Alteration of Pituitary Tumor Transforming Gene 1 by MicroRNA-186 and 655 Regulates Invasion Ability of Human Oral Squamous Cell Carcinoma.

BACKGROUND: Pituitary tumor-transforming gene 1 (PTTG1) was recently shown to be involved in the progression as well as the metastasis of cancers. However, their expression and function in the invasion of oral squamous cell carcinoma (SCC) remain unclear. METHODS: The expressions of PTTG1 and PTTG1-targeted miRNA in oral SCC cell lines and their invasion capability depended on PTTG1 expression were analyzed by quantitative RT-PCR, Western blots, the transwell insert system and Zymography. RESULTS: Invasion abilities were decreased in oral SCC cells treated with siRNA-PTTG1. When PTTG1 were downregulated in oral SCC cells treated with microRNA-186 and -655 inhibited their invasion abilities via MMP-9 activity. CONCLUSIONS: These results indicate that alteration of expression of PTTG1 in oral SCC cells by newly identified microRNA-186 and -655 can regulate invasion activity. Therefore, these data offer new insights into further understanding PTTG1 function in oral SCC and should provide new strategies for diagnostic markers for oral SCC.

Effects of 4-Hexylresorcinol on Craniofacial Growth in Rats.

4-Hexylresorcinol (4HR) has been used as a food additive, however, it has been recently demonstrated as a Class I histone deacetylase inhibitor (HDACi). Unlike other HDACi, 4HR can be taken through foods. Unfortunately, some HDACi have an influence on craniofacial growth, therefore, the purpose of this study was to evaluate the effects of 4HR on craniofacial growth. Saos-2 cells (osteoblast-like cells) were used for the evaluation of HDACi and its associated activities after 4HR administration. For the evaluation of craniofacial growth, 12.8 mg/kg of 4HR was administered weekly to 4 week old rats (male: 10, female: 10) for 12 weeks. Ten rats were used for untreated control (males: 5, females: 5). Body weight was recorded every week. Serum and head samples were collected at 12 weeks after initial administration. Craniofacial growth was evaluated by micro-computerized tomography. Serum was used for ELISA (testosterone and estrogen) and immunoprecipitation high-performance liquid chromatography (IP-HPLC). The administration of 4HR (1-100 µM) showed significant HDACi activity (p < 0.05). Body weight was significantly different in male rats (p < 0.05), and mandibular size was significantly smaller in 4HR-treated male rats with reduced testosterone levels. However, the mandibular size was significantly higher in 4HR treated female rats with increased growth hormone levels. In conclusion, 4HR had HDACi activity in Saos-2 cells. The administration of 4HR on growing rats showed different responses in body weight and mandibular size between sexes.

The Administration of 4-Hexylresorcinol Accelerates Orthodontic Tooth Movement and Increases the Expression Level of Bone Turnover Markers in Ovariectomized Rats.

Surgical methods for accelerating orthodontic tooth movement are limited by possible damage to the tooth root and patient discomfort. 4-Hexylresorcinol (4HR) has been shown to increase bone remodeling and may potentially facilitate tooth movement. This study investigated the (1) effect of 4HR administration on osteoblast-like cells and (2) effect of 4HR administration on tooth movement in ovariectomized rats. Saos-2 cells were treated with either 4HR or solvent (control). Protein expression levels were investigated 2, 8, and 24 h after treatment. Thirty ovariectomized Sprague-Dawley rats were divided into two experimental groups (A and B) and one control group. After installation of an orthodontic tooth movement device, groups A and B received subcutaneous weekly injections of 4HR (1.28 and 128 mg/kg). Micro-computerized tomography and histological analyses were performed after 2 weeks of tooth movement. The application of 4HR elevated expression of osteogenic markers in Saos-2 cells. Movement of the first molars was significantly greater in rats administered 4HR. Furthermore, the expression of bone morphogenic protein-2, receptor activator of nuclear factor kappa-B ligand, osteocalcin, and tartrate-resistant acid phosphatase were increased after 4HR administration. 4HR application demonstrated increased expression of osteogenic markers in Saos-2 cells and accelerated orthodontic tooth movement in rats.

Clinical classification of cervical necrotizing fasciitis.

