The effect of radiotherapy time and dose on acute hematologic toxicity during concurrent postoperative chemoradiotherapy for early high-risk cervical cancer.

Objective: This study aims to analyze the characteristics and factors that influence acute hematological toxicity (HT) during concurrent chemoradiotherapy (CCRT) for cervical cancer, as well as to provide reference data for clinical practice. Methods: Patients with FIGO IB1-IIA2 cervical cancer who underwent CCRT from May 2018 to August 2020 were included in this study retrospectively. All patients had received external beam radiation therapy and platinum-based concurrent chemotherapy. HT was assessed according to CTCAE 5.0. The pelvic bone marrow was redrawn on the original CT images and divided into four parts: the whole pelvic bone marrow (WP-BM), iliac bone marrow (IL-BM), lower pelvic bone marrow (LP-BM), and lumbosacral bone marrow (LS-BM). The radiation dose and volume of each part of the pelvic bone marrow were recalculated in a new plan created using the original planning parameters. The corresponding dose-volume histogram (DVH) was generated to obtain the bone marrow volumes receiving 10Gy, 20Gy, 30Gy, 40Gy, 45Gy, and 50Gy. Results: In 112 patients, the incidences of grade 2 or higher leukopenia, anemia, thrombocytopenia, and neutropenia were 49.1%, 2.7%, 1.8%, and 20.5%, respectively. Leukopenia was linked to LS-V20 (r = -0.310; P = 0.006) and radiotherapy treatment lengths (days) (r = -0.416; P = 0.013). Anemia was associated with WP-V30, WP-V40, WP-V45, WP-V50, IL-V20, IL-V40, ILV45, IL-V50, LP-V30, LP-V40, LP-V45, and LP-V50 (P <0.05). Thrombocytopenia (r = -0.304, P = 0.007) and neutropenia (r = -0.368, P = 0.009) was associated only with the length of radiotherapy treatment (day). Multiple regression analysis showed that only anemia was negatively correlated with WP-V30, IL-V40, and LP-V40 (P <0.05). Conclusions: Acute HT during CCRT in early-stage high-risk cervical cancer may be related to the duration of radiotherapy and the volume of different radiotherapy doses received at different parts in the pelvic bone marrow.

Soybean balanced the growth and defense in response to SMV infection under different light intensities.

Light is essential for the growth and defense of soybean. It is not clear how soybeans adjust their defenses to different light environments with different cropping patterns. The mechanism of soybean response to Soybean mosaic virus (SMV) infection under different light intensities was analyzed by RNA-seq sequencing method. Enrichment analysis illustrated that most defense-related genes were down-regulated in the dark and the shade, and up-regulated under hard light and normal light. Soybean can resist SMV infection mainly by activating salicylic acid signaling pathway. Light is essential for activating salicylic acid defense signaling pathways. With the increase of light intensity, the oxidative damage of soybean leaves was aggravated, which promoted the infection of virus. When light was insufficient, the growth of soybean was weak, and the plant-pathogen interaction pathway, MAPK pathway and hormone defense pathway in infected soybean was inhibited. Under hard light, some defense genes in infected soybean were down-regulated to reduce the degree of oxidative damage. The expression of differentially expressed genes was verified by real-time fluorescence quantitative RT-PCR. In order to adapt to the change of light intensity, soybean balanced allocation of resources between growth and defense through a series regulation of gene expression. The results of this study will provide a theoretical basis for the research of SMV resistance in intercropping soybean.

[Prenatal diagnosis of a fetus with chromosome 18p deletion and duplication].

OBJECTIVE: To assess the value of chromosomal microarray analysis (CMA) to verify a fetus with partial 18p deletion signaled by non-invasive prenatal testing. METHODS: G-banding chromosomal karyotyping analysis was carried out on amniotic fluid sample of the fetus and peripheral blood samples from the parents. Amniotic DNA was also subjected to CMA analysis. The fetus was also subjected to systematic ultrasound scan. RESULTS: The fetus was found to have a karyotype of 46,XX,18p+. CMA has revealed a 5 Mb deletion at 18p11.32-p11.31, a 2.9 Mb duplication at 18p11.31-p11.23, and a 2.5 Mb duplication at 18p11.23-p11.22. No chromosomal aberration or microdeletion/microduplication was detected in either parent. CONCLUSION: Non-invasive prenatal testing and CMA are both sensitive for the detection of chromosomal microdeletions and microduplications. CMA can help with clarification of genotype-phenotype correlation and facilitate prenatal diagnosis and genetic counseling for the family.

