Transformation of marginal zone lymphoma into high-grade B-cell lymphoma expressing terminal deoxynucleotidyl transferase: A case report.

BACKGROUND: High-grade B-cell lymphoma (HGBL) is an unusual malignancy that includes myelocytomatosis viral oncogene (MYC), B-cell lymphoma-2 (BCL-2), and/or BCL-6 rearrangements, termed double-hit or triple-hit lymphomas, and HGBL-not otherwise specific (HGBL-NOS), which are morphologically characteristic of HGBL but lack MYC, BCL-2, or BCL-6 rearrangements. HGBL is partially transformed by follicular lymphoma and other indolent lymphoma, with few cases of marginal zone lymphoma (MZL) transformation. HGBL often has a poor prognosis and intensive therapy is currently mainly advocated, but there is no good treatment for these patients who cannot tolerate chemotherapy. CASE SUMMARY: We reported a case of MZL transformed into HGBL-NOS with TP53 mutation and terminal deoxynucleotidyl transferase expression. Gene analysis revealed the gene expression profile was identical in the pre- and post-transformed tissues, suggesting that the two diseases are homologous, not secondary tumors. The chemotherapy was ineffective and the side effect was severe, so we tried combination therapy including venetoclax and obinutuzumab. The patient tolerated treatment well, and reached partial response. The patient had recurrence of hepatocellular carcinoma and died of multifunctional organ failure. He survived for 12 months after diagnosis. CONCLUSION: Venetoclax combined with obinutuzumab might improve the survival in some HGBL patients, who are unsuitable for chemotherapy.

XRCC5/6 polymorphisms and their interactions with smoking, alcohol consumption, and sleep satisfaction in breast cancer risk: A Chinese multi-center study.

BACKGROUND: X-ray repair cross-complementary 5 (XRCC5) and 6 (XRCC6) are critical for DNA repair. Few studies have assessed their association with breast cancer risk, and related gene-environment interactions remain poorly understood. This study aimed to determine the influence of XRCC5/6 polymorphisms on breast cancer risk, and their interactions with cigarette smoking, alcohol consumption, and sleep satisfaction. METHODS: The study included 1039 patients with breast cancer and 1040 controls. Four single-nucleotide polymorphisms of XRCC5 and two of XRCC6 were genotyped. Information about smoking, alcohol consumption, and sleep satisfaction was collected through questionnaires. Odds ratios (OR) and related 95% confidence intervals (95% CI) were assessed using unconditional logistic regression models. Gene-environment interactions were analyzed using logistic regression with multiplicative interaction models. RESULTS: XRCC5 rs16855458 was associated with increased breast cancer risk in the co-dominant (ptrend  = 0.003) and dominant (CA + AA vs. CC, OR = 1.29, 95% CI = 1.07-1.56, p = 0.008) genetic models after Bonferroni correction. The CG + GG genotype of XRCC6 rs2267437 was associated with an increased risk of estrogen receptor-negative/progesterone receptor-negative (ER-/PR-) breast cancer (CG + GG vs. CC: OR = 1.54, 95% CI = 1.12-2.13, p = 0.008) after Bonferroni correction. Moreover, an antagonistic interaction between XRCC5 rs16855458 and alcohol consumption (pinteraction  = 0.017), and a synergistic interaction between XRCC6 rs2267437 and sleep satisfaction were associated with breast cancer risk (pinteraction  = 0.0497). However, these interactions became insignificant after Bonferroni correction. CONCLUSION: XRCC5 rs16855458 was associated with breast cancer risk, and XRCC6 rs2267437 was associated with the risk of ER-/PR- breast cancer. Breast cancer risk associated with XRCC5 and XRCC6 polymorphisms might vary according to alcohol consumption and sleep satisfaction, respectively, and merit further investigation.

Relationship Between Lifestyle Habits and Health-Related Quality of Life of Recently Diagnosed Breast Cancer Patients: A Comparison Between Younger and Older Women in China.

