Diagnostic accuracy of pre-operative breast magnetic resonance imaging (MRI) in predicting axillary lymph node metastasis: variations in intrinsic subtypes, and strategy to improve negative predictive value-an analysis of 2473 invasive breast cancer patients.

BACKGROUND: The value and utility of axillary lymph node (ALN) evaluation with MRI in breast cancer were not clear for various intrinsic subtypes. The aim of the current study is to test the potential of combining breast MRI and clinicopathologic factors to identify low-risk groups of ALN metastasis and improve diagnostic performance. MATERIAL AND METHODS: Patients with primary operable invasive breast cancer with pre-operative breast MRI and post-operative pathologic reports were retrospectively collected from January 2009 to December 2021 in a single institute. The concordance of MRI and pathology of ALN status were determined, and also analyzed in different intrinsic subtypes. A stepwise strategy was designed to improve MRI-negative predictive value (NPV) on ALN metastasis. RESULTS: 2473 patients were enrolled. The diagnostic performance of MRI in detecting metastatic ALN was significantly different between intrinsic subtypes (p = 0.007). Multivariate analysis identified tumor size and histologic type as independent predictive factors of ALN metastases. Patients with HER-2 (MRI tumor size ≤ 2 cm), or TNBC (MRI tumor size ≤ 2 cm) were found to have MRI-ALN-NPV higher than 90%, and these false cases were limited to low axillary tumor burden. CONCLUSION: The diagnostic performance of MRI to predict ALN metastasis varied according to the intrinsic subtype. Combined pre-operative clinicopathologic factors and intrinsic subtypes may increase ALN MRI NPV, and further identify some groups of patients with low risks of ALN metastasis, high NPV, and low burdens of axillary disease even in false-negative cases.

Alpinate Oxyphyllae extracts enhance the longevity and homing of mesenchymal stem cells and augment their protection against senescence in H9c2 cells.

Adipose-derived mesenchymal stem cells (ADMSCs) are easily accessible and are attractive mesenchymal stem cells for use in regenerative medicine; however their application is frequently restricted due to various challenges present in the environment they are administered. Therefore ADMSCs are preferably preconditioned with various stimulating factors to overcome the barriers developed in any pathological conditions. Here we used ADMSCs from rat adipose based on the abundance of positive markers and preconditioned the cells with extracts from Alpinate Oxyphyllae Fructus (AOF), a traditional Chinese herb used for antiaging, associated various health benefits. The preconditioned stem cells were tested for their potential to drive H9c2 from doxorubicin (Dox)-induced aging. The AOF-treated stem cells enriched stemness in ADMSCs with respect to their stem cells' positive marker, and enhanced their longevity mechanism and elevated the stem cell homing-associated C-X-C chemokine receptor type 7 (CXCR7). The AOF preconditioned stem cells, when cocultured with H9c2 cells, showed effective protection to Dox-induced senescence and stem cell homing to damaged H9c2 cells. The presence of AOF provided greater protective effects in the Dox environment. In addition, AOF-pretreated ADMSCs showed enhanced migration than those treated with AOF in Dox environment. Therefore, our results show that administration of AOF preconditioned stem cells is potentially an effective strategy in the management of aging-associated cardiac disorders.

Cryptotanshinone (Dsh-003) from Salvia miltiorrhiza Bunge inhibits prostaglandin E2-induced survival and invasion effects in HA22T hepatocellular carcinoma cells.

Human hepatocellular carcinoma (HCC) is currently the second most common cancer and one of the leading causes of cancer-related mortality in Taiwan. Previous reports show that the expression of (E-type prostaglandin 2) EP2 and (E-type prostaglandin 4) EP4 are elevated in HCC and further demonstrate that Prostaglandin E2 (PGE2) induces HA22T cell proliferation and metastasis through EP2 and EP4 receptor. Danshen (root of Salvia miltiorrhiza Bunge) is a very important and popular traditional Chinese herbal medicine which is widely and successfully used against breast cancer, leukemia, pancreatic cancer, and head and neck squamous carcinoma cells. In this study, we used Cryptotansinone (Dsh-003) (MW 269.14) from Danshen to investigate their effect and corresponding mechanism of action in PGE2-treated HA22T cells. Dsh-003 inhibited HA22T cell viability and further induced cell apoptosis in PGE2-treated HA22T cells. Furthermore, Dsh-003 inhibited EP2, EP4, and their downstream effector such as p-PI3K and p-Akt expression in HA22T hepatocellular carcinoma cells. We also observed that Dsh-003 blocked PGE2-induced cell migration by down-regulating PGE2-induced ß-catenin expression and by up-regulating E-cadherin and GSK3-ß expression. All these findings suggest that Dsh-003 inhibit human HCC cell lines and could potentially be used as a novel drug for HCC treatment.

Epigenetic changes in tumor suppressor genes, P15, P16, APC-3 and E-cadherin in body fluid.

The inactivation of tumor suppressor genes by promoter methylation plays an important role in the development of cancers; it can also be used as a marker to distinguish cancerous cells from non-cancer cells. In this study, we investigated the aberrant methylation profile of the tumor suppressor genes P15, P16, APC and E-cadherin in the cells of body fluid. A methylation-specific polymerase chain reaction was performed in 31 cases of malignant effusion and 39 cases of non-malignant effusion. Aberrant promoter methylation of P15, P16, APC and E-cadherin genes was seen in 0%, 25.8%, 35.5% and 6.5% of malignant effusion cases, respectively, whereas the frequencies were 0%, 2.6%, 2.6% and 0%, respectively, for negative control effusion. There were statistically significant differences in the aberrant methylation of P16 (p = 0.008) and APC (p = 0.018) genes between cases of malignant effusion and controls. Methylation of one of three genes (P16, E-cadherin, APC) was found in 14 out of 31 (45.2%) cases of malignant effusion, and in two out of 39 (5.1%) cases of non-malignant effusion (p = 0.000004). Concurrent methylation was found in nine out of 31 (29%) cases of malignant effusion, but in no non-malignant effusion sample. From these results, we suggest that methylation-specific polymerase chain reaction to analyze the promoters of tumor suppressor genes can distinguish between malignant effusion and benign effusion, and may help cytologists to make more accurate diagnoses.

Expression of c-kit protooncogene in human hepatocellular carcinoma.

The expression of the c-kit protooncogene in human hepatocellular carcinoma (HCC) was investigated. Immunohistochemical staining (IHC) and RT-PCR were employed to examine the protein and mRNA expression of c-kit protooncogene, respectively. IHC results demonstrated that 22 of 86 (25.6%) HCC tissue sections expressed c-kit protein. The c-kit mRNA transcript was further confirmed in all 22 IHC c-kit positive HCC tissue samples by RT-PCR. Moreover, the relationship between c-kit expression in HCC and prognosis of patients was statistically analyzed and a correlation was established. The group of patients whose HCC specimens showed positive c-kit staining exhibited better survival as compared to those patients with negative c-kit expression (p=0.021). These results suggest that c-kit expression may be a good prognostic indicator for HCC.