Bone Metastases Pattern in Newly Diagnosed Metastatic Nasopharyngeal Carcinoma: A Real-World Analysis in the SEER Database.

OBJECTIVE: To evaluate the prevalence rate and survival situation of bone metastases in initial nasopharyngeal carcinoma (NPC) patients and the hazard and forecast elements of bone metastases NPC patients. Patients and Methods. The data collected from Surveillance, Epidemiology, and End Results (SEER) program between 2010 and 2016 were evaluated. Univariate and multivariable logistic analysis and the Cox regression were carried out to estimate predictors and elements of the being of bone metastases at diagnosis, respectively. The overall survival of different subgroups were appraised by log-rank tests and the Kaplan-Meier analysis. RESULTS: Factors including male sex, higher N stage, presence of liver, and brain or lung metastases were largely related to the occurrence of bone metastases. The median survival time for bone metastasis NPC patients was 14.0 months. A factor of more than one primary sequence number predicted worse survival. CONCLUSION: The data offer corresponding risks and prognostic indicators of bone metastases for NPC patients.

Oncologic outcomes of pre- versus post-operative radiation in Resectable soft tissue sarcoma: a systematic review and meta-analysis.

BACKGROUND: Postoperative radiation therapy for soft tissue sarcomas demonstrated good local recurrence-free survival rates and survival outcomes. However, the results remained controversial. This study aimed to evaluate the role of preoperative and postoperative radiation therapy for the treatment of resectable soft tissue sarcomas. METHODS: The electronic database PubMed, MEDLINE, Cochrane Library, and EMBASE were performed from inception till 30 November, 2019. The effect of preoperative versus postoperative radiation therapy on resectable soft tissue sarcomas was compared and then assessed. RESULTS: A total of 15 studies with 12,813 patients were included, and most of these had acceptable quality scores. Of these, 10 studies reported data on local recurrence. The pooled results indicated no significant differences between preoperative radiotherapy and postoperative radiotherapy groups for local recurrence, with a risk ratio (RR) and 95% confidence interval (CI) of 0.84 (95%CI = 0.58-1.21). No difference was observed in the overall survival and distant metastasis between the two groups. According to the pooled results, preoperative radiotherapy group showed a significant risk for complications (RR = 2.11, 95%CI = 1.36-3.27). CONCLUSIONS: The postoperative radiation therapy does not increase the local recurrence, overall survival, and distant metastasis, but might result in lowering complications.

Analysis of Clinical Target Volume Delineation in Local-regional Failure of Nasopharyngeal Carcinoma after Intensity-modulated Radiotherapy.

OBJECTIVE: To analyze the pattern of local failure in patients with nasopharyngeal carcinoma (NPC) after intensity-modulated radiotherapy (IMRT) and find a more reasonable delineation of the clinical target volume (CTV). METHODS AND MATERIALS: A total of 212 patients with non-metastatic NPC who underwent IMRT were analyzed. Radiation therapy was run at a total dose of 66-74 Gy (2.0-2.2 Gy fractions). The follow-up of local recurrence and the recurrence-related features were analyzed for the original treatment situation. The failures were delimited as "in-field failure" if Vrecur within the 95% isodose curve (V95%) was ≥95%; "marginal failure" if V95% was less than 95% and not less than 20%; or "out-field failure" if V95% was< 20%. Kaplan-Meier method was used to calculate the survival rates. RESULTS: The median follow-up was 43.4 months. The 5-year local relapse-free survival and overall survival rates were 85.6 and 77.8%, respectively. A total of 18 patients have relapsed. The in-field failure, marginal failure, and out-field failure accounted for 83.3%, 11.1%, and 5.6%, respectively. The site of recurrence was basically in the high dose area. CONCLUSION: These findings suggested that IMRT provide a good local control for patients with NPC, and the in-field failure is the main mode. A wide range of CTV cannot prevent the local recurrence, narrowing the CTV to protect the adjacent organs should be taken into consideration.

