Pancreatic cancer is a devastating disease with the worst prognosis among all the major human malignancies. The propensity to rapidly metastasize contributes significantly to the highly aggressive feature of pancreatic cancer. The molecular mechanisms underlying this remain elusive, and proteins involved in the control of pancreatic cancer cell motility are not fully characterized. In this study, we find that histone deacetylase 6 (HDAC6), a member of the class II HDAC family, is highly expressed at both protein and mRNA levels in human pancreatic cancer tissues. HDAC6 does not obviously affect pancreatic cancer cell proliferation or cell cycle progression. Instead, it significantly promotes the motility of pancreatic cancer cells. Further studies reveal that HDAC6 interacts with cytoplasmic linker protein 170 (CLIP-170) and that these two proteins function together to stimulate the migration of pancreatic cancer cells. These findings provide mechanistic insight into the progression of pancreatic cancer and suggest HDAC6 as a potential target for the management of this malignancy.
Cell Cycle ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Gene Knockdown Techniques ; Histone Deacetylase 6 ; Histone Deacetylases ; metabolism ; Humans ; Microtubule-Associated Proteins ; metabolism ; Neoplasm Proteins ; metabolism ; Pancreatic Neoplasms ; enzymology ; metabolism ; pathology ; Protein Binding

Angiogenesis, a process by which the preexisting blood vasculature gives rise to new capillary vessels, is associated with a variety of physiologic and pathologic conditions. However, the molecular mechanism underlying this important process remains poorly understood. Here we show that histone deacetylase 6 (HDAC6), a microtubule-associated enzyme critical for cell motility, contributes to angiogenesis by regulating the polarization and migration of vascular endothelial cells. Inhibition of HDAC6 activity impairs the formation of new blood vessels in chick embryos and in angioreactors implanted in mice. The requirement for HDAC6 in angiogenesis is corroborated in vitro by analysis of endothelial tube formation and capillary sprouting. Our data further show that HDAC6 stimulates membrane ruffling at the leading edge to promote cell polarization. In addition, microtubule end binding protein 1 (EB1) is important for HDAC6 to exert its activity towards the migration of endothelial cells and generation of capillary-like structures. These results thus identify HDAC6 as a novel player in the angiogenic process and offer novel insights into the molecular mechanism governing endothelial cell migration and angiogenesis.
Anilides ; pharmacology ; Animals ; Cell Movement ; Cell Polarity ; Cells, Cultured ; Chick Embryo ; Chickens ; Endothelial Cells ; cytology ; Histone Deacetylase 6 ; Histone Deacetylases ; metabolism ; physiology ; Humans ; Hydroxamic Acids ; pharmacology ; Mice ; Microtubule-Associated Proteins ; metabolism ; physiology ; Neovascularization, Physiologic

The traditional view is that breast reconstruction is not an option for day surgery center. As a result, few hospitals in the world conduct this operation in day surgery center. Endoscopic breast reconstruction with liposuction and robot-assisted breast reconstruction are minimally invasive surgeries for breast cancer patients, but they cannot be carried out in the day surgery center due to long operation time. The novel endoscopic-assisted immediate implant-based breast reconstruction after nipple sparing mastectomy through a single axillary incision for breast cancer patients has been successfully conducted in the day surgery center in our hospital due to short operation time and small trauma. Standardized management of the complete process from the patient selection to follow-up after discharge brings rapid recovery and few complications. At the same time, the development of endoscopic surgery makes the breast almost scarless and improves aesthetic results. Therefore, the mode of endoscopic-assisted reconstruction in the day surgery center of our hospital is expected to be popularized in the whole country.

Objective    To explore the surgical technique and preliminary results of endoscopic nipple-sparing mastectomy (E-NSM) and immediate pre-pectoral implant-based breast reconstruction (BR) with titanium-coated polypropylene mesh (TiLoop Bra) via single axillary incision for breast cancer patients. Methods    The clinical data of 9 consecutive female patients who underwent E-NSM and immediate pre-pectoral implant-based BR with TiLoop Bra from  March to May 2021 were retrospectively analyzed. The mean age of patients was 40.6 (22-60) years. The operation time, early complications were collected, and the patients' social and mental health, breast satisfaction and chest function before and after the operation were assessed with the BREAST-Q questionnaire. Results    All the patients had unicentric tumor with a mean diameter of 2.4 (0.6-4.7) cm. The mean distance from the tumor to the nipple was 2.5 (2-4) cm. There were 2 patients with tumor stage 0 and 7 patients with stageⅠ. The mean operation time was 161.1 (125-201) min, the mean blood loss was 41.1 mL and the hospital stay time was 1.5 d. There were 5 patients in the day-care unit. All the patients were successfully followed up with a median follow-up time of 1 (1-2) month. One (11.1%) patient with depigmentation of the nipple-areola complex caused by mild ischemia. None of the patients had incision complications, subcutaneous emphysema, hematoma, infection, nipple-areola or skin flaps necrosis, implant loss. During the follow-up period, no local/regional recurrence or distant metastasis was found. Chest well-being was decreased in the first month after the surgery compared with preoperative status, and the difference was statistically significant (P=0.001). There was no statistical difference in the breast satisfaction or psychosocial function scores between pre- and post-operation (P>0.05). Conclusion    E-NSM and immediate pre-pectoral implant-based BR with TiLoop Bra via single axillary incision has minimal trauma, rapid postoperative recovery, short operation time, few early complications and good early cosmetic effect, and the short-term result is satisfactory.