Nanoparticles targeting OPN loaded with BY1 inhibits vascular restenosis by inducing FTH1-dependent ferroptosis in vascular smooth muscle cells.

Vascular restenosis following angioplasty continues to pose a significant challenge. The heterocyclic trioxirane compound [1, 3, 5-tris((oxiran-2-yl)methyl)-1, 3, 5-triazinane-2, 4, 6-trione (TGIC)], known for its anticancer activity, was utilized as the parent ring to conjugate with a non-steroidal anti-inflammatory drug, resulting in the creation of the spliced conjugated compound BY1. We found that BY1 induced ferroptosis in VSMCs as well as in neointima hyperplasia. Furthermore, ferroptosis inducers amplified BY1-induced cell death, while inhibitors mitigated it, indicating the contribution of ferroptosis to BY1-induced cell death. Additionally, we established that ferritin heavy chain1 (FTH1) played a pivotal role in BY1-induced ferroptosis, as evidenced by the fact that FTH1 overexpression abrogated BY1-induced ferroptosis, while FTH1 knockdown exacerbated it. Further study found that BY1 induced ferroptosis by enhancing the NCOA4-FTH1 interaction and increasing the amount of intracellular ferrous. We compared the effectiveness of various administration routes for BY1, including BY1-coated balloons, hydrogel-based BY1 delivery, and nanoparticles targeting OPN loaded with BY1 (TOP@MPDA@BY1) for targeting proliferated VSMCs, for prevention and treatment of the restenosis. Our results indicated that TOP@MPDA@BY1 was the most effective among the three administration routes, positioning BY1 as a highly promising candidate for the development of drug-eluting stents or treatments for restenosis.

Ganonorsterone A, a norsteroid from the medicinal fungus Ganoderma lingzhi.

Phytochemical investigation on the fruiting bodies of the medicinal fungus Ganoderma lingzhi led to the isolation of a new norsteroid, namely ganonorsterone A (1), together with one known steroid, cyathisterol (2). The structure and absolute configuration of compound 1 were assigned by extensive analysis of MS, NMR data, and quantum-chemical calculations including electronic circular dichroism (ECD) and calculated 13C NMR-DP4+ analysis. Bioassay results showed that compound 1 displayed moderate inhibition on NO production in RAW 264.7 macrophages.

Ubiquitin-specific proteases: From biological functions to potential therapeutic applications in gastric cancer.

Deubiquitination, a post-translational modification regulated by deubiquitinases, is essential for cancer initiation and progression. Ubiquitin-specific proteases (USPs) are essential elements of the deubiquitinase family, and are overexpressed in gastric cancer (GC). Through the regulation of several signaling pathways, such as Wnt/ß-Catenin and nuclear factor-κB signaling, and the promotion of the expression of deubiquitination- and stabilization-associated proteins, USPs promote the proliferation, metastasis, invasion, and epithelial-mesenchymal transition of GC. In addition, the expression of USPs is closely related to clinicopathological features, patient prognosis, and chemotherapy resistance. USPs therefore could be used as prognostic biomarkers. USP targeting small molecule inhibitors have demonstrated strong anticancer activity. However, they have not yet been tested in the clinic. This article provides an overview of the latest fundamental research on USPs in GC, aiming to enhance the understanding of how USPs contribute to GC progression, and identifying possible targets for GC treatment to improve patient survival.

Characteristics of tunable aluminum-doped Ga2O3thin films and photodetectors.

Aluminum-doped Ga2O3(AGO) thin films were prepared by plasma-enhanced atomic layer deposition (PE-ALD). The growth mechanism, surface morphology, chemical composition, and optical properties of AGO films were systematically investigated. The bandgap of AGO films can be theoretically set between 4.65 and 6.8 eV. Based on typical AGO films, metal-semiconductor-metal photodetectors (PDs) were created, and their photoelectric response was examined. The preliminary results show that PE-ALD grown AGO films have high quality and tunable bandgap, and AGO PDs possess superior characterizations to undoped films. The AGO realized using PE-ALD is expected to be an important route for the development of a new generation of gallium oxide-based photodetectors into the deep-ultraviolet.

Radiomics model based on multi-sequence MRI for preoperative prediction of ki-67 expression levels in early endometrial cancer.