Objective: The aim of this study was to evaluate the relationship between lifestyle habits and health-related quality of life (HRQoL) among different ages who were initially diagnosed with breast cancer (within the first 2 weeks) and to determine the contribution of lifestyle habits factors on HRQoL. Methods: Patients with breast cancer were recruited from 22 hospitals in 11 provinces or municipalities in northern and eastern China. The Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) was used to measure HRQoL. Chi-square test, ANOVA, and multivariable generalized linear models were conducted to identify the differences in HRQoL between two age groups (age <50 years and ≥50 years) and to evaluate the contribution of lifestyle habits factors on HRQoL of patients with breast cancer. Results: About 1,199 eligible patients with breast cancer were used for analysis. Younger women (aged <50 years) appeared to show lower scores than older women (aged ≥50 years) in HRQoL subscales, including emotional well-being (p = 0.003), functional well-being (p = 0.006), breast cancer subscale (p = 0.038), and FACT-B Total scores (p = 0.028). Tea and alcohol consumption and being very satisfied with sleep and current life were the strongest predictors of higher HRQoL in younger group. Meanwhile, no coffee consumption, frequent participation in physical activities, high sleep satisfaction, and current life satisfaction were the key predictors of higher HRQoL in older women with breast cancer. Conclusion: The relationship of the nine lifestyle habit items with HRQoL differed among younger and older women. The associated variable of low HRQoL can help clinicians take intervention early in order to improve the prognosis of patients with breast cancer.

Molecular fingerprint of precancerous lesions in breast atypical hyperplasia.

OBJECTIVE: To identify atypical hyperplasia (AH) of the breast by shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS), and to explore the molecular fingerprinting characteristics of breast AH. METHODS: Breast hyperplasia was studied in 11 hospitals across China from January 2015 to December 2016. All patients completed questionnaires on women's health. The differences between patients with and without breast AH were compared. AH breast lesions were detected by Raman spectroscopy followed by the SHINERS technique. RESULTS: There were no significant differences in clinical features and risk-related factors between patients with breast AH (n = 37) and the control group (n = 2576). Fifteen cases of breast AH lesions were detected by Raman spectroscopy. The main different Raman peaks in patients with AH appeared at 880, 1001, 1086, 1156, 1260, and 1610 cm-1, attributed to the different vibrational modes of nucleic acids, ß-carotene, and proteins. Shell-isolated nanoparticles had different enhancement effects on the nucleic acid, protein, and lipid components in AH. CONCLUSION: Raman spectroscopy can detect characteristic molecular changes in breast AH lesions, and may thus be useful for the non-invasive early diagnosis and for investigating the mechanism of tumorigenesis in patients with breast AH.

Inhibition of JAK2/STAT3 Signaling Pathway Suppresses Proliferation of Burkitt's Lymphoma Raji Cells via Cell Cycle Progression, Apoptosis, and Oxidative Stress by Modulating HSP70.

BACKGROUND The aim of this study was to investigate the effect of the JAK2/STAT3 pathway on the proliferation, cell cycle distribution, apoptosis, and oxidative stress of Raji cells via regulating HSP70 expression. MATERIAL AND METHODS Raji cells were divided into Blank, HSP70 siRNA, NC siRNA, AG490 (a JAK2/STAT3 signaling pathway inhibitor), and HSP70 siRNA + rh JAK2 (recombinant human JAK2) groups. HSP70 expression was detected by quantitative real-time reverse transcription-PCR (qRT-PCR); the expression levels of HSP70 and JAK2/STAT3 pathway-related proteins were evaluated by Western blotting; cell proliferation was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays; cell cycle distribution was observed by flow cytometry; cell apoptosis was tested by Annexin V-FITC/PI and Hoechst 33342/PI staining; reactive oxygen species (ROS) production was measured by dichloro-dihydro-fluorescein diacetate (DCFH-DA) assays; and MDA content and SOD and GSH-Px activities were determined using detection kits. RESULTS AG490 obviously down-regulated HSP70 expression, inhibited proliferation, induced cell cycle arrest at the G0/G1 phase, and promoted apoptosis in Raji cells; these effects were similar to the effects of HSP70 siRNA. Furthermore, ROS production and MDA content were increased in Raji cells treated with HSP70 siRNA or AG490, while SOD and GSH-Px activities were reduced. Raji cells in the HSP70 siRNA + rh JAK2 group did not significantly differ from those in the Blank group in regards to proliferation, cell cycle, apoptosis, and oxidative stress. CONCLUSIONS Blocking the JAK2/STAT3 signaling pathway may inhibit proliferation, induce cell cycle arrest, and promote oxidative stress and apoptosis in Raji cells via the down-regulation of HSP70.

A case-control study on risk factors of breast cancer in Han Chinese women.