Efficacy and Side Effects of Combined Capecitabine Plus Intensity Modulated Radiotherapy as an Effective Adjuvant Therapy for Gastric Cancers.

This study aims to evaluate the clinical outcomes and the toxicities associated with intensity modulated radiotherapy (IMRT) administered in combination with capecitabine for gastric cancer. This study was conducted between July 2009 and October 2011, and included 31 patients (23 female and eight male patients; mean age: 57 years old) with pathologically confirmed gastric cancer (pathological staging T3 or T4 or positive lymph node). All patients underwent D2 surgery and adjuvant chemoradiotherapy, followed by combined treatment with IMRT and capecitabine. All patients received follow-up examinations every 3-6 months by physical examination, magnetic resonance imaging (MRI), and assays for tumor markers. The Kaplan-Meier method was used to calculate the rates for locoregional control (LRC) and disease-free survival (DFS). Only two patients could not complete the planned treatment regimen. Patients treated with IMRT and capecitabine tolerated their treatment well, and displayed few significant side effects. The mean follow-up, disease-free survival (DFS) and survival times were 33.0, 27.5, and 32.9 months, respectively.This study confirmed that the combined administration of IMRT and capecitabine can be used as an adjuvant therapy for gastric cancer patients, with few toxic side effects.

A Novel Radiotherapy Approach for Keloids with Intrabeam.

BACKGROUND: Keloids are hard nodules or plaques formed by excessive proliferation of connective tissue. Radiotherapy, widely used in various benign and malignant skin diseases, is an effective treatment for keloids. This work evaluates Intrabeam photon radiotherapy in the management of keloids. METHODS: Fourteen patients who have undergone Intrabeam radiotherapy for a total of 15 sites of keloids were followed up. Twelve cases were first onset and the other two had recurrent diseases. Thirteen patients underwent surgical resection of keloids before radiotherapy. One relapsing patient received only 2 rounds of radiation therapy as she could not be reoperated. Radiotherapy was divided into 2 sessions on days 0 and 3 after surgery. The dose was 4 or 5 Gy each time for 3 min 14 s to 12 min 1 s. In addition, we compared our data to the recurrence of keloids in fourteen patients who had previously been exposed to electron beam using conventional accelerators. RESULTS: We analyzed the treatment for adverse reactions and recurrence. In the Intrabeam group, one patient developed superficial skin ulcers a month after treatment. No one experienced wound rupture, bleeding, infection, skin contractures, or obvious hyperpigmentation. None of the fourteen cases showed any recurrence so far after on median 22.5 months of follow-up. Five patients in the electron beam group relapsed 3 to 10 months after treatment. CONCLUSION: Here, Intrabeam photon radiotherapy was shown to be an effective treatment for keloid scars and it is therefore recommended for management of this disease.

[Genetic analysis and prenatal diagnosis for a pedigree affected with X-linked Norrie disease].

OBJECTIVE: To detect mutation of NDP gene in a pedigree affected with Norrie disease. METHODS: Sanger sequencing was used to analyze the NDP gene at Xp11.3. Prenatal diagnosis was performed on amniotic fluid sample after the causative gene was detected. RESULTS: Sanger sequencing has revealed a c.2T>C (p.M1T) missense mutation of the NDP gene in the proband and the fetus. The same variation was not found in ClinVar and HGMD database. CONCLUSION: The c.2T>C mutation of the NDP gene probably underlies the Norrie disease in this pedigree.

Chaperonin-containing T­complex protein 1 subunit 8 promotes cell migration and invasion in human esophageal squamous cell carcinoma by regulating α-actin and ß-tubulin expression.

