Prognostic Value of Intratumoral Collagen Quantification in Canine Oral Melanomas

The majority of the melanocytic neoplasms are considered malignant and highly metastatic. However, a subset of the melanocytic tumors has a more favorable prognosis and the identification of precise prognostic markers for this neoplasm may be useful to guide treatment. The collagen architecture and density have been shown to correlate with tumor progression in human breast cancer and canine mast cell tumors. The purpose of the present study was to investigate the prognostic value of the intratumoral collagen index (ICI) as an indicator of postsurgical survival and its relation with other prognostic markers for canine oral melanomas (OMs). Twenty-two cases were tested for intratumoral collagen density using Masson's trichrome stain and morphometry. No differences were found between dogs regarding survival. The ICI was not correlated with proliferative activity or nuclear atypia. The results presented herein indicate that the quantity of intratumoral collagen in canine OMs is not an efficient indicator of postsurgical survival. Complementary studies about the expression and activity of enzymes that are capable of degrading extracellular matrix (ECM) components are necessary.

Solitary skin-colored nodule on a child’s face

Sir, A healthy, six-year-old boy presented with a slowly grown dome-shaped nodule on the mandibular angle region present for two years. The patient’s past medical and family history were unremarkable. A physical examination revealed a solitary, 1.3 × 1 cm, firm, painless, flesh-colored tumor (Fig. 1). Dermoscopy showed branching, serpentine vessels on a pink background (Fig. 2a). These features disappeared when slight pressure was exerted on the dermoscope and the tumor exhibited a central, white, structureless area (Fig. 2b). An excisional biopsy was performed. A microscopic examination showed a well-circumscribed, paucicellular dermal tumor composed of eosinophilic collagen bundles separated by clefts and forming a storiform pattern. Scattered fibroblasts were found among the collagen bundles. The overlying epidermis was slightly flattened (Fig. 3). The diagnosis of solitary sclerotic fibroma was established. Sclerotic fibroma (SF), also known as storiform collagenoma, is a rare benign skin tumor. It usually manifests itself as an asymptomatic, slowly growing, white-to-skin-colored papule or nodule [1]. It was first described in patients with Cowden’s disease, yet may also occur sporadically [2]. There were no mucocutaneous features of Cowden’s disease (tricholemmomas, oral fibromas, acral keratoses, palmar pits, and gingival and palatal papules) in the patient and her family members. Dermatofibroma, the main differential diagnosis of SF, usually exhibits hyperplastic changes of the epidermis instead of atrophy, and the boundaries of the lesion are unclear [2]. Only two papers have been published describing the dermoscopic findings of SF, consisting of a white background with peripheral arborizing vessels [3]. A white background may be related to an increased dermal collagen density. It is also described in dermatofibroma, typically with a peripheral pigmentation network. Although dermoscopy may improve the clinical diagnosis of SF, histopathological analysis is required.

The Superior Outcome of Collagen Nanosilver in Increasing Macrophage and Collagen on Deep Dermal Burn Wound Healing

AIM: This study aims to prove the superior outcome of collagen nanosilver in increasing macrophage and collagen on deep dermal burn wound healing. METHODS: This study was a randomized control trial design. All animals used were male Sprague Dawley rats aged 12–14 weeks old and weighed about 200–250 g. Each rat gets four site injuries and is given treatments. The treatment group includes: I (negative control using NaCl 0.9%), II (positive control using silver sulfadiazine cream), III (treatment with nanosilver collagen cream 1%), and IV (treatment with collagen nanosilver cream 2%). Macrophages counts were assessed using IHC F40/80 and collagen density was assessed using Masson’s trichrome staining. RESULTS: Macrophage on day 6 showed a significant difference as seen in group III and group IV. A significant difference was also obtained between macrophage on day 3 and day 6 from group IV, likewise between collagen between day 3 and day 6 from group III and IV. Collagen nanosilver acts as an antimicrobial and anti-inflammatory agent by increasing the mechanism of activation and migration of macrophages to the site of injury. Moreover, this formula modulated the collagen deposition, which forms the tissue fibers which ultimately provide a conducive environment for wound healing. CONCLUSION: Collagen nanosilver has a superior outcome in the increasing macrophage cell count and collagen density of deep dermal burn wound healing.

Effect of Blue-Light-Emitting Diode Exposure on Collagen Density of Periodontal Ligament During Orthodontic Tooth Movement in Rats

Photobiomodulation therapy using Light Emitting Diode (LED) with a certain period and intensity can stimulate tissue repair and accelerate orthodontic tooth movement. During remodeling, collagen on periodontal ligaments was formed on the pressure and tension sides. The aim of this study was to investigate the effect of exposure time and observation day of blue LED on the collagen density of periodontal ligament of the pressure and tension sides of Wistar rats. Forty-eight male Wistar rats aged 3-4 months weighing 300-500 grams were divided into four groups: the control group; the group exposed to LED with λ1000 nm of 490 mW/cm2 for 25, 30, and 35 seconds once a day. In addition, their mandibular inter-incisor was administered with thirty-five grams orthodontic force using an open coil spring. The calculations on the collagen density of pressure and tension sides were carried out on days 0, 3, 7, and 14 using the TinEye application. Statistical analysis test was conducted using two-way ANOVA and LSD post hoc test. The results showed a more significant increase in the collagen density of the pressure and tension sides than that of the control group (p <0.05). The collagen density of pressure and tension sides reach the highest point at 30 seconds exposure followed by 35 and 25 seconds. The collagen density of pressure sides decreased on the 3rd day and increased afterward, and the tension sides continued to increase on the 3rd day afterward. The study showed that blue light LEDs were able to increase collagen density on the pressure and tension sides, with optimal exposure at 30 seconds, and it reached the highest point at day 14.