This study aimed to investigate risk factors associated with breast cancer among Han Chinese women in northern and eastern China. A matched case-control study involving 1489 patients with breast cancer and 1489 controls was conducted across 21 hospitals in 11 provinces in China, from April 2012 to April 2013. We developed a structured questionnaire to record information from face-to-face interviews with participants. Student's t-tests, Pearson's chi-square tests, and univariate and multivariate conditional logistic regression analyses were used to identify variables with significant differences between the case and control groups. Ten variables were identified (P<0.05): location, economic status, waist-to-hip ratio, menopause, family history of breast cancer, present life satisfaction, sleep satisfaction, milk products, behavior prevention scores, and awareness of breast cancer. We identified a comprehensive range of factors related to breast cancer, among which several manageable factors may contribute to breast cancer prevention. Further prospective studies concerning psychological interventions, sleep regulation, health guidance, and physical exercise are required. A screening model for high-risk populations should be put on the agenda.

Isolation and characterization of adult mammary stem cells from breast cancer-adjacent tissues.

Normal adult mammary stem cells (AMSCs) are promising sources for breast reconstruction, particularly following the resection of breast tumors. However, carcinogenic events can potentially convert normal AMSCs to cancer stem cells, posing a safety concern for the use of AMSCs for clinical tissue regeneration. In the present study, AMSCs and autologous primary breast cancer cells were isolated and compared for their ability to differentiate, their gene expression profile, and their potential to form tumors in vivo. AMSCs were isolated from normal tissue surrounding primary breast tumors by immunomagnetic sorting. The pluripotency of these cells was investigated by differentiation analysis, and gene expression profiles were compared with microarrays. Differentially expressed candidate genes were confirmed by reverse transcription-polymerase chain reaction and western blot analyses. The in vivo tumorigenicity of these cells, compared with low-malignancy MCF-7 cells, was also investigated by xenograft tumor formation analysis. The results revealed that AMSCs isolated from normal tissues surrounding primary breast tumors were positive for the stem cell markers epithelial-specific antigen and keratin-19. When stimulated with basic fibroblast growth factor, a differentiation agent, these AMSCs formed lobuloalveolar structures with myoepithelia that were positive for common acute lymphoblastic leukemia antigen. The gene expression profiles revealed that, compared with cancer cells, AMSCs expressed low levels of oncogenes, including MYC, RAS and ErbB receptor tyrosine kinase 2, and high levels of tumor suppressor genes, including RB transcriptional corepressor 1, phosphatase and tensin homolog, and cyclin-dependent kinase inhibitor 2A. When injected into nude non-obese diabetic/severe combined immunodeficiency-type mice, the AMSCs did not form tumors, and regular mammary ductal structures were generated. The AMSCs isolated from normal tissue adjacent to primary breast tumors had the normal phenotype of mammary stem cells, and therefore may be promising candidates for mammary reconstruction subsequent to breast tumor resection.

A Randomized Multicenter Clinical Trial of RPH With the Simplified Milligan-Morgan Hemorrhoidectomy in the Treatment of Mixed Hemorrhoids.

PURPOSE: To explore the safety and efficacy of Ruiyun procedure for hemorrhoids (RPH) or RPH with the simplified Milligan-Morgan hemorrhoidectomy (sMMH) in the treatment of mixed hemorrhoids. METHODS: This is a randomized, controlled, balanced, multicenter study of 3000 patients with mixed hemorrhoids. The outcomes and postoperative complications were compared between 5 types of surgeries. RESULTS: The efficacy rate was the highest in patients who received RPH+sMMH and decreased in the following order: patients who received RPH alone, MMH alone, procedure for prolapse and hemorrhoids (PPH) alone, and PPH+sMMH ( P < .05). The operation time was the shortest in patients who received RPH alone and increased in the following order: patients who received RPH+sMMH, PPH alone, MMH alone, and PPH+sMMH ( P < .01). The duration of postoperative hospitalization stay was the shortest in patients who received RPH alone and increased in the following order: PPH alone, RPH+sMMH, PPH+sMMH, and MMH alone ( P < .01). The incidence of postoperative hemorrhage, uroschesis, anal fissure, crissum hematoma or thrombosis, and anorectal stenosis was significantly lower in patients who received RPH+sMMH than in patients who received the other 4 types of surgical treatments ( P < .05, P < .01). No significant differences in postoperative rectovaginal fistula and anal incontinence were observed between the 5 groups of patients. CONCLUSIONS: RPH with or without simplified MMH can reduce the incidence of postoperative complications and improve the curative efficacy in the treatment of patients with mixed hemorrhoids.

[Treatment of Mixed Hemorrhoids by RPH with the Simplified Milligan-Morgan Surgery: a Multi-center, Randomized, Controlled Clinical Trial].