The chaperonin-containing T­complex protein 1 (CCT) has eight subunits, CCT 1-8, which are dysregulated in several types of cancer. To determine how subunit 8 (CCT8) influences the development of esophageal squamous cell carcinoma (ESCC), immunohistochemistry and western blot analysis were performed on 128 ESCC samples in the present study to measure the expression of CCT8. The prognostic value of CCT8 was analyzed using univariate and multivariate survival analyses. CCT8 knockdown in ESCC cells was performed and subsequently, the migration and invasion of ESCC cells was assessed. The results of immunohistochemistry and western blot analysis of ESCC tissue indicated that the expression of CCT8 in tumor tissues from patients with lymph node metastasis (LNM) was high whereas its expression in tissues from those without LNM was low. In addition, the overall survival rate of patients with high CCT8 expression was poor. It was demonstrated that CCT8 influenced the migration and invasion of ESCC cells by regulating α-actin and ß-tubulin. Following CCT8 knockdown, cells were treated with cisplatin; it was demonstrated that α-actin and ß-tubulin were downregulated and that cell apoptosis was enhanced. These data confirm that α-actin and ß-tubulin are regulated by CCT8, and that increased CCT8 expression is associated with poor patient prognosis and cisplatin resistance in ESCC.

Using Next-Generation Sequencing to Explore Genetics and Race in the High School Classroom.

With the development of new sequencing and bioinformatics technologies, concepts relating to personal genomics play an increasingly important role in our society. To promote interest and understanding of sequencing and bioinformatics in the high school classroom, we developed and implemented a laboratory-based teaching module called "The Genetics of Race." This module uses the topic of race to engage students with sequencing and genetics. In the experimental portion of this module, students isolate their own mitochondrial DNA using standard biotechnology techniques and collect next-generation sequencing data to determine which of their classmates are most and least genetically similar to themselves. We evaluated the efficacy of this module by administering a pretest/posttest evaluation to measure student knowledge related to sequencing and bioinformatics, and we also conducted a survey at the conclusion of the module to assess student attitudes. Upon completion of our Genetics of Race module, students demonstrated significant learning gains, with lower-performing students obtaining the highest gains, and developed more positive attitudes toward scientific research.

The prognostic value of D-dimer levels in endometrial cancer patients treated with intensity-modulated radiation therapy.

Explain the important role of plasma D-dimer in cancers. Plasma D-dimer is increased in various tumors. However, the predictive value of plasma D-dimer is unclear. This study is aimed to evaluate the prognostic value of the D-dimer level in patients managed with intensity-modulated radiation for endometrial cancer. The D-dimer levels of forty patients with endometrial cancer were assessed before (D1) and after (D2) intensity-modulated radiation therapy (IMRT), respectively. The D-dimer level changes (ΔD) were defined as D2 minus D1. Cox regression and log-rank tests were used to evaluate the D-dimer levels in relation to progression free survival (PFS) and overall survival (OS). The OS and PFS of patients with a low D1 were significantly longer than those with a high D1 (P< 0.001, P< 0.001). We saw the similar correlation between D2, PFS and OS (P< 0.001, P< 0.001). Multivariate survival analyses showed that D-dimer was independently associated with OS and PFS in patients with endometrial cancer. The ΔD level was not related to the OS and PFS in endometrial cancer patients. The levels of D-dimer may be considered as an important predictor of PFS and OS in endometrial cancer patients treated with IMRT.

Integrative analysis of lung development-cancer expression associations reveals the roles of signatures with inverse expression patterns.

Recent studies have focused on exploring the associations between organ development and malignant tumors; however, the clinical relevance of the development signatures was inadequately addressed in lung cancer. In this study, we explored the associations between lung development and lung cancer progression by analyzing a total of two development and seven cancer datasets. We identified representative expression patterns (continuously up- and down-regulated) from development and cancer profiles, and inverse pattern associations were observed at both the gene and functional levels. Furthermore, we dissected the biological processes dominating the associations, and found that proliferation and immunity were respectively involved in the two inverse development-cancer expression patterns. Through sub-pathway analysis of the signatures with inverse expression patterns, we finally identified a 13-gene risk signature from the cell cycle sub-pathway, and evaluated its predictive performance for lung cancer patient clinical outcome using independent cohorts. Our findings indicated that the integrative analysis of development and cancer expression patterns provided a framework for identifying effective molecular signatures for clinical utility.

Histone deacetylase inhibitor suberoyl bis-hydroxamic acid suppresses cell proliferation and induces apoptosis in breast cancer cells.

