parents and F1 hybrids. The paternal imprinted PEG10 gene interaction with transcription factor MYC may contribute to explaining paternal dominant gene expression in hybrids.

Plumbagin inhibits the proliferation of nasopharyngeal carcinoma 6-10B cells by upregulation of reactive oxygen species.

Plumbagin (PLB) is the primary component of the traditional Chinese medicine Baihua Dan, and possesses anti-infection and anticancer effects, with the ability to enhance the sensitivity of tumor cells to radiation therapy. However, the anticancer effect of PLB on nasopharyngeal carcinoma and the underlying mechanisms remain unclear. In this study, we investigated the anticancer effects of PLB on nasopharyngeal carcinoma 6-10B cells and clarified its molecular mechanisms in vitro. The results showed that PLB was effective against 6-10B cells proliferation in a dose-dependent manner by inducing G2/M phase cell cycle arrest. Furthermore, our data showed that PLB induced reactive oxygen species accumulation, which inhibited the GSK3ß/STAT3 pathway and arrested the G2/M phase. Therefore, our results provided new insight into the mechanism of the antitumor effects of PLB, supporting PLB as a prospective therapeutic drug in nasopharyngeal carcinoma by modulating intracellular redox balance.

Tumor Volume Reduction After Gemcitabine Plus Cisplatin Induction Chemotherapy in Locally Advanced Nasopharyngeal Cancer: Comparison with Paclitaxel and Cisplatin Regimens.

BACKGROUND Gemcitabine plus cisplatin (GP) is a novel regimen of induction chemotherapy (IC) for treating locoregional advanced nasopharyngeal cancer (NPC). This retrospective study aimed to compare the efficacy of GP and TP (paclitaxel plus cisplatin) regimens in tumor volume reduction after IC. MATERIAL AND METHODS Between January 2014 and July 2017, 44 patients with III-IVB stage NPC received GP IC followed by concurrent chemoradiotherapy. These patients were matched with 44 patients receiving TP IC according to clinical characteristics. The gross tumor volume of the primary site and positive lymph nodes were delineated by magnetic resonance imaging before and after IC, as well as the nasopharyngeal air cavities. The changes in tumor volume and nasopharyngeal air cavity after IC were calculated and compared between the 2 groups. Treatment toxicities and early survival outcomes were also reported. RESULTS There were no differences in the initial tumor volume and nasopharyngeal cavity between the 2 groups. The volume changes after IC for the primary site, lymph nodes, and nasopharyngeal cavity were 31.4 (range, -0.97-75.8), 4.68 (range, -7.08-22.06), and 2.62 (range, 0.1-7.63) mL for GP and 23.36 (range, -59.14-83.58), 4.7 (range, -11.21-48.61), and 1.47 (range, -2.47-6.17) mL for TP, respectively. All comparisons favored the GP regimen. The toxicities of the 2 regimens were comparable and no survival differences were observed at follow-up (median, 18.7 months). CONCLUSIONS Changes in the tumor volume and nasopharyngeal air cavity showed that the GP regimen was significantly more effective than the TP regimen in tumor burden reduction. However, whether the advantages of GP can translate into survival benefits requires further investigation.

Toripalimab in Combination With Induction Chemotherapy and Subsequent Chemoradiation as First-Line Treatment in Patients With Advanced/Metastatic Esophageal Carcinoma: Protocol for a Single-Arm, Prospective, Open-Label, Phase II Clinical Trial (TR-EAT).

Immune checkpoint inhibitor therapy combined with chemotherapy is safe and effective in treating advanced esophageal carcinoma; however, some patients still experience tumor progression and/or metastasis. Whether the addition of radiotherapy to immunotherapy combined with chemotherapy improves the prognosis of patients with advanced/metastatic esophageal carcinoma needs to be investigated. In the present study, we developed a protocol for our clinical trial indicating that toripalimab combined with induction chemotherapy followed by chemoradiotherapy can safely prolong survival in patients with stage IV esophageal carcinoma. This open-label, single-arm, phase II trial will include patients with unresectable stage IV esophageal squamous cell carcinoma who have not received prior systemic therapy. The patients will be treated with two cycles of toripalimab (240 mg, 1 day before chemotherapy, Q3W) combined with induction chemotherapy (paclitaxel, 135-175 mg/m2 + carboplatin, area under the curve = 4-6, day 1, intravenous, Q3W). Thereafter, they will undergo two cycles of the aforementioned treatment with concurrent radiotherapy (30-50 Gy in 15-25 fractions), followed by toripalimab (240 mg, day 1, Q3W) for 1 year. The primary outcome measure will be progression-free survival; the secondary outcome measures will include the objective response rate, disease control rate, duration of remission, 1- and 2-year overall survival rates, safety and tolerability, and changes in health-related quality of life. The study protocol was approved by the Ethics Committee of Sichuan Cancer Hospital (SCCHEC-02-2021-021). The trial is underway in accordance with the Declaration of Helsinki. Clinical Trial Registration: http://www.chictr.org.cn/showproj.aspx?proj=126830, identifier ChiCTR2100046715.

Tislelizumab Plus Chemotherapy Sequential Neoadjuvant Therapy for Non-cCR Patients After Neoadjuvant Chemoradiotherapy in Locally Advanced Esophageal Squamous Cell Carcinoma (ETNT): An Exploratory Study.

