Fibroblasts induce expression of FGF4 in ovarian cancer stem-like cells/cancer-initiating cells and upregulate their tumor initiation capacity.

Cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) are defined as a small population of cells within cancer that contribute to cancer initiation and progression. Cancer-associated fibroblasts (CAFs) are stromal fibroblasts surrounding tumor cells, and they have important roles in tumor growth and tumor progression. It has been suggested that stromal fibroblasts and CSCs/CICs might mutually cooperate to enhance their growth and tumorigenic capacity. In this study, we investigated the effects of fibroblasts on tumor-initiating capacity and stem-like properties of ovarian CSCs/CICs. CSCs/CICs were isolated from the ovarian carcinoma cell line HTBoA as aldehyde dehydrogenase 1 high (ALDH1(high)) population by the ALDEFLUOR assay. Histological examination of tumor tissues derived from ALDH1(high) cells revealed few fibrous stroma, whereas those derived from fibroblast-mixed ALDH1(high) cells showed abundant fibrous stroma formation. In vivo tumor-initiating capacity and in vitro sphere-forming capacity of ALDH1(high) cells were enhanced in the presence of fibroblasts. Gene expression analysis revealed that fibroblast-mixed ALDH1(high) cells had enhanced expression of fibroblast growth factor 4 (FGF4) as well as stemness-associated genes such as SOX2 and POU5F1. Sphere-forming capacity of ALDH1(high) cells was suppressed by small-interfering RNA (siRNA)-mediated knockdown of FGFR2, the receptor for FGF4 which was expressed preferentially in ALDH1(high) cells. Taken together, the results indicate that interaction of fibroblasts with ovarian CSCs/CICs enhanced tumor-initiating capacity and stem-like properties through autocrine and paracrine FGF4-FGFR2 signaling.

Resveratrol inhibits fibrogenesis and induces apoptosis in keloid fibroblasts.

Keloids are benign dermal fibrotic tumors arising during the wound healing process. The mechanisms of keloid formation and development still remain unknown, and no effective treatment is available. Resveratrol, a dietary compound, has anticancer properties and, from recent studies, it has been suggested that resveratrol may have an antifibrogenic effect on organs such as the liver and kidney. Based on this idea, we investigated its effect on the regulation of extracellular matrix expression, proliferation, and apoptosis of keloid fibroblasts. Type I collagen, α-smooth muscle actin, and heat shock protein 47 expression decreased in resveratrol-treated keloid fibroblasts in a dose-dependent manner. In addition, resveratrol diminished transforming growth factor-ß1 production by keloid fibroblasts. We also demonstrated that it suppressed their proliferation and induced apoptosis of the fibroblasts. Conversely, resveratrol did not decrease type I collagen, α-smooth muscle actin, and heat shock protein 47 mRNA expression in normal skin fibroblasts and barely suppressed cell proliferation. Our data indicate that resveratrol may have an antifibrogenic effect on keloid fibroblasts without any adversely effects on normal skin fibroblasts, suggesting the potential application of resveratrol for the treatment of keloids.

Key amino acid residues involved in the transitions of L- to R-type protofilaments of the Salmonella flagellar filament.

The flagellar filament enables bacteria to swim by functioning as a helical propeller. The filament is a supercoiled assembly of a single protein, flagellin, and is formed by 11 protofilaments arranged in a circle. Bacterial swimming and tumbling correlate with changes of the various helical structures, called polymorphic transformation, that are determined by the ratios of two distinct forms of protofilaments, the L and R types. The polymorphic transformation is caused by transition of the protofilament between L and R types. Elucidation of this transition mechanism has been addressed by comparing the atomic structures of L- and R-type straight filaments or using massive molecular dynamic simulation. Here, we found amino acid residues required for the transition of the protofilament using fliC-intragenic suppressor analysis. We isolated a number of revertants producing supercoiled filaments from mutants with straight filaments and identified the second-site mutations in all of the revertants. The results suggest that Asp107, Gly426, and Ser448 and Ser106, Ala416, Ala427, and Arg431 are the key residues involved in inducing supercoiled filaments from the R- and the L-type straight filaments, respectively. Considering the structures of the R- and L-type protofilaments and the relationship between the rotation of the flagellar motor and the polymorphic transformation, we propose that Gly426, Ala427, and Arg431 contribute to the first stage of the transition and that Ser106, Asp107, and Ala416 play a role in propagating the transitions along the flagellar filament.

Double combined Z-plasty for wide-scar contracture release.

