[The prognostic value of morphological and functional parameters of cardiac magnetic resonance in patients with systemic light chain amyloidosis].

Objective: To investigate the features of morphological and functional parameters of cardiac magnetic resonance (CMR) in patients with systemic light chain (AL) amyloidosis, and the prognostic values of these related parameters. Methods: The data of 97 patients (including 56 males and 41 females, aged 36 to 71 years) with AL amyloidosis from April 2016 to August 2019 in the General Hospital of Eastern Theater Command were retrospectively analyzed. All patients underwent CMR examination. Those patients were divided into survival (n=76) and death groups (n=21) according to the clinical outcomes, and the differences in clinical baseline and CMR parameters between the two groups were analyzed and compared. A smooth curve fitting was used to analyze the association between morphological and functional parameters and extracellular volume (ECV), and Cox regression models were conducted to explore the association between related parameters and mortality. Results: The left ventricular global function index (LVGFI), myocardial contraction fraction (MCF) and stroke volume index (SVI) decreased with increasing ECV [ß (95%CI) was -0.566 (-0.685--0.446), -1.201 (-1.424--0.977), -0.149 (-0.293--0.004), respectively;all P<0.05]. Left ventricular mass index (LVMI), and diastolic left ventricular global peak wall thickness (LVGPWT) increased with increasing ECV [ß(95%CI) was 1.440 (1.142-1.739), 0.190 (0.147-0.233), respectively;both P<0.001]. While left ventricular ejection fraction (LVEF) began to decrease only at higher amyloid burden (ß=-0.460, 95%CI:-0.639--0.280, P<0.001). The median follow-up time was 39 months (range 2-64 months), and 21 patients died during the follow-up period. The estimated survival rates according to Kaplan-Meier curves at 1, 3, and 5 years were 92.8%, 78.7%, and 77.1%, respectively. MCF<39% (HR=10.266, 95%CI: 4.093-25.747) and LVGFI<26% (HR=9.267, 95%CI: 3.705-23.178) were independent risk factors for death in patients with AL amyloidosis after adjusting for other CMR parameters (P<0.001). Conclusion: Multiple morphologic and functional parameters of CMR vary with the increase of ECV. MCF<39% and LVGFI<26% were independent risk factors for death.

[A comparative study of breast cancer mass screening and opportunistic screening in Chinese women].

Objective: To compare the population characteristics, the positive rate of screening, the detection rate of breast cancer, early diagnosis rate and the cost between the mass screening group and opportunistic screening group of breast cancer. Methods: This study is a prospective multicenter cohort study conducted from January 1, 2014 to December 31, 2016. The participants were enrolled for mass screening or opportunistic screening of breast cancer. After completing the questionnaire, all the participants received breast physical examination and breast ultrasound examination every year for 3 rounds by year. The participants' characteristics and screening results of the two groups were compared by χ2 test, Fisher exact test or Wilcoxon rank-sum test. Results: A total of 20 080 subjects were enrolled. In the mass screening group, 9 434 (100%), 8 111 (85.98%) and 3 940 (41.76%) cases completed the 3 rounds of screening, and 10 646 (100%), 6 209 (58.32%) and 2 988 (28.07%) cases in the opportunistic screening group, respectively. In the opportunistic screening group, the proportions of less than 3 months lactation (1 275/9 796 vs. 1 061/8 860, χ²=4.597, P=0.032), non-fertility (850/10 646 vs. 574/9 434, χ²=27.400, P<0.01), abortion history (6 384/10 646 vs. 5 062/9 434, χ²=81.232, P<0.01), postmenopausal (2 776/10 646 vs. 2 217/9 434, χ²=17.757, P<0.01), long-term oral contraceptives(>6 months) (171/10 646 vs. 77/9 434, χ²=25.593, P<0.01) and family history of breast cancer in first-degree relatives (464/10 646 vs. 236/9 434, χ²=51.257, P<0.01) were significantly higher than those in mass screening group. The positive rate of screening (514/10 646 vs. 128/9 434, χ²=194.736, P<0.01), the detection rate of breast cancer (158/10 646 vs. 13/9 434, χ²=107.374, P<0.01), and positive rate of biopsy (158/452 vs. 13/87, χ²=13.491, P<0.01) in the opportunistic screening group were significantly higher than those of the mass screening group. The early diagnosis rate of the mass screening group was significantly higher than the opportunistic screening group (10/12 vs. 66/141, χ²=5.902, P=0.015). The average cost for detecting each breast cancer case of the mass screening group was 215 038 CNY, which was 13.6 times of the opportunistic screening group (15 799 CNY/case). In the opportunistic screening group, the positive rate of biopsy in primary hospitals was significantly lower than that in large-volume hospitals (79/267 vs. 79/185, χ²=8.267, P=0.004), but there was no significant difference in the mass screening group (6/37 vs. 7/50, χ²=0.082, P=0.774). Conclusions: Breast cancer screening can improve early detection rate. Compared with the mass screening mode, the opportunistic screening mode has the advantages of higher proportion of high-risk factors, higher positive rate of screening, higher detection rate of breast cancer, higher positive rate of biopsy, and lower cost of screening. However, the early diagnosis rate of breast cancer of opportunistic screening is lower than that of mass screening. The positive rate of opportunistic screening in primary hospitals is lower than that of large-volume hospitals. The two screening modes have their own advantages and should be chosen according to local conditions of different regions in China.