Objective To observe the safety and efficacy of RPH with the simplified. Milligan-Mor- gan(M-M) surgery on mixed hemorrhoids. Methods Totally 1 200 patients with mixed hemorrhoid were assigned to the control group(600 cases) and the treatment group(600 cases) according to randomized, parallel controlled,multi-center trial design. Patients in the control group received PPH with the simplified M-M surgery, and patients in the treatment group received RPH with the simplified M-M surgery. Postop- erative complications, operation time,the postoperative hospitalization days and the efficacy were ob- served. Results Compared with the control group, the numbers of postoperation hemorrhage, postop- erative uroschesis, anal fissure and anorectal stenosis in treatment group were decreased(P <0. 01 , P < 0. 05), operation time and the postoperative hospitalization days were decreased (P <0. 01 , P <0. 05 ), the cure rate for 3 and 12 months after operation were increased (P <0. 01, P <0. 05). Conclusions RPH with the simplified M-M surgery could reduce the incidence of postoperative complications,improve the clinical cure rate and the curative effect in treatment of mixed hemorrhoids.

Circulating High-Molecular-Weight (HMW) Adiponectin Level Is Related with Breast Cancer Risk Better than Total Adiponectin: A Case-Control Study.

The level of total adiponectin, a mixture of different adiponectin forms, has been reported associated with breast cancer risk with inconsistent results. Whether the different forms play different roles in breast cancer risk prediction is unclear. To examine this, we measured total and high molecular weight (HMW) adiponectin in a case-control study (1167 sets). Higher circulating HMW adiponectin was negatively associated with breast cancer risk after adjusting for menopausal status and family history of breast cancer (P=0.024). We analyzed the relationship between adiponectin and breast cancer risk in 6 subgroups. Higher circulating HMW adiponectin was also negatively associated with breast cancer risk (P=0.020, 0.014, 0.035) in the subgroups of postmenopausal women, negative family history of breast cancer, BMI>=24.0. Total adiponectin was positively associated with breast cancer (P=0.028) in the subgroup of BMI<=24.0. Higher HMW/total adiponectin ratio was negatively associated with breast cancer (P=0.019) in the subgroup of postmenopausal women. Interestingly, in the subgroup of women with family history of breast cancer, higher circulating total and HMW adiponectin were positively associated with breast cancer risk (P=0.034, 0.0116). This study showed different forms of circulating adiponectin levels might play different roles in breast cancer risk. A higher circulating HMW adiponectin is associated with a decreased breast cancer risk, especially in postmenopausal, without family history of breast cancer or BMI>=24.0 subgroups, whereas higher circulating HMW adiponectin levels is a risk factor in women with a family history of breast cancer. Further investigation of different forms of adiponectin on breast cancer risk is needed.

The expression of aldehyde dehydrogenase 1 in invasive primary breast tumors and axillary lymph node metastases is associated with poor clinical prognosis.

The enzyme aldehyde dehydrogenase 1 (ALDH1) has been reported as a biomarker for identifying cancer stem cells. Previous studies have shown that ALDH1 expression in primary breast cancers was associated with poor clinical prognosis. In this study, we aimed to determine whether ALDH1 expression in axillary lymph node metastases (ALNM) of breast cancer patients was also associated with poor prognosis. Expression of ALDH1, ER, PgR, HER2 and KI-67 was examined in primary tumors and ALNM of 161 patients with invasive breast cancer. Survival analysis and multivariate analysis were used to determine the relationship between ALDH1 expression and clinical prognosis. Patients with positive ALDH1 expression in primary tumors and in ALNM had significantly shorter relapse-free survival (RFS) times and overall survival (OS) times compared to those whose tissues were ALDH1 negative. ALDH1-positivity in primary tumors was significant both in univariate and multivariate analyses of RFS and OS. ALDH1 expression in ALNM was significant in a univariate analysis of RFS and OS but not in a multivariate analysis of RFS and OS. We conclude that the expression of ALDH1 in primary breast tumors or ALNM may be one potential risk factor for poor, long-term outcomes.

[Expression of translationally controlled tumor protein in human breast cancer and its clinical significance].

OBJECTIVE: To investigate the expression of translationally controlled tumor protein (TCTP) in human breast cancer tissues and its clinical significances. METHODS: The expression of TCTP in 94 human breast cancer and the corresponding adjacent normal mammary tissues were detected using immunohistochemistry. RESULTS: The expression rate of TCTP was 64.89% in human breast cancer tissues, significantly higher than that in normal benign mammary tissues (39.36%, P<0.001). TCTP overexpression was positively correlated to the tumor size, clinical stage, lymph node metastasis and histological grade of breast cancer (P<0.05). Patients with positive TCTP expression had a significantly shorter mean survival time than those with negative expression (P<0.001). CONCLUSION: TCTP may play an important role in the tumorigenesis and development of breast cancer, and can be an important prognostic factor for this malignancy.