Immune Modulatory Properties of Collagen in Cancer

During tumor growth the extracellular matrix (ECM) undergoes dramatic remodeling. The normal ECM is degraded and substituted with a tumor-specific ECM, which is often of higher collagen density and increased stiffness. The structure and collagen density of the tumor-specific ECM has been associated with poor prognosis in several types of cancer. However, the reason for this association is still largely unknown. Collagen can promote cancer cell growth and migration, but recent studies have shown that collagens can also affect the function and phenotype of various types of tumor-infiltrating immune cells such as tumor-associated macrophages (TAMs) and T cells. This suggests that tumor-associated collagen could have important immune modulatory functions within the tumor microenvironment, affecting cancer progression as well as the efficacy of cancer immunotherapy. The effects of tumor-associated collagen on immune cells could help explain why a high collagen density in tumors is often correlated with a poor prognosis. Knowledge about immune modulatory functions of collagen could potentially identify targets for improving current cancer therapies or for development of new treatments. In this review, the current knowledge about the ability of collagen to influence T cell activity will be summarized. This includes direct interactions with T cells as well as induction of immune suppressive activity in other immune cells such as macrophages. Additionally, the potential effects of collagen on the efficacy of cancer immunotherapy will be discussed.

THE COMPARISON OF RAMANIA (Bouea macrophylla Griff) AND BINJAI (Mangifera caesia) LEAVES EXTRACT GEL EFFECT ON COLLAGEN DENSITY

Background: The extract of ramania Bouea macrophylla Griff) and binjai (Mangifera caesia) leaf have flavonoid compounds that function as antioxidants to balance the amount of Reactive Oxygen Species (ROS) in tissues and optimize wound healing by helping synthesis of hydroxyproline which is used as a collagen synthesis material. Objective: To compare the effect of 15% concentration of ramania leaf extract gel, 15% concentration of binjai leaf extract gel on collagen density in back incision wounds of male Wistar rats on day 7 and day 14. Methods: This study used a true experimental design with a posttest-only with control group design. The study sample used male wistar rats that were healthy and active, aged 2-3 months with a body weight of 250-300 grams. The total sample was 18 rats divided into 6 groups. The 15% concentration of ramania and binjai leaves was given topically, then the rats were euthanized on the 7th and 14th day. Collagen index measurement was using hydroxyproline concentration. Results: Two-way Anova data analysis showed a significant value of 0.00 (p<0.05), which means that there was a difference in effect between the treatment gel and wound day. Bonferroni Post Hoc test showed a significant value in all treatment gel groups. Conclusion: There is a difference in the effect of 15% concentration of ramania leaf extract gel and 15% concentration of binjai extract gel on collagen density. Binjai leaf extract gel at 15% concentration is more effective for collagen density than Ramania leaf extract at 15% concentration and placebo. Keywords : Binjai Leaf Extract Gel, Collagen, Hydroxyproline, Ramania Leaf Extract Gel.

Matrix Metalloproteinase-9 is Involved in the Fibrotic Process in Denervated Muscles after Sciatic Nerve Trauma and Recovery

Fibrosis of the injured muscles is a problem of recovery from trauma and denervation. The aim of the work was to investigate the interconnection of matrix metalloproteinase-9 (ММР-9) activity in denervated muscles with fibrosis and to estimate its role in nerve restoration by the epineurial suture, fibrin-based glue, and polyethylene glycol hydrogel. The activity of matrix metalloproteinases was estimated by gelatin zymography. Collagen density in muscles was determined histochemically. An increased level of the active MMP-9 is associated with the fibrous changes in the denervated skeletal muscles and after an epineurial suture. The use of fibrin glue and polyethylene glycol hydrogel resulted in a lower level of collagen and ММР-9 activity, which may be a therapeutic target in the treatment of neuromuscular lesions, and has value in fibrosis analysis following microsurgical intervention for peripheral nerve reconstruction.

The Bladder Is a Novel Target of Developmental Polychlorinated Biphenyl Exposure Linked to Increased Inflammatory Cells in the Bladder of Young Mice

Bladder inflammation is associated with several lower urinary tract symptoms that greatly reduce quality of life, yet contributing factors are not completely understood. Environmental chemicals are plausible mediators of inflammatory reactions within the bladder. Here, we examine whether developmental exposure to polychlorinated biphenyls (PCBs) leads to changes in immune cells within the bladder of young mice. Female mice were exposed to an environmentally relevant mixture of PCBs through gestation and lactation, and bladders were collected from offspring at postnatal day (P) 28–31. We identify several dose- and sex-dependent PCB effects in the bladder. The lowest concentration of PCB (0.1 mg/kg/d) increased CD45+ hematolymphoid immune cells in both sexes. While PCBs had no effect on CD79b+ B cells or CD3+ T cells, PCBs (0.1 mg/kg/d) did increase F4/80+ macrophages particularly in female bladder. Collagen density was also examined to determine whether inflammatory events coincide with changes in the stromal extracellular matrix. PCBs (0.1 mg/kg/d) decreased collagen density in female bladder compared to control. PCBs also increased the number of cells undergoing cell division predominantly in male bladder. These results implicate perturbations to the immune system in relation to PCB effects on the bladder. Future study to define the underlying mechanisms could help understand how environmental factors can be risk factors for lower urinary tract symptoms.