To validate a radiomics model based on multi-sequence magnetic resonance imaging (MRI) in predicting the ki-67 expression levels in early-stage endometrial cancer, 131 patients with early endometrial cancer who had undergone pathological examination and preoperative MRI scan were retrospectively enrolled and divided into two groups based on the ki-67 expression levels. The radiomics features were extracted from the T2 weighted imaging (T2WI), dynamic contrast enhanced T1 weighted imaging (DCE-T1WI), and apparent diffusion coefficient (ADC) map and screened using the Pearson correlation coefficients (PCC). A multi-layer perceptual machine and fivefold cross-validation were used to construct the radiomics model. The receiver operating characteristic (ROC) curves analysis, calibration curves, and decision curve analysis (DCA) were used to assess the models. The combined multi-sequence radiomics model of T2WI, DCE-T1WI, and ADC map showed better discriminatory powers than those using only one sequence. The combined radiomics models with multi-sequence fusions achieved the highest area under the ROC curve (AUC). The AUC value of the validation set was 0.852, with an accuracy of 0.827, sensitivity of 0.844, specificity of 0.773, and precision of 0.799. In conclusion, the combined multi-sequence MRI based radiomics model enables preoperative noninvasive prediction of the ki-67 expression levels in early endometrial cancer. This provides an objective imaging basis for clinical diagnosis and treatment.

Value of Multimodal Diffusion-weighted Imaging in Preoperative Evaluation of Ki-67 Expression in Endometrial Carcinoma.

PURPOSE: To investigate the value of multimodal diffusion weighted imaging (DWI) in preoperative evaluation of Ki-67 expression of endometrial carcinoma (EC). MATERIALS AND METHODS: Patients who had undergone pelvic DWI, intravoxel incoherent motion (IVIM), and diffusion kurtosis imaging (DKI) sequence MRI scan before surgery were retrospectively enrolled. Single index model, double index model, and DKI were used for post-processing of the DWI data, and the apparent diffusion coefficient (ADC), real diffusion coefficient (D), pseudo diffusion coefficient (D*), perfusion fraction (f), non-Gaussian mean diffusion kurtosis (MK), mean diffusion coefficient (MD) and anisotropy fraction (FA) were calculated and compared between the Ki-67 high (≥50%) and low (<50%) expression groups. RESULTS: Forty-two patients with a median age of 56 (range 37 - 75) years were enrolled, including 15 patients with a high Ki-67 (≥50%) expression and 27 with a low Ki-67 (<50%) expression. The MK (0.91 ± 0.12 vs. 0.76 ± 0.12) was significantly (P<0.05) higher while MD (0.99 ± 0.17 vs. 1.16 ± 0.22), D (0.55 ± 0.06 vs. 0.62 ± 0.08), and f (0.21 vs. 0.28) were significantly (P<0.05) lower in the high than in the low expression group. The combined model of MK, MD, D, and f-values had the largest area under the curve (AUC) value of 0.869 (95% CI: 0.764-0.974), sensitivity 0.733 and specificity 0.852, followed by the MK value with an AUC value 0.827 (95% CI: 0.700-0.954), sensitivity 0.733 and specificity 0.815. CONCLUSIONS: IVIM and DKI have certain diagnostic values for preoperative evaluation of the EC Ki-67 expression, and the combined model has the highest diagnostic efficiency.

Late-onset cblC defect: clinical, biochemical and molecular analysis.