Analysis of radiotherapy optimization regimens after modified radical mastectomy.

OBJECTIVE: Concomitant chemo-radiotherapy after modified radical mastectomy for breast cancer is an effective means of achieving high survival rates. In this study different radiotherapy optimization regimens are compared to assess their effectiveness and toxicity rates. PATIENTS AND METHODS: 112 patients with modified radical mastectomy participated, and were randomly assigned to one of three groups, all receiving adjuvant chemotherapy for 4-6 weeks prior to radiotherapy: group A received intensity modulated radiotherapy (radiation dose (DT) 50 Gy, 2.0 Gy/fraction, 25 times, during the course of 33-35 days); group B received concurrent radio chemotherapy and intensity modulated radiotherapy; and group C adopted concurrent radio chemotherapy and hypofractionation (DT of 42.56 Gy, 2.66Gy/fraction, 16 times, during the course of 22-24 days) with 37 cases. The occurrence of acute and chronic radiation injuries, the cancer recurrence and the survival rates were compared, and a dose volume histogram (DVH) was created. RESULTS: The total prevalence and survival rates of Group C were significantly better than those of the other two groups (p ≤ 0.05); in spite of the fact that the local recurrence and distant metastasis rates separately were all statistically the same (p ≥ 0.05). Also, the total radiation injury occurrence of group C was significantly lower (p < 0.05); but no significant differences were found when singling out acute and chronic injury occurrences or injury severity between the three groups. The values of V5, V10, V20 and V30 increased gradually in all of the groups, and V5 and V10 in Group C were higher than those in the other two groups, but the comparison between V20 and V30 yielded no statistically significant differences. CONCLUSIONS: Based on these results, the concurrence of hypo-fractionation radiotherapy and chemotherapy may be an effective and safe approach for cancer treatment after modified radical mastectomy, and larger studies are warranted given the convenience of the method.

Stromal matrix metalloproteinase-11 is involved in the mammary gland postnatal development.

MMP-11 is a bad prognosis paracrine factor in invasive breast cancers. However, its mammary physiological function remains largely unknown. In the present study we have investigated MMP-11 function during postnatal mammary gland development and function using MMP-11-deficient (MMP-11-/-) mice. Histological and immunohistochemical analyses as well as whole-mount mammary gland staining show alteration of the mammary gland in the absence of MMP-11, where ductal tree, alveolar structures and milk production are reduced. Moreover, a series of transplantation experiments allowed us to demonstrate that MMP-11 exerts an essential local paracrine function that favors mammary gland branching and epithelial cell outgrowth and invasion through adjacent connective tissues. Indeed, MMP-11-/- cleared fat pads are not permissive for wild-type epithelium development, whereas MMP-11-/- epithelium transplants grow normally when implanted in wild-type cleared fat pads. In addition, using primary mammary epithelial organoids, we show in vitro that this MMP-11 pro-branching effect is not direct, suggesting that MMP-11 acts via production/release of stroma-associated soluble factor(s). Finally, the lack of MMP-11 leads to decreased periductal collagen content, suggesting that MMP-11 has a role in collagen homeostasis. Thus, local stromal MMP-11 might also regulate mammary epithelial cell behavior mechanically by promoting extracellular matrix stiffness. Collectively, the present data indicate that MMP-11 is a paracrine factor involved during postnatal mammary gland morphogenesis, and support the concept that the stroma strongly impact epithelial cell behavior. Interestingly, stromal MMP-11 has previously been reported to favor malignant epithelial cell survival and promote cancer aggressiveness. Thus, MMP-11 has a paracrine function during mammary gland development that might be harnessed to promote tumor progression, exposing a new link between development and malignancy.