[Influence of microsatellite instability on survival of patients with sporadic colorectal cancer in China].

OBJECTIVE: To investigate the role of microsatellite instability(MSI) in Chinese sporadic coloretal cancer. METHODS: A total of 146 patients with colorectal cancer were treated surgically from August 2004 to September 2006 in the Third Affiliated Hospital of Nanjing University of Traditional Chinese Medicine. Data were collected prospectively. Univariate and multivariable analyses were performed for parameters such as age, gender, tumor location, differentiation, MSI, tumor type, lymph node metastasis, TNM stage, and survival. RESULTS: Follow-up was available in 134 patients including telephone call and office visit. MSI(P=0.029), tumor type(P=0.000), TNM stage(P=0.000) were independently associated with survival on Cox regression model. There were 26 patients with MSI, and the 1-, 3-, and 5-year survival rates were 100%, 92.3%, and 92.3%, respectively. The remaining 108 patients had microsatellite stable tumor, and the 1-, 3-, and 5-year survival rates were 96.3%, 72.2%, and 63.5%, respectively. The difference was statistically significant(P=0.016). CONCLUSION: Microsatellite instability is an important factor associated with patient survival in Chinese sporadic colorectal cancer.

Ca2+-binding protein S100A11: a novel diagnostic marker for breast carcinoma.

To evaluate whether S100A11 could be considered to be a novel diagnostic marker in breast carcinoma, the method of differential proteomics, Western blotting, and immunohistochemistry were used to detect the expression pattern and subcellular localization of S100A11. Statistical analyses indicated that specific up-regulated of A100A11 did not correlate with other prognostic factors such as age, tumor size, grade and stage, ER, PR, HER-2 and nodal status. Our data support that S100A11 is a novel diagnostic marker in breast carcinoma. Analysis of S100A11 expression in breast cancer may be an effective tool help in detection of early-stage breast cancer.

[Study of germline mutation of hMSH2, hMSH6 and hMLH1 and methylation of hMLH1 in microsatellite instability colorectal cancer].

OBJECTIVE: To study the characteristics of germline mutations of hMLH1, hMSH2 and hMSH6 and promoter methylation status of MLH1 in patients with MSI colorectal cancer. METHODS: Sequence analysis of germline mutation and promoter methylation of MLH1 in 34 prospective collected patients with MSI colorectal cancer were performed. RESULTS: Nineteen out of 34 patients with MSI colorectal cancer were detected with hypermethylation of MLH1,which accounted for 55.9%. 73.7% MSI-H colorectal cancer cases and 33.3% MSI-L colorectal cancer cases were detected with hypermethylation of MLH1 and the difference was significant. Eight germline mutations were found, including 3 MSH6 mutations and 5 MSH2 mutations. CONCLUSION: There are some different characteristics of the germline mutations of hMLH1, hMSH2 and hMSH6 and promoter methylation of MLH1 in Chinese MSI colorectal patients.

[Total mastectomy and axillary dissection with conservation of the nipple-areola complex, and immediate reconstruction with artificial prosthesis in the treatment of early breast cancer].

OBJECTIVE: To study the feasibility of total mastectomy and axillary dissection with conservation of the nipple-areola complex, and immediate reconstruction with artificial prosthesis in the treatment of early breast cancer. METHODS: The 20 patients with breast cancer (TNM stage I, 6 patients; stage II, 14 patients) underwent the total mastectomy axillary dissection with conservation of the nipple-areola complex, and immediate reconstruction with artificial prosthesis. Post-operation they were given chemotherapy, radiotherapy, endocrine therapy. RESULTS: The mean follow-up for the entire group of 20 patients was 52.3 months, eighteen patients were more than 36 months. All patients were still alive, without local or regional recurrences. One patient suffered from multiple metastasis of liver and bone nine months after the operation, who has living five years now. CONCLUSION: Total mastectomy and axillary dissection with conservation of the nipple-areola complex, and immediate reconstruction with artificial prosthesis on selected patients with breast cancer is an oncologically acceptable procedure with superior cosmetic results, without increasing the risk of local recurrences, complications and influencing the effects of postoperative adjuvant treatment.