BACKGROUND: cblC defect is the most common type of methylmalonic acidemia in China. Patients with late-onset form (>1 year) are often misdiagnosed due to heterogeneous symptoms. This study aimed to describe clinical characteristics and evaluate long-term outcomes of Chinese patients with late-onset cblC defect. METHODS: A total of 85 patients with late-onset cblC defect were enrolled. Clinical data, including manifestations, metabolites, molecular diagnosis, treatment and outcome, were summarized and analyzed. RESULTS: The age of onset ranged from 2 to 32.8 years old (median age 8.6 years, mean age 9.4 years). The time between first symptoms and diagnosis ranged from a few days to 20 years (median time 2 months, mean time 20.7 months). Neuropsychiatric symptoms were presented as first symptoms in 68.2% of cases, which were observed frequently in schoolchildren or adolescents. Renal involvement and cardiovascular disease were observed in 20% and 8.2% of cases, respectively, which occurred with the highest prevalence in preschool children. Besides the initial symptoms, the disease progressed in most patients and cognitive decline became the most frequent symptom overall. The levels of propionylcarnitine, propionylcarnitine / acetylcarnitine ratio, methylmalonic acid, methylcitric acid and homocysteine, were decreased remarkably after treatment (P<0.001). Twenty-four different mutations of MMACHC were identified in 78 patients, two of which were novel. The c.482G>A variant was the most frequent mutated allele in this cohort (25%). Except for 16 patients who recovered completely, the remaining patients were still left with varying degrees of sequelae in a long-term follow-up. The available data from 76 cases were analyzed by univariate analysis and multivariate logistic regression analysis, and the results showed that the time from onset to diagnosis (OR = 1.025, P = 0. 024) was independent risk factors for poor outcomes. CONCLUSIONS: The diagnosis of late-onset cblC defect is often delayed due to poor awareness of its various and nonspecific symptoms, thus having an adverse effect on the prognosis. It should be considered in patients with unexplained neuropsychiatric and other conditions such as renal involvement, cardiovascular diseases or even multiple organ damage. The c.482G>A variant shows the highest frequency in these patients. Prompt treatment appears to be beneficial.

Role of N6-methyladenosine RNA modification in gastric cancer.

N6-methyladenosine (m6A) RNA methylation is the most prevalent internal modification of mammalian messenger RNA. The m6A modification affects multiple aspects of RNA metabolism, including processing, splicing, export, stability, and translation through the reversible regulation of methyltransferases (Writers), demethylases (Erasers), and recognition binding proteins (Readers). Accumulating evidence indicates that altered m6A levels are associated with a variety of human cancers. Recently, dysregulation of m6A methylation was shown to be involved in the occurrence and development of gastric cancer (GC) through various pathways. Thus, elucidating the relationship between m6A and the pathogenesis of GC has important clinical implications for the diagnosis, treatment, and prognosis of GC patients. In this review, we evaluate the potential role and clinical significance of m6A-related proteins which function in GC in an m6A-dependent manner. We discuss current issues regarding m6A-targeted inhibition of GC, explore new methods for GC diagnosis and prognosis, consider new targets for GC treatment, and provide a reasonable outlook for the future of GC research.

Exposure to Commonly Used Drugs and the Risk of Gastric Cancer: An Umbrella Review of Meta-Analyses.

Recently, attention has been paid to some medications and gastric cancer (GC) risk. This review aimed to evaluate associations between commonly used drugs and GC risk and to grade evidence from published systematic reviews and meta-analyses. This umbrella review was registered in PROSPERO (CRD42022320276). The systematic reviews and meta-analyses of observational studies were retrieved by searching Embase, PubMed, and Web of Science. The evidence strength of commonly used drugs and GC risk was categorized into four grades: weak, suggestive, highly suggestive, and strong. Of 19 associations between commonly used drugs and GC risk and its subtypes, none was supported by convincing or highly suggestive evidence. The risk of GC related to non-steroidal anti-inflammatory drugs (NSAIDs), non-aspirin NSAIDs, and acid-suppressive drugs, as well as the risk of non-cardia GC related to NSAIDs and aspirin, was supported by suggestive evidence. The results showed that a reduced GC risk was associated with two drug types (NSAIDs and non-aspirin NSAIDs), and an increased GC risk was associated with acid-suppressing drugs at the suggestive evidence level. Moreover, NSAIDs and aspirin reduced non-cardia GC risk as supported by suggestive evidence. However, the evidence supporting statins or metformin in reducing GC risk was weak, and thus future studies are required to clarify these associations.

Metacognitions associated with reproductive concerns: A cross-sectional study of young adult female cancer survivors in China.