Suberoyl bis­hydroxamic acid (SBHA) is a histone deacetylase inhibitor that has shown anticancer activity against numerous types of human cancer. The aim of the current study was to explore the effects of SBHA on the proliferation and apoptosis of breast cancer cells. MCF­7 breast cancer cells were treated with different concentrations of SBHA and tested for cell viability, apoptosis and gene expression changes. The results showed that SBHA significantly inhibited the proliferation of MCF­7 cells in a concentration­dependent manner, as determined using a Cell Counting kit­8 assay. SBHA­treated MCF­7 cells showed G0/G1 cell­cycle arrest, coupled with elevated expression levels of p21 and p27 proteins. Hoechst 33258 staining revealed cell shrinkage, chromosomal condensation and nuclear fragmentation in MCF­7 cells treated with SBHA. Flow cytometric analysis of Annexin V­stained cells showed that SBHA treatment induced apoptotic cell death in a concentration­dependent manner. Western blot analysis confirmed the upregulation of Bax and the downregulation of Bcl­2 by SBHA. In conclusion, these results indicate that SBHA exerts cytotoxic effects against human breast cancer cells, which involves the modulation of p21, p27 and Bcl­2 family proteins, consequently leading to cell­cycle arrest and apoptosis.

Identification of susceptibility variants in ADIPOR1 gene associated with type 2 diabetes, coronary artery disease and the comorbidity of type 2 diabetes and coronary artery disease.

OBJECTIVE: Adiponectin receptor 1 (encoded by ADIPOR1) is one of the major adiponectin receptors, and plays an important role in glucose and lipid metabolism. However, few studies have reported simultaneous associations between ADIPOR1 variants and type 2 diabetes (T2D), coronary artery disease (CAD) and T2D with CAD. Based on the "common soil" hypothesis, we investigated whether ADIPOR1 polymorphisms contributed to the etiology of T2D, CAD, or T2D with CAD in a Northern Han Chinese population. METHODS: Our multi-disease comparison study enrolled 657 subjects, including 165 with T2D, 173 with CAD, 174 with both T2D and CAD (T2D+CAD), and 145 local healthy controls. Six ADIPOR1 single nucleotide polymorphisms (SNPs) were genotyped and their association with disease risk was analyzed. RESULTS: Multi-case-control comparison identified two ADIPOR1 variants: rs3737884-G, which was simultaneously associated with an increased risk of T2D, CAD, and T2D+CAD (P-value range, 9.80×10(-5)-6.30×10(-4); odds ratio (OR) range: 1.96-2.42) and 16850797-C, which was separately associated with T2D and T2D+CAD (P-value range: 0.007-0.014; OR range: 1.71-1.77). The risk genotypes of both rs3737884 and 16850797 were consistently associated with common metabolic phenotypes in all three diseases (P-value range: 4.81×10(-42)-0.001). We observed an increase in the genetic dose-dependent cumulative risk with increasing risk allele numbers in T2D, CAD and T2D+CAD (P trend from 1.35×10(-5)-0.002). CONCLUSIONS: Our results suggest that ADIPOR1 risk polymorphisms are a strong candidate for the "common soil" hypothesis and could partially contribute to disease susceptibility to T2D, CAD, and T2D with CAD in the Northern Han Chinese population.

Suberoyl bis-hydroxamic acid enhances cytotoxicity induced by proteasome inhibitors in breast cancer cells.

BACKGROUND: Suberoyl bis-hydroxamic acid (SBHA) is a histone deacetylase (HDAC) inhibitor and exerts anti-growth effects in several malignancies including breast cancer. Proteasome inhibitors such as Bortezomib and MG-132 constitute novel anticancer agents. In this study, we investigated the synergistic antitumour activity of SBHA in combination with proteasome inhibitors. METHODS: MCF-7 and MDA-MB-231 breast cancer cells were treated with SBHA, Bortezomib, and MG-132 alone or in combination for 72 h. Cell proliferation, colony formation, apoptosis and gene expression changes were examined. RESULTS: SBHA, Bortezomib, and MG-132 alone significantly inhibited the proliferation and colony formation and induced apoptosis in MCF-7 and MDA-MB-231 cells. Combined treatment showed a good synergistic antitumour effect against breast cancer cells. The p53 protein level was significantly elevated by combined treatment with SBHA and proteasome inhibitors. Moreover, combined treatment increased the expression of Bax, Bcl-xS, and Bak and decreased the expression of Bcl-2. Combination of SBHA with proteasome inhibitors causes synergistic anticancer effects on breast cancer cells. The potential molecular mechanism may involve induction of p53 and modulation of the Bcl-2 family proteins. CONCLUSION: These findings warrant further investigation of the therapeutic benefits of combination of SBHA with proteasome inhibitors in breast cancer.