Z-plasty is one of the most widely employed techniques in plastic surgery and mainly serves the following purposes: elongation along the axis of the scar, dispersal of the scar followed by breaking up the straight-line scar and realigning the scar within the lines of minimal tension. It is useful especially to release linear-scar contracture, yet difficult for wide scars. This report describes a novel technique to release contracture effectively for any wide scars using a new design called double combined Z-plasty. The design is simple. The main limb is set to incise the wide scar, and this main limb is shared as a peripheral limb by two other Z-plasty designs. From the main limb, each central limb is designed along the margin of the scar in the opposite direction. The main and central limbs have 90° between them. Other peripheral limbs are then designed facing laterally to the intact skin to make 60° for the central limb. After skin incision, two triangular intact skin flaps could be inserted into the wide scar from both sides, making it possible to release contracture. We performed this technique on eight patients. All wounds healed well and scar contracture was satisfactorily released. This procedure is very useful for wide-scar contracture, compared to conventional Z-plasty.

Clinical and genetic analysis of microtia in Japan.

Microtia is thought to have a multifactorial inheritance, but several investigators disagree. Here we report our survey of the hereditary factors and possible causes. We conducted a questionnaire survey of 428 patients with microtia who were being treated at two hospitals from September 2006 to September 2008. We recorded their age, sex, affected side, duration of gestation, birth weight, age of parents at patients' birth, accompanying malformations, number of siblings, familial occurrence, smoking habit of parents, and medication/disorders of mother during pregnancy, and analysed the results. There were preponderances of male (61%), unilateral (90%) and right-sided disease (59%). Other than the first and second branchial arch syndrome, microtia is often accompanied by other congenital deformities, in particular congenital heart disease; cleft lip, or palate, or both; vertebral defects; and anomalies of extremities. The occurrence in first-degree relatives was 2%. Most maternal disorders and medication taken during pregnancy were common and there was no clear link. Statistically, there was a tendency to low birth weight and high maternal age, but it is not possible to identify these as a specific cause of microtia. Multifactorial inheritance is unlikely to be the cause of microtia as there was only one finding in agreement with its widely accepted characteristics. However, we cannot completely discount it as there were too few cases in some groups to make a judgement.

Combined revascularization and free-tissue transfer for limb salvage in a Buerger disease patient.

Buerger disease is a limb-threatening condition occurring in young smokers, and its treatment has been a challenging problem, although a large number of medical and surgical options have been suggested. Combined surgery for revascularization and free-tissue transfer for Buerger disease is an aggressive and attractive option. This complex surgery enables successful treatment of tissue loss caused by ischemia. We performed revascularization and free-tissue transfer to the critically ischemic limb in a patient with Buerger disease. In this case, the procedure is attempted to salvage a limb from amputation.

The reverse superficial temporal artery flap from the preauricular region, for the small facial defects.

BACKGROUND: For the reconstruction of facial defects, the retroauricular flap is generally used. However, this flap has disadvantages, such as venous return disturbance and reddish skin colour peculiar to the retroauricular region. METHODS: Here, we report the reverse superficial temporal artery (STA) flap, elevated from the preauricular region. In our method, the flap is retrogradely elevated including the STA under the skin island in the preauricular region and the temporoparietal fascia around the superficial temporal vessels in the temporal region. The donor site is closed primarily or by the retroauricular flap. RESULTS: Five cases with a pedicled flap and one case with a free flap were treated using our method. In one case, a minor congestion of the flap occurred postoperatively, and temporary facial nerve palsy in another case. In all cases, the results were cosmetically good, and the scar at the donor site was inconspicuous. CONCLUSIONS: As compared to the retroauricular flap, our method is easier to perform and the flap has a reliable blood circulation. Moreover, it can be used with both a pedicled and a free flap, leaving an inconspicuous scar at the donor site, and a colour match without reddish skin. Therefore, when considering reconstruction of small-sized defects on the face, our method is more useful than the retroauricular flap.

The usefulness of the collagen and elastin sponge derived from salmon as an artificial dermis and scaffold for tissue engineering.

Collagen sponge is one of the medical materials that are frequently used in clinical medicine. However, the problem of prion disease harmfully affected the usage of mammals-derived medical materials. Since there have been no reports about prion disease occurring in marine products, we produced the collagen and elastin sponge (CES) made from salmon, and investigated whether the CES could be a substitute for mammalian collagen sponge. Fibroblasts were seeded in the CES to examine whether the CES could be used as a scaffold for tissue engineering. The results of the WST-1 assay showed that the fibroblasts were viable and were well proliferated in the CES. To examine whether the CES could be used as an artificial dermis, the CES and TERUDERMIS (traditional collagen sponge) were grafted onto the skin defects on the dorsum of rats. The histological findings of these ulcers showed non-significant difference between the CES and TERUDERMIS. Because of the safety, the abundance of the resources, and the possessing same ability as TERUDERMIS, the biomedical materials derived from marine products may be a substitute for those derived from mammals.

Three cases of giant pilomatrixoma--considerations for diagnosis and treatment of giant skin tumours with abundant inner calcification present on the upper body.