Objective: Cancer and its treatments affect patients' fertility potential. This study examined the prevalence of reproductive concerns and their relationship with metacognitions among Chinese young adult female cancer survivors (YAFCS). Methods: A total of 318 YAFCS (aged 18-39) completed an online survey from March to December 2021. Participants reported sociodemographic characteristics, reproductive concerns and metacognitions. Reproductive concerns were measured using the Reproductive Concerns after Cancer scale (RCAC), and metacognitions were measured by the Short Form of Metacognitions Questionnaire (MCQ-30). We used Pearson correlation analysis to examine associations between metacognitions and reproductive concerns across multiple domains and multivariable linear regression to determine the influencing factors of reproductive concerns. Results: The mean score of reproductive concern among YAFCS was 49.97 ± 12.52. A total of 57.9% of participants reported a high level of concern regarding at least one dimension of reproductive concerns, and they were most concerned about their child's health and least concerned about partner disclosure of fertility status. We also found a moderate association between RCAC and MCQ-30 scores (r = 0.408, p < 0.001). In multivariate analyses, metacognitions, especially negative metacognitive beliefs had an impact on reproductive concerns among YAFCS (p < 0.001). Conclusion: Higher reproductive concerns were associated with higher metacognitions among YAFCS, especially with negative metacognitive beliefs. Oncology professionals should pay attention to assessing reproductive concerns in patients who want to have children or who have no children. Moreover, metacognitive beliefs may be an intervention target for alleviating reproductive concerns among YAFCS.

MethHC 2.0: information repository of DNA methylation and gene expression in human cancer.

DNA methylation is an important epigenetic regulator in gene expression and has several roles in cancer and disease progression. MethHC version 2.0 (MethHC 2.0) is an integrated and web-based resource focusing on the aberrant methylomes of human diseases, specifically cancer. This paper presents an updated implementation of MethHC 2.0 by incorporating additional DNA methylomes and transcriptomes from several public repositories, including 33 human cancers, over 50 118 microarray and RNA sequencing data from TCGA and GEO, and accumulating up to 3586 manually curated data from >7000 collected published literature with experimental evidence. MethHC 2.0 has also been equipped with enhanced data annotation functionality and a user-friendly web interface for data presentation, search, and visualization. Provided features include clinical-pathological data, mutation and copy number variation, multiplicity of information (gene regions, enhancer regions, and CGI regions), and circulating tumor DNA methylation profiles, available for research such as biomarker panel design, cancer comparison, diagnosis, prognosis, therapy study and identifying potential epigenetic biomarkers. MethHC 2.0 is now available at http://awi.cuhk.edu.cn/∼MethHC.

Comparison of the performance of two depression rating scales in patients with epilepsy in southern China.

OBJECTIVE: The aim of this study was to evaluate and compare the performance of the Chinese version of the Neurological Disorder Depression Inventory for Epilepsy (CNDDI-E) with that of the depression subscale of the Hospital Anxiety and Depression Scale (C-HADS-D) as screening tools for depression in the same patients with epilepsy (PWE). METHODS: A total of 213 consecutive PWE were evaluated. Receiver operating characteristic (ROC) analysis was performed using the C-NDDI-E and C-HADS-D as predictors and the Chinese version of the Mini International Neuropsychiatric Interview (C-MINI) as the gold standard. RESULTS: The area under the curve (AUC) for the C-NDDI-E was 0.870, and the optimal cutoff score was >11 (sensitivity 85.71%, specificity 79.78%); for the C-HADS-D, the AUC was 0.804, and the optimal cutoff score was >5 (sensitivity 85.71%, specificity 62.36%). The AUC for the C-NDDI-E was larger than the AUC for the C-HADS-D, but the comparison of the AUCs revealed no significant differences (P = 0.1444). CONCLUSION: Our findings indicate that the C-NDDI-E and C-HADS-D have high validity and support the use of these screening tools for depression in PWE. Moreover, the C-NDDI-E is a better screening scale for diagnosing depression than the C-HADS-D according to the results of this study.

MYCT1 Inhibits the Adhesion and Migration of Laryngeal Cancer Cells Potentially Through Repressing Collagen VI.