PURPOSE: Necrotizing fasciitis of the craniofacial region is a rare and potentially life-threatening bacterial infectious disease. Odontogenic infections primarily spread along facial fascia and subcutaneous tissues, resulting in upper chest skin or thoracic necrosis. The purpose of this clinical classification was to demonstrate clinically important guidelines for early diagnosis and prompt management of CNF. METHODS: Although the incidence of cervical necrotizing fasciitis (CNF) is very rare in many developed countries, prompt management with appropriate initial diagnosis is essential, especially in tropical low-economic rural regions of African countries. Over the last 12 years, our charitable team in West Africa made clinical classifications of CNF according to onset time and spreading pattern to thoracic extension. RESULTS: CNF patients could be divided into two primary types, limited to neck type and extended to upper chest type. We also further categorized from each type into three different groups according to the CNF onset and clinical characteristics, including acute type with hematogenous spread within 2 weeks, subacute type with suppuration over 2 to 4 weeks, chronic type without suppuration over 4 weeks, multiple type with partial skin necrosis, island type with necrotic skin coverage, and broad type with whole skin necrosis. CONCLUSIONS: These classifications will help decrease the mortality rate in severely infected patients.

Identification of human papillomavirus (HPV) subtype in oral cancer patients through microarray technology.

PURPOSE: Human papilloma virus (HPV) is the main source of cervical cancer. Many recent studies have revealed the prevalence and prognosis of HPV associated with oropharyngeal squamous cell carcinoma, but fewer reports have evaluated HPV in oral squamous cell carcinoma (OSCC). The purpose of this study was to determine the prevalence and prognosis of HPV associated with OSCC according to HPV and tumor types. MATERIALS AND METHODS: We used a DNA chip kit (MY-HPV chip kit ®, Mygene Co., Korea) to detect high-risk HPV subtypes (16, 18, 31, 33, 35, 39, 45, 51, 52, 54, 56, 58) and low-risk subtypes (6, 11, 34, 40, 42, 43, 44) among 187 patients. The prevalence was determined by Chi-square and Fisher's exact tests, and the prognosis was calculated by the Kaplan-Meier method and the log-rank test. RESULTS: The overall prevalence of HPV in OSCC was 7.0% for all HPV positives and 4.3% for high-risk HPV positives. The prevalence of HPV was significantly higher in individuals under 65 years old and in those with tumors in the tongue and gum regions. The prognosis did not differ between the HPV-positive and -negative groups. Although the prevalence of HPV-positive cases in OSCC was low (7.0, 4.3%) and the prognosis did not depend on HPV positivity, HPV-associated OSCC should be considered in the evaluation and treatment of oral cancer patients. In addition, separating high- and low-risk groups based on the HPV status of other body parts might not be appropriate. DISCUSSION: The DNA microarray method can accurately detect known HPV subtypes simultaneously, but has limitations in detecting new subtypes. Vaccines can also be used to prevent HPV-associated OSCC in patients, so further studies on the prognosis and efficacy of vaccines should be undertaken.

Silicone Facial Prosthesis: A Preliminary Report on Silicone Adhesion to Magnet.

Although a silicone facial prosthesis has many advantages, silicone's limited cementation with resin or metal has caused many maxillofacial reconstructive surgeons and prosthodontists concern regarding the use of silicone-based facial prostheses. This study demonstrates 1 representative silicone facial prosthesis patient with magnet cementation to silicone using plastic clay, which will be applied to various maxillofacial prosthesis strategies in the near future.

Autogenous Partial Bone Chip Grafting on the Exposed Inferior Alveolar Nerve After Cystic Enucleation.

This prospective study evaluated the clinical effectiveness of the new approach of partial autogenous bone chip grafts for the treatment of mandibular cystic lesions related to the inferior alveolar nerve (IAN). A total of 38 patients treated for mandibular cysts or benign tumors were included in this prospective study and subsequently divided into 3 groups depending on the bone grafting method used: cystic enucleation without a bone graft (group 1), partial bone chip graft covering the exposed IAN (group 2), and autogenous bone graft covering the entire defect (group 3). We evaluated the symptoms, clinical signs, and radiographic changes using dental panorama preoperatively, immediate postoperatively, and at 1, 3, 6, and 12 months postoperatively. Radiographic densities were compared using Adobe Photoshop CS5 (Adobe Systems Inc., San Jose, CA). Repeated measures analysis of variance was used for statistical evaluation with SPSS 22.0 (SPSS Inc, Chicago, IL), and P < 0.05 was considered statistically significant.Radiopacities were the most increased at 1 year postoperative in group 3; groups 2 and 3 did not show statistically significant differences, whereas groups 1 and 3 were statistically significant. In terms of radiographic bone healing with clinical regeneration of the exposed IAN, healing occurred in all patients, although the best healing was achieved in group 2.This autogenous partial bone chip grafting procedure to cover the exposed IAN is suggested as a new surgical protocol for the treatment of cystic lesions associated with the IAN.