BACKGROUND: Pilomatrixoma frequently occurs as a solitary, small tumour on the face or upper extremities of people younger than 20 years. METHODS: We report three cases of giant pilomatrixoma. In all these cases, outward appearances and imaging investigations suggested malignant tumours. Preoperative biopsies suggested that case 1 was a basal cell carcinoma, but cases 2 and 3 had no malignant features on biopsy. Two of the cases experienced rare complications - hypercalcaemia caused by parathyroid-related protein (PTHrP) production and multiple occurrences. RESULTS: All three tumours were removed with a 1-3-cm margin. The postoperative histopathologies showed pilomatrixoma in all three cases. CONCLUSIONS: Rarely, pilomatrixoma develops to a giant size with various atypical outward appearances consistent with a malignant tumour. Preoperative clinical appearances frequently lead to misdiagnosis, and preoperative examinations are unreliable. Therefore, when a giant tumour with abundant inner calcification is present in a young patient, the possibility of a pilomatrixoma should be considered.

Reverse facial artery flap from the submental region.

BACKGROUND: Of all the local flaps that allow elevation of a sufficiently large-sized flap while also leaving an inconspicuous donor-site scar, the submental island flap is frequently used for the reconstruction of a defect in the lower two-thirds of the face. However, this flap has certain disadvantages such as the technique being slightly difficult to perform and, more importantly, that it carries a significant risk of injury to the facial nerve. METHODS: Here, we propose the reverse facial artery flap, elevated from the submandibular region. Our method creates a flap that includes only the platysma under the skin island, without either the submental or facial artery. However, above the superior border of the skin island, the flap includes the facial artery along with subcutaneous soft tissue. The blood circulation of the skin island is in a random pattern and that of the subcutaneous pedicle is in an axial pattern. RESULTS: Four cases were treated using our method. There were no complications in all four cases, and the results were also cosmetically very good. CONCLUSIONS: As compared to the submental island flap, our method is easier to perform and carries a much lower risk of damage to the marginal mandibular branch of the facial nerve, as the facial artery crosses over the facial nerve at only one point. In addition, the method produces a thin flap. Therefore, when considering correction of a small-sized defect in the lower two-thirds of the face, our method has a number of advantages over the submental island flap.

Reconstruction of a red lip that has a defect in one half, using the remaining red lip.

It is difficult to reconstruct the red lip and achieve good functional results such as normal sphincter force, sensitivity and movement of the lip. In addition, it is also difficult to attain colour and texture matches. We reconstruct a red lip that has a defect in one half, using the remaining red lip. Using the technique reported herein, we can achieve excellent functional and aesthetic results. Functionally, sphincter force and sensation recover early and the movement of the lip returns to normal. In addition, the reconstructed lip develops a symmetrical and natural appearance.

The acute surgical management of injury to the helix and antihelix in patients with large body surface area burns.

Deformity or loss of the ear may be caused by superficial dermal burns or deep burns. The depth of ear burns is progressive because the ear protrudes from head and is easily affected by external pressure. Therefore, burn wounds of the ear should be debrided as early as possible, before irreversible changes of the cartilage, and covered with healthy tissue. We describe a surgical procedure for treatment of the extensively burned ear. With this technique, the helix is covered by a postauricular advancement flap, and the antihelix is covered by a skin graft. Because the procedure is straightforward and can be completed within a short time, it can be performed at the same time as other life-saving measures. The use of a skin flap permits adequate debridement in terms of both depth and width, minimising the risk of infection. The helix can be reconstructed to provide a natural appearance, and late ulcer formation due to external irritation is prevented. We have treated 15 ears on 11 patients with this procedure and have consistently obtained a satisfactory outcome.

A circumferential incision technique to release wide scar contracture.

SUMMARY: Wide scar contracture in patients with large burns is generally treated with a skin graft or flap after release of the contracture. In children, however, the creation of a new scar at the donor site should be avoided because additional operations are sometimes required later in life. Patients with large scars often lack adequate donor sites. We describe a simple technique that effectively reduces wide scar contracture without the use of a skin graft or flap. A spindle-shaped incision line is designed around the contracted scar. The major axis of the spindle should coincide with the direction of strongest contracture. Incision of the skin releases the contracture, and the surrounding skin returns to a normal position. If satisfactory release of the contracture is not obtained by a simple incision, the surrounding skin is slightly undermined. The doughnut-like skin defect resulting from undermining is sutured again, taking care to avoid increased tension in the direction of contracture. We used this technique to treat 28 scar contractures in 21 patients. All sites had good outcomes without any complications, such as congestion or haematoma. Scar contracture markedly resolved, both subjectively as well as objectively. Hard red scars consistently became whiter and softer after the operation. The design is similar to the double opposing V-Y plasty or rhomboid flap but the significant feature of our technique is that the design includes the entire scar in the central area. It makes it possible to release multiple contracture bundles or a largely contracted area at one time. This technique is simple, safe, minimally invasive for patients, and requires no other donor sites. It should be tried before resorting to the use of skin grafts or flaps in patients with large scar contractures.