MYCT1, a target of c-Myc, inhibits laryngeal cancer cell migration, but the underlying mechanism remains unclear. In the study, we detected differentially expressed genes (DEGs) from laryngeal cancer cells transfected by MYCT1 using RNA-seq (GSE123275). DEGs from head and neck squamous cell carcinoma (HNSCC) were first screened by comparison of transcription data from the Gene Expression Omnibus (GSE6631) and the Cancer Genome Atlas (TCGA) datasets using weighted gene co-expression network analysis (WGCNA). GO and KEGG pathway analysis explained the functions of the DEGs. The DEGs overlapped between GSE6631and TCGA datasets were then compared with ours to find the key DEGs downstream of MYCT1 related to the adhesion and migration of laryngeal cancer cells. qRT-PCR and Western blot were applied to validate gene expression at mRNA and protein levels, respectively. Finally, the cell adhesion, migration, and wound healing assays were to check cell adhesion and migration abilities, respectively. As results, 39 overlapping genes were enriched in the GSE6631 and TCGA datasets, and most of them revealed adhesion function. Thirteen of 39 genes including COL6 members COL6A1, COL6A2, and COL6A3 were overlapped in GSE6631, TCGA, and GSE123275 datasets. Similar to our RNA-seq results, we confirmed that COL6 is a target of MYCT1 in laryngeal cancer cells. We also found that MYCT1 inhibited the adhesion and migration of laryngeal cancer cells via COL6. These indicate that COL6 is a potential target of MYCT1 and participates the adhesion and migration of laryngeal cancer cells, which provides an important clue for further study on how MYCT1 regulating COL6 in laryngeal cancer progression.

Synchronous of gastric adenocarcinoma and schwannoma: report of a case and review of literatures.

We presented a case of 80-year-old male with long term stomachache, marasmus and anaemia. Endoscopic evaluation suggested the malignant ulcerative tumor on the Gastric antrum, and biopsy confirmed the diagnosis of gastric adenocarcinoma. Surprisingly, in resected specimen the pathologist found a nodule just below the ulcer with clear boundary and gray-yellow section. Histologically, the whole lesion was composed with adenocarcinoma area and spindle tumor cells area. In the spindle tumor cells area, the cells with round or oval nuclei, eosinophilic cytoplasm, and these cells showed bundle or fence-like arrangement. Immunohistochemistry study presented positive expression of vimentin, S-100 and GFAP, negative expression of SMA, desmin, CD34, CD117 and Dog-1, which suggested the diagnosis of co-occurrence of gastric adenocarcinoma and schwannoma. To our knowledge, it is an extremely rare case that only two cases have been reported.

Mesothelioma of the tunica vaginalis testis with prominent adenomatoid features: a case report.

Malignant mesotheliomas of the testis arise from the tunica vaginalis, formed from the evagination of the abdominal peritoneum into the scrotum. It is an extremely rare tumor representing 0.3% to 5% of all malignant mesotheliomas. We presented an interesting case of 68-year-old male with swelling and slightly painful in the right scrotum. Histologically, the lesion were composed of small tubular, microcystic, gland lined by flattened epithelioid cells and vague signet ring cells set in a myxofibrous stroma, which is resemblance to adenomatoid tumor. But the tumor cells showed significant atypical cytologic morphology and invaded into spermatic cord tissue, which indicated the diagnosis of malignant tumor. Immunohistochemistry study showed positive expression of CK, CK5/6, CK7, Calretinin, D2-40 and Vimentin which indicated the diagnosis of malignant mesothelioma. This case of mesothelioma should be classified as epithelial in type. To our knowledge, the mesothelioma of the tunica vaginalis testis with adenomatoid tumor-like microscopic features is very rare.

Mental health is the most important factor influencing quality of life in elderly left behind when families migrate out of rural China / A saúde mental é o fator mais importante que influencia a qualidade de vida de idosos deixados para trás quando as famílias emigram da China rural / La salud mental es el factor más importante que influye en la calidad de vida en los adultos mayores que se quedan cuando las familias emigran fuera de las zonas rurales de China

OBJECTIVES: to investigate the quality of life and the associated factors on left behind elderly in rural China. METHOD: the research was conducted cluster sampling to select 456 elderly left behind when family members migrated out of rural China to participate in a cross-sectional study by completing a general data questionnaire and Quality of Life questionnaire. RESULTS: 91.5% of the elderly requested psychological counseling and education. For the elderly, scores for mental health (39.56±13.73) were significantly lower compared with Chinese standard data (61.6±13.7) (P<0.001). Age, chronic disease type, gender, residence pattern and economic support from children were the main psychological factors influencing this population. CONCLUSION: mental health is the most important factor influencing quality of life of elderly left behind when family members migrated out of rural China. Our study suggested a need to widely establish a general practitioner team for psychological intervention for improving rural elderly people's Quality of Life level, especially in the psychological domain. .