Nrf2 is associated with the regulation of basal transcription activity of the BRCA1 gene.

BRCA1 is closely related to the pathogenesis of breast cancer. The activity of BRCA1 promoter is regulated by transcriptional factors. The transcription factor Nrf2 (Nuclear factor-erythroid-2p45-related factor 2) is a potent transcriptional activator and plays a central role in inducible expression of many cytoprotective genes. In this report, we found that over-expression of Nrf2 stimulated BRCA1 expression, knockdown of Nrf2 attenuated BRCA1 expression. Nrf2 also interacted with CBP and p300 to form an active transcription complex, which could bind to the ARE (antioxidant response element) site on the BRCA1 promoter and activate its transcription by inducing histone acetylation. Our finding could lead to a better understanding of the development of breast cancer.

Biweekly docetaxel-containing chemotherapy may be the optimal schedule.

The dosing schedule of docetaxel may affect its clinical activity and toxicity profile. Although triweekly docetaxel has higher antitumor activity but more severe hematological toxicity, weekly docetaxel seems to have less activity or fewer adverse events. To evaluate the efficacy and toxicity of biweekly docetaxel and mitoxantrone in patients with advanced breast cancer, the regimen consisting of docetaxel (60 mg/m), and mitoxantrone (8 mg/m) was administered intravenously to 59 patients every 2 weeks. Most (54.2%) of the patients experienced objective responses. The median time to progression for the whole group was 6.8 months. The median time to progression for patients with complete or partial response was 10.3 months, but only 3.6 months for patients with stable or progressive disease (P<0.001). Grade III/IV adverse events of neutropenia, thrombocytopenia, anemia, febrile neutropenia, and nausea/vomiting were documented in 61.0, 6.8, 3.4, 3.4, and 3.4% of the patients, respectively. The median overall survival was 16.9 months. In conclusion, biweekly use of docetaxel and mitoxantrone is a highly effective and well-tolerated regimen for patients with advanced breast cancer. The optimal dosage of docetaxel in combination with chemotherapeutic regimen may be given every 2 weeks.

[Cytogenetic and interphase FISH studies in the diagnosis of malignant lymphomas].

OBJECTIVE: To evaluate the role of cytogenetic study and interphase FISH analysis in differential diagnosis of patients with clinical and/or cytological diagnosis as lymphoma or "suspicious for lymphoma". METHODS: Routine histology, immunohistochemistry, cytogenetics and interphase FISH studies were used to assess 223 cases with superficial lymph nodes of not less than 1. 5 cm in diameter. The probe used in the interphase FISH assays is the Vysis' LSI IGH Dual Color, Break Apart Rearrangement Probe. RESULTS: Based on these studies, forty-four patients were diagnosed as Hodgkin's lymphomas ( HL) , 162 as Non-Hodgkin's lymphomas ( NHL) , 11 with benign diseases and 4 as other malignancies, while the remaining 2 cases were discarded due to tissue necrosis. Using interphase FISH, abnormalities of immunoglobulin heavy chain gene (IGH) were detected in 6/44 (13.6%) and 83/162 (51.2%) in the HIL and NHL cases, respectively, while none was observed in 11 cases with a benign disease (P <0. 001). Combining cytogenetics and FISH studies, the detection rates for HL and NHL cases then increased to 15.9% and 77. 8%, respectively, otherwise, 3 of whom could not have made definite diagnosis. CONCLUSION: Interphase FISH assay is a rapid and sensitive tool for detecting IGH abnormalities. Both cytogenetics and interphase FISH analyses may play a significant role in diagnosis of lymphomas.