REGγ is a strong candidate for the regulation of cell cycle, proliferation and the invasion by poorly differentiated thyroid carcinoma cells

REGγ is a proteasome activator that facilitates the degradation of small peptides. Abnormally high expression of REGγ has been observed in thyroid carcinomas. The purpose of the present study was to explore the role of REGγ in poorly differentiated thyroid carcinoma (PDTC). For this purpose, small interfering RNA (siRNA) was introduced to down-regulate the level of REGγ in the PDTC cell line SW579. Down-regulation of REGγ at the mRNA and protein levels was confirmed by RT-PCR and Western blot analyses. FACS analysis revealed cell cycle arrest at the G1/S transition, the MTT assay showed inhibition of cell proliferation, and the Transwell assay showed restricted cell invasion. Furthermore, the expression of the p21 protein was increased, the expression of proliferating cell nuclear antigen (PCNA) protein decreased, and the expression of the p27 protein was unchanged as shown by Western blot analyses. REGγ plays a critical role in the cell cycle, proliferation and invasion of SW579 cells. The alteration of p21 and PCNA proteins related to the down-regulation of REGγ suggests that p21 and PCNA participate in the process of REGγ regulation of cell cycle progression and cell proliferation. Thus, targeting REGγ has a therapeutic potential in the management of PDTC patients.

REGγ is a strong candidate for the regulation of cell cycle, proliferation and the invasion by poorly differentiated thyroid carcinoma cells.

REGγ is a proteasome activator that facilitates the degradation of small peptides. Abnormally high expression of REGγ has been observed in thyroid carcinomas. The purpose of the present study was to explore the role of REGγ in poorly differentiated thyroid carcinoma (PDTC). For this purpose, small interfering RNA (siRNA) was introduced to down-regulate the level of REGγ in the PDTC cell line SW579. Down-regulation of REGγ at the mRNA and protein levels was confirmed by RT-PCR and Western blot analyses. FACS analysis revealed cell cycle arrest at the G1/S transition, the MTT assay showed inhibition of cell proliferation, and the Transwell assay showed restricted cell invasion. Furthermore, the expression of the p21 protein was increased, the expression of proliferating cell nuclear antigen (PCNA) protein decreased, and the expression of the p27 protein was unchanged as shown by Western blot analyses. REGγ plays a critical role in the cell cycle, proliferation and invasion of SW579 cells. The alteration of p21 and PCNA proteins related to the down-regulation of REGγ suggests that p21 and PCNA participate in the process of REGγ regulation of cell cycle progression and cell proliferation. Thus, targeting REGγ has a therapeutic potential in the management of PDTC patients.

A novel single nucleotide polymorphism of the cyclooxygenase-2 gene associated with breast cancer.

AIMS: Cyclooxygenase-2 (COX-2) is involved in carcinogenesis, immune response suppression, apoptosis inhibition, angiogenesis, and tumour cell invasion and metastasis. The gene for COX-2, designated as PTGS2, carries several polymorphisms, such as -765G >C, 1195G/A in the promoter region, and 8473T >C in the 3' UTR, which have been associated with susceptibility to malignant disease. The aim of this study was to search for new mutations and polymorphisms in the COX-2 gene and to assess the relationship with breast cancer. MATERIALS AND METHODS: In the present study, we identified a novel single nucleotide polymorphism, 169C >G, in exon 2 using polymerase chain reaction-single-strand conformation polymorphism analysis. This nucleotide change causes the amino acid change from proline to alanine at codon 57. To investigate the role of this polymorphism for breast cancer, we determined the prevalence of PTGS2 genotypes in 310 women with breast cancer and 310 gender- and age-matched healthy control subjects. RESULTS: Homozygous carriers of the 169-GG genotype were more frequent among patients (15.16%) than among controls (9.35%; P = 0.03). The odds ratio for carriers of this genotype for breast cancer was 1.76 (95% confidence interval, 1.20-3.05). Among patients, oestrogen receptor positivity was less frequent among carriers of a GG genotype (61.7%) than among carriers of a CC or GC genotype (72.3%; P = 0.02). Tumour size, histological grade, presence of primary lymph node metastases, progesterone receptor positivity, or age at diagnosis were not associated with PTGS2 genotypes. CONCLUSION: We conclude that the homozygous PTGS2 169-GG genotype may be associated with breast cancer risk.

Neuroendocrine primary small cell carcinoma of the breast. Report of a case and review of the literature.

One case of breast neuroendocrine primary small cell carcinoma with light microscopic and immunohistochemical findings is reported. The patient died of unrelated disease 21 months after diagnosis and treatment by modified radical mastectomy, radiotherapy and subsequent chemotherapy. Immunohistochemical studies revealed cytokeratin and neuroendocrine markers (chromogranin, neuron-specific enolase) immunostaining on tumoral cells. Expression for neuropeptides (met-enkephalin, leu-enkephalin, beta-endorphin) and CALLA antigen was found. Based on this case report and six other previously reported cases, breast neuroendocrine primary small cell carcinoma appears to be a very aggressive tumor for which no firm conclusions regarding treatment can be drawn.