Star-related lipid transfer protein 10 (STARD10): a novel key player in alcohol-induced breast cancer progression.

BACKGROUND: Ethanol abuse promotes breast cancer development, metastasis and recurrence stimulating mammary tumorigenesis by mechanisms that remain unclear. Normally, 35% of breast cancer is Erb-B2 Receptor Tyrosine Kinase 2 (ERBB2)-positive that predisposes to poor prognosis and relapse, while ethanol drinking leads to invasion of their ERBB2 positive cells triggering the phosphorylation status of mitogen-activated protein kinase. StAR-related lipid transfer protein 10 (STARD10) is a lipid transporter of phosphatidylcholine (PC) and phosphatidylethanolamine (PE); changes on membrane composition of PC and PE occur before the morphological tumorigenic events. Interestingly, STARD10 has been described to be highly expressed in 35-40% of ERBB2-positive breast cancers. In this study, we demonstrate that ethanol administration promotes STARD10 and ERBB2 expression that is significantly associated with increased cell malignancy and aggressiveness. MATERIAL AND METHODS: We investigated the effect of ethanol on STARD10-ERBB2 cross-talk in breast cancer cells, MMTV-neu transgenic mice and in clinical ERBB2-positive breast cancer specimens with Western Blotting and Real-time PCR. We also examined the effects of their knockdown and overexpression on transient transfected breast cancer cells using promoter activity, MTT, cell migration, calcium and membrane fluidity assays in vitro. RESULTS: Ethanol administration induces STARD10 and ERBB2 expression in vitro and in vivo. ERBB2 overexpression causes an increase in STARD10 expression, while overexpression of ERBB2's downstream targets, p65, c-MYC, c-FOS or c-JUN induces STARD10 promoter activity, correlative of enhanced ERBB2 function. Ethanol and STARD10-mediated cellular membrane fluidity and intracellular calcium concentration impact ERBB2 signaling pathway as evaluated by enhanced p65 nuclear translocation and binding to both ERBB2 and STARD10 promoters. CONCLUSION: Our finding proved that STARD10 and ERBB2 positively regulate each other's expression and function. Taken together, our data demonstrate that ethanol can modulate ERBB2's function in breast cancer via a novel interplay with STARD10.

Surgical treatment of severe hidradenitis suppurativa of the axilla: thoracodorsal artery perforator (TDAP) flap versus split skin graft.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, inflammatory disease affecting the apocrine glands of the axillary, groin and mammary regions with significant physical and psychosocial sequelae. Surgical excision of the affected tissue is the gold standard treatment. Severe axillary HS is associated with high rates of recurrence and requires extensive surgical resection with challenging reconstruction associated with risk of post-operative complications. The most effective method for reconstruction of the axilla after excision of HS is yet to be identified. We present a prospective observational study comparing thoraco-dorsal artery perforator (TDAP) flap and split-skin graft (SSG). METHODS: Over 4 years, we enrolled 27 consecutive patients with Hurley's Stage III HS of the axilla who underwent surgical excision with reconstruction using either SSG (n=12) or TDAP flap reconstruction (n=15). We evaluated and compared intraoperative and post-operative data, quality of life (dermatology life quality index questionnaire) and pain/discomfort (visual analogue scale) before and after surgery. RESULTS: Patients who underwent TDAP flap reconstruction had significantly faster recovery, fewer complications and fewer overall number of procedures than those who underwent SSG reconstruction. All patients reported an improved quality of life (QOL) after their operation and the TDAP group showed significantly more improvement than the SSG group. All patients reported a reduction in pain/discomfort but there was no significant difference between groups. CONCLUSION: TDAP flap and SSG both improve QOL for patients with severe axillary HS. The TDAP flap showed greater benefits in terms of QOL, recovery, rate of complications and number of overall procedures.