OBJETIVOS: investigar a qualidade de vida e fatores associados de idosos deixados para trás na China rural. MÉTODO: foi realizada amostragem por conglomerado para selecionar 456 idosos deixados para trás quando os membros da família emigram da China rural. Este é um estudo transversal com preenchimento de um questionário de dados gerais e de qualidade de vida. RESULTADOS: 91,5% dos idosos convidados solicitaram aconselhamento e educação psicológicos. Para os idosos, os escores de saúde mental (39,56±13,73) foram significativamente menores em comparação aos dados padrões chineses (61,6±13,7) (p<0,001). A idade, tipo de doença crônica, gênero, tipo de moradia e suporte econômico dos filhos foram os principais fatores psicológicos que influenciaram essa população. CONCLUSÃO: a saúde mental é o fator mais importante que influencia a qualidade de vida de idosos deixados para trás quando os familiares emigraram da China rural. Este estudo sugere a necessidade de criação de ampla equipe de generalistas para intervenção psicológica, com o intuito de melhorar o nível de qualidade de vida de idosos de áreas rurais, especialmente no domínio psicológico. .

OBJETIVOS: investigar la calidad de vida y los factores asociados a los adultos mayores que se quedan en las zonas rurales de China. MÉTODO: la investigación se realizó por medio de muestreo por conglomerados para seleccionar 456 adultos mayores que se quedaron cuando los miembros de la familia emigraron de zonas rurales de China, para participar en un estudio de corte transversal, completando un cuestionario de datos generales y cuestionario de calidad de vida. RESULTADOS: el 91.5% de los adultos mayores solicitó asistencia psicológica y educación. Para los adultos mayores, las puntuaciones de salud mental (39.56±13.73) fueron significativamente más bajos en comparación con los datos estándar de China (61.6±13.7) (p<0.001). La edad, el tipo de enfermedad crónica, el género, el patrón de residencia y el apoyo económico de los hijos fueron los principales factores psicológicos que influencian esta población. CONCLUSIÓN: la salud mental es el factor más importante que influye la calidad de vida de los adultos mayores que se quedan cuando los miembros de la familia emigran de las zonas rurales de China. Nuestro estudio sugiere la necesidad de establecer ampliamente un equipo médico general para la intervención psicológica para mejorar el nivel de la Calidad de Vida de la población rural de edad avanzada, sobre todo en el dominio psicológico. .

Occult tumor metastasis and the prognostic value of sentinel lymph nodes in rectal cancer.

The aim of the present study to evaluate the application of sentinel lymph node (SLN) pathology in rectal cancer using ex vivo mapping and to investigate the incidence and prognostic value of occult SLN metastasis in routine node-negative specimens. Specimens (n=117) of rectal cancer were examined using a combination of routine pathology and ex vivo SLN mapping. The inspected SLNs were further treated with immunohistochemical staining for occult cancer foci. The log-rank test was used to assess survival. SLNs were examined in 112 of the included specimens with a total number of 212, resulting in an identification rate of 95.7% (112/117). The status of SLNs accurately reflected N stage in 93.8% (105/112) of cases and the sensitivity was 75.6% (31/41) in detecting nodal metastasis. The accuracy of SLN pathology decreased in cancers of more advanced TNM stages (P=0.001). In 74 cases with routine node-negative (N0) disease, SLN micrometastasis (MIC) and isolated tumor cells (ITC) were examined in 9 and 4 cases, while the remaining 61 were regarded as negative (NEG). The log-rank test revealed poorer disease-free and overall survival of the MIC group compared with the NEG group. However, the findings from the ITC group were not significant compared with those from the MIC and NEG groups. In conclusion, ex vivo SLN pathology is practical and accurate in rectal cancer; however, its utility is limited in cases of advanced disease. Immunohistochemically detected SLN micrometastasis in node-negative cases is therefore a predictor of poorer outcome, and may therefore be listed as a marker for adjuvant therapy.

Mesorectal and lateral node metastasis and micrometastasis in lower rectal cancer.