Background: Esophageal squamous cell carcinoma (ESCC) remains a challenging malignant tumor with poor prognosis and limited treatment methods worldwide, and most patients are at a locally advanced stage at diagnosis. High recurrence and metastasis rates remain the main factors leading to the failure of the current standard treatment of neoadjuvant chemoradiotherapy plus surgery for resectable locally advanced ESCC. Improving the pathological complete response (pCR) rate may significantly benefit the survival of patients with resectable locally advanced ESCC after neoadjuvant therapy. Methods: Tislelizumab plus sequential neoadjuvant chemotherapy was administered to non-clinical complete response (cCR) patients after neoadjuvant chemoradiotherapy for locally advanced ESCC. The patients then received surgery and adjuvant therapy according to the postoperative pathological results. Eighty patients with locally advanced ESCC were recruited for the study. The primary outcomes of the pCR rate and the incidence of adverse events will be analyzed completely within 24 months, and the secondary endpoints will include cCR rate, major pathological response rate, objective response rate, R0 resection rate, event-free survival, and overall survival. Discussion: This study explored the safety and efficacy of tislelizumab plus chemotherapy sequential neoadjuvant therapy for non-cCR patients and provided a total neoadjuvant therapy model that can benefit patients with locally advanced ESCC. Clinical Trial Registration: ClinicalTrials. gov NCT05189730. Registered: November 26, 2021, https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S000BBD5&selectaction=Edit&uid=U0004UG3&ts=47&cx=e0cm59.

Enhancing social support and knowledge perception decreases patient delay in breast cancer.

BACKGROUND: Patient delay commonly appears in breast cancer (BC), but the findings for influential factors may be contaminated by recall bias. The real factors in patient delay (divided into appraisal delay and utilization delay) for women with BC urgently need to be objectively analyzed for preventing the progression of this disease. METHODS: Women meeting strict inclusion and exclusion criteria were asked to fill in a questionnaire, which included three sections of sociodemographic characteristics, medical history, and knowledge of BC. Later on, the outcomes were processed according to the verification of BC by pathological diagnosis. Then, multiple linear regression was conducted to analyze the potential factors of the delay and to explore their relations between these factors and BC. RESULTS: Appraisal delay is the leading component of patient delay. Appraisal delay's time distribution of a higher percentage at delay time 0-29 and >360 days, while other delay time occupies lower percentage, which is highly consistent with that of patient delay, while utilization delay mainly occurs in the 0-29 days period. Concerning the influential factors for the different phases of delay, age (P=0.051, P=0.035 separately in appraisal and patient delay), residential address (P=0.036, P=0.010) and symptom disclosure to others (P=0.015, P=0.015) led to a decrease of appraisal and patient delay. However, reasons for first medical consultation (P=0.033, P=0.006) and knowledge of BC (P=0.027, P=0.002) would accelerate appraisal and patient delay. Many factors related to hospitals, such as hospital category for first medical consultation (P=0.030) and examinations for first medical consultation (P=0.055) would reduce utilization delay. CONCLUSIONS: Obstacles in medical consultation for younger women should be removed, and early interventions are needed to avoid progression of BC.

Clinical outcomes for 61 cases of hypopharyngeal cancer with synchronous esophageal cancer.

The aim of this research was to provide data from a single-center study of the treatment of synchronous hypopharyngeal cancer (HPC) and esophageal cancer (EC) with different treatment modalities. A total of 61 patients with synchronous HPC and EC were included in this study. Patients were treated with radiotherapy/chemoradiotherapy (28 cases), surgery (9 cases), palliative radiotherapy and/or chemotherapy (17 cases), or supportive care (7 cases). The median radiotherapy doses for EC and HPC in the radiotherapy/chemoradiotherapy group were 64.5 Gy (range, 0-70) and 70 Gy (range, 60-75.2), respectively. Seven patients in the surgery group received pharyngoesophagectomy with gastric pull-up reconstruction, and two received esophagectomy followed by radiotherapy at the hypopharynx. Cox proportional hazard analysis revealed that the outcome of active treatments, including surgery and radiotherapy/chemoradiotherapy, was better than that of conservative care. In survival analysis, patients in the surgery group tended to have a better 3-year overall survival rate than those in the radiotherapy/chemoradiotherapy group (55.6% vs 30.9%); however, this difference was not statistically different (P = 0.493). The two groups had similar 3-year progression-free survival rates (30.6% and 33.3%, P = 0.420). The current study suggested that radiotherapy/chemoradiotherapy should be considered as an important treatment modality in addition to surgery for synchronous HPC and EC.

Widespread lymph node recurrence of major duodenal papilla cancer following pancreaticoduodenectomy.

Major duodenal papilla cancer (MDPC) represents the primary type of duodenal cancer, and is typically considered a periampullary carcinoma as most tumors arise in this region. This report describes an extremely rare case involving a patient with rapidly and extensively recurrent MDPC following pancreaticoduodenectomy, who achieved complete response by concurrent image-guided radiation and intravenous oxaliplatin plus oral capecitabine therapies. The patient was a 50-year-old female who was admitted to our hospital 6 wk after resection for MDPC for evaluation of a nontender and enlarged node in the left side of her neck. After clinical work-up, the patient was diagnosed with postoperatively recurrent MDPC with widespread lymph node metastases at the bilateral cervix, mediastinum, abdominal cavity, and retroperitoneal area. She was administered whole field image-guided radiation therapy along with four cycles of the intravenous oxaliplatin plus oral capecitabine regimen. A complete response by positron emission tomography with 18-fluorodeoxyglucose was observed 4 months after treatment. The patient continues to be disease-free 2 years after the diagnosis of recurrence.