Two different protein expression profiles of oral squamous cell carcinoma analyzed by immunoprecipitation high-performance liquid chromatography.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is one of the most dangerous cancers in the body, producing serious complications with individual behaviors. Many different pathogenetic factors are involved in the carcinogenesis of OSCC. Cancer cells derived from oral keratinocytes can produce different carcinogenic signaling pathways through differences in protein expression, but their protein expression profiles cannot be easily explored with ordinary detection methods. METHODS: The present study compared the protein expression profiles between two different types of OSCCs, which were analyzed through immunoprecipitation high-performance liquid chromatography (IP-HPLC). RESULTS: Two types of squamous cell carcinoma (SCC) occurred in a mandibular (SCC-1) and maxillary gingiva (SCC-2), but their clinical features and progression were quite different from each other. SCC-1 showed a large gingival ulceration with severe halitosis and extensive bony destruction, while SCC-2 showed a relatively small papillary gingival swelling but rapidly grew to form a large submucosal mass, followed by early cervical lymph node metastasis. In the histological observation, SCC-1 was relatively well differentiated with a severe inflammatory reaction, while SCC-2 showed severely infiltrative growth of each cancer islets accompanied with a mild inflammatory reaction. IP-HPLC analysis revealed contrary protein expression profiles analyzed by 72 different oncogenic proteins. SCC-1 showed more cellular apoptosis and invasive growth than SCC-2 through increased expression of caspases, MMPs, p53 signaling, FAS signaling, TGF-ß1 signaling, and angiogenesis factors, while SCC-2 showed more cellular growth and survival than SCC-1 through the increased expression of proliferating factors, RAS signaling, eIF5A signaling, WNT signaling, and survivin. CONCLUSIONS: The increased trends of cellular apoptosis and invasiveness in the protein expression profiles of SCC-1 were implicative of its extensive gingival ulceration and bony destruction, while the increased trends of cellular proliferation and survival in the protein profile of SCC-2 were implicative of its rapid growing tumor mass and early lymph node metastasis. These analyses of the essential oncogenic protein expression profiles in OSCC provide important information for genetic counseling or customized gene therapy in cancer treatment. Therefore, protein expression profile analysis through IP-HPLC is helpful not only for the molecular genetic diagnosis of cancer but also in identifying target molecules for customized gene therapy in near future.

Wound healing protein profiles in the postoperative exudate of bisphosphonate-related osteonecrosis of mandible.

Recurrent bacterial infections in cases of bisphosphonate-related osteonecrosis of jaw (BRONJ) frequently occur. Therefore, BRONJ are usually treated by radical saucerization followed by intensive antibiotic medications without bisphosphonate therapy. The postoperative exudate (POE) from BRONJ lesions may directly indicate the inflammatory status of osteomyelitis in patients, but so far, the POE has rarely been examined for its expression of various cytokines and wound healing proteins. A total of 27 cases of BRONJ, which involved the mandible, were selected and their individual POE collected 6 h, 1 day, and 2 days after surgical intervention was analyzed by immunoprecipitation high performance liquid chromatography (IP-HPLC). The different protein expressions in the BRONJ POE were compared with findings from ten cases of chronic mandibular osteomyelitis (CMO) exudate as the control group. For the protein expressions for inflammation, osteogenesis, and angiogenesis, in the 6 h POE sample, the BRONJ exudate exhibited more expression of IL-10, IL-28, OPG, and osteocalcin, but less expression of TNFα and LL-37 than the control. In the 1 day POE sample, the BRONJ exudate showed more expression of TNFα, IL-6, 8, 12, 28, α1-antitrypsin, VEGF-A, and VEGF-C, but less expression of CD68, lysozyme, bFGF, RANKL, bFGF, and ALP than the control. In the 2 day POE sample, the BRONJ exudate consistently showed more expression of LL-37, ß-defensin-1, and VEGF-A than the control. The present BRONJ POE revealed the