BACKGROUND/AIMS: To study lymph node metastasis and micrometastasis within the mesorectum and lateral pelvic area in lower rectal cancer. METHODOLOGY: Specimens of 96 patients, who underwent total mesorectal excision (TME) and lateral lymph node dissection (LLND), were included. RESULTS: An average of 19.4 mesorectal lymph nodes were examined. Horizontally, more than 30 percent of involved lymph nodes were located in the outer layer of the mesorectum. Longitudinally, metastasized lymph nodes were harvested from the distal, paratumoral and proximal mesorectum of 6, 42 and 29 specimens, respectively. Fourteen specimens were observed to have circumferential resection margin involvement, while another 3 had micrometastasis. The average amount of harvested lateral pelvic lymph nodes was 12.1. Most (1052/1159) of the lateral nodes were defined as negative. Fourteen and 11 specimens were examined to contain lateral node metastasis and micrometastasis, respectively. Among regions of the lateral pelvic area, middle rectal root (44%), internal iliac (28%) and obturator (20%) were more likely to be involved by cancer spread. CONCLUSIONS: Complete excision of the mesorectum is essential for local clearance of lower rectal cancer. Mesorectal margin involvement and lateral metastasis underlined the limitation of single surgical procedure, thus suggesting the significance of neoadjuvant therapy.

Establishment and biological characteristics of human multiple myeloma cell line CZ-1.

BACKGROUND: There were only 3 multiple myeloma (MM) cell lines established in China. In this study, we succeeded in establishing a novel MM cell line and analyzed its biological characteristics. METHODS: Mononuclear cells isolated from the peripheral blood (PB) and bone marrow (BM) of a patient with advanced MM (lambda light chain type) were cultured in medium. Cell morphology was analyzed by Wright-Giemsa-staining and cytochemical staining, immunophenotyping by flow cytometry and cytogenetic analysis by chromosome RHG-banding technique. Quantitative fluorescent polymerase chain reaction (PCR) was used to detect Epstein - Barr virus (EBV) DNA. RESULTS: The established cell line could survive and proliferate in the presence of feeder cells or conditioned medium. The cells secreted lambda light chain and were negative for EBV. The Wright-Giemsa-staining showed typical plasmablast or plasma cell morphology. The cytochemical staining of the cells showed the following reactivity patterns: positive for acid phosphatase, negative for myeloperoxidase. The immunoprofile of the cells was concordant with that of MM cells: positive for CD10, CD28, CD38, CD138, CD56, CD49d, CD44, CD54 and CD58, negative for CD19, CD40, CD95, CD95L, CD34, CD2 and CD5. The cytogenetic analysis showed complex chromosome abnormality of i (1q+), 8q+, 13q+, i (17q), i (18q) and +M. There was no difference in morphology, immunophenotype and cytogenetics between cells from PB and BM. CONCLUSIONS: An MM cell line secreting lambda light chain named CZ-1 was established. The cells from both PB and BM have the same biological characteristics.

[Detection of IgH-MMSET fusion gene in multiple myeloma patients and its significance].

OBJECTIVE: To detect the IgH-MMSET fusion gene resulted from t (4;14) translocation in multiple myeloma and illuminate its significance. METHODS: IgH-MMSET fusion gene was detected in bone marrow specimens of 25 multiple myeloma (MM) patients and MM cell line NCI-H929 using reverse-transcription PCR (RT-PCR) assay followed by nested PCR to increase the sensitivity. The purified PCR products were cloned into pGEM-T vector and then sequenced using M13 forward primers. The fragment sequences were compared with that in GenBank to find matched sequences. RESULTS: Only a 438 base pair long fragment was obtained after RT-PCR assay and was confirmed by sequencing to be a fusion gene product of IgH gene and MMSET gene in MM cell line NCI-H929. The breakpoints were located within the C micro region of IgH gene on chromosome 14 and intron 3 of MMSET gene on chromosome 4. IgH-MMSET hybrid transcripts were detected in 3 of 25 MM patients through nested PCR assay. The amplified fragments of the 3 patients were 237 base pairs (bp), 239 bp and 239 bp in length, respectively. The breakpoints on chromosome 4 were identical to that of NCI-H929 cell. CONCLUSIONS: The formation of IgH-MMSET fusion gene is resulted from t (4;14) translocation in MM. The incidence rate is 12.0%. The presence of IgH-MMSET fusion gene may predict poor prognosis.