Ganglioside GD2 Expression Is Associated With Unfavorable Prognosis in Early Triple-negative Breast Cancer.

BACKGROUND/AIM: Gangliosides (acidic glycosphingolipids) have crucial regulatory roles in normal physiological processes, as well as in pathological conditions, including tumor onset and progression. GD2 is highly expressed in triple-negative breast cancer (TNBC), particularly in cancer stem cells. However, little is known on the clinical impact of GD2 expression on the prognosis of TNBC. Consequently, we aimed to investigate the association between GD2 expression in TNBC and the prognosis of TNBC. PATIENTS AND METHODS: We assessed GD2 expression in 76 patients with primary TNBC who had undergone surgery at our Institute between 2012 and 2015 using immunohistochemical analysis with a tissue microarray technique. We investigated the relationship between GD2 expression and clinicopathological factors in TNBC, recurrence-free survival (RFS), and overall survival (OS). RESULTS: Increased GD2 expression was observed in 45% of TNBC patients. There was no significant association between GD2 expression and clinicopathological factors in TNBC. The 5-year RFS rate among patients with GD2-positive TNBCs was significantly worse than that among patients with GD2-negative TNBCs (75.4% and 94.9%; HR=4.931; 95%CI=1.024-23.752; p=0.027). The OS in patients with GD2-positive TNBCs tended to be inferior to that of patients with GD2-negative TNBCs (HR=5.357; 95%CI=0.599-47.939; p=0.092). Interestingly, in patients with GD2-positive TNBCs, a higher grade of tumor-infiltrating lymphocytes (TILs) displayed a significantly better impact on OS (TILs-high vs. TILs-low; p=0.04). Both univariate and multivariate analyses showed that GD2 expression negatively affected RFS (p=0.027, p=0.021, respectively). CONCLUSION: GD2 expression is an independent unfavorable prognostic factor for TNBC.

Preferences Regarding Breast Surgery Omission Among Patients With Breast Cancer Who Receive Neoadjuvant Chemotherapy.

BACKGROUND/AIM: Currently, several ongoing prospective studies are investigating the safety of breast surgery omission in patients with breast cancer who are exceptional responders to neoadjuvant chemotherapy. However, there is little information about the preferences of these patients regarding omission of breast surgery. PATIENTS AND METHODS: We conducted a questionnaire survey to assess preferences regarding omission of breast surgery among patients with breast cancer who had human epidermal growth factor receptor 2-positive or estrogen receptor-negative tumors and good clinical response after neoadjuvant chemotherapy. Patients' estimation of the risk of ipsilateral breast tumor recurrence (IBTR) after definitive surgery or breast surgery omission was also assessed. RESULTS: Of 93 patients, only 22 (23.7%) said they would omit breast surgery. Under the scenario of omitting breast surgery, the 5-year IBTR rate estimated by patients who said they would omit breast surgery was significantly lower (median, 10%) than the rate estimated by patients who preferred undergoing definitive surgery (median, 30%) (p=0.017). CONCLUSION: The proportion of our surveyed patients who were willing to omit breast surgery was low. Patients who said they preferred to omit breast surgery overestimated the 5-year IBTR risk.

Long-term course of the changes in the nipple position after breast-conserving surgery.

PURPOSE: Even if favorable cosmetic outcomes are obtained shortly after breast-conserving surgery (BCS), cosmetic changes may occur up to several years after BCS. In the present study, we evaluated cosmetic changes while focusing on changes in the nipple position after BCS. METHODS: We examined the long-term course of changes in the nipple position over time after BCS using the proportion of the distance between the sternal notch and nipple (PDSN) in 196 patients. We also evaluated risk factors for long-term nipple position changes. RESULTS: The median follow-up period was 9.9 years. Nipple position changes occurred within eight years after BCS and seemed to plateau beyond that point. The body mass index (BMI), breast size, proportion of excision volume and axillary treatment were significantly associated with the nipple position changes within one to five years after BCS. The BMI, breast size, axillary treatment, chemotherapy and hormonal therapy were significantly associated with the nipple position changes within five to eight years after BCS. CONCLUSIONS: After BCS, the nipple position changes occur within about eight years. Obesity, large breast size, large excision volume, axillary treatment, chemotherapy and hormone therapy were factors that affected the treated breast shrinkage and increase in the left-right difference after BCS.

Antimicrobial cathelicidin peptide LL­37 induces NET formation and suppresses the inflammatory response in a mouse septic model.

LL­37 is the only known member of the cathelicidin family of antimicrobial peptides in humans. In addition to its broad spectrum of antimicrobial activities, LL­37 may modulate various inflammatory reactions. The authors previously revealed that LL­37 improves the survival of a murine cecal ligation and puncture (CLP) sepsis model. In the present study, the mechanism for the protective action of LL­37 was elucidated using the CLP model, focusing on the effect of LL­37 on the release of neutrophil extracellular traps (NETs). The results indicated that the intravenous administration of LL­37 suppressed the increase of damage-associated molecular patterns (DAMPs), including histone­DNA complex and high­mobility group protein 1, in addition to interleukin­1ß, tumor necrosis­α and soluble triggering receptor expressed on myeloid cells (TREM)­1 in plasma and peritoneal fluids. Notably, LL­37 significantly suppressed the decrease of mononuclear cell number in blood, and the increase of polymorphonuclear cell (neutrophil) number in the peritoneal cavity during sepsis. Furthermore, LL­37 reduced the bacterial burden in blood and peritoneal fluids. Notably, LL­37 increased the level of NETs (myeloperoxidase­DNA complex) in plasma and peritoneal fluids. In addition, it was verified that LL­37 induces the release of NETs from neutrophils, and NETs possess the bactericidal activity. Overall, these observations suggest that LL­37 improves the survival of CLP septic mice by possibly suppressing the inflammatory responses as evidenced by the inhibition of the increase of cytokines, soluble TREM­1 and DAMPs (host cell death) and the alteration of inflammatory cell numbers, and bacterial growth via the release of NETs with bactericidal activity.

The gross motor function measure is valid for Fukuyama congenital muscular dystrophy.

Fukuyama congenital muscular dystrophy (FCMD) is the second most common muscular dystrophy in Japan. FCMD is an autosomal recessive disorder caused by mutations in the fukutin gene. The main features of FCMD are a combination of infantile-onset hypotonia, generalized muscle weakness, eye abnormalities, and mental retardation associated with cortical migration defects, and most patients are never able to walk. To date, the development of a quantitative motor scale for FMCD has been difficult due to the moderate-to-severe intellectual impairment that accompanies FCMD. Gross motor function measure (GMFM), originally developed as a quantitative motor scale for cerebral palsy, can precisely and quantitatively assess motor function without complicated instructions, and was recently reported to be useful in the assessment of Down syndrome and spinal muscular atrophy. To confirm the validity of GMFM for the assessment of FCMD, 41 FCMD patients (age range: 0.6-24.4 years) were recruited for this study. The GMFM scores correlated significantly with those of two previously used motor scales, and the time-dependent change in GMFM scores was consistent with the natural course of FCMD. The inter-rater reliability, based on determinations made by four physiotherapists blinded to each other's assessment results, was excellent. We concluded GMFM to be a useful and valid measure of motor function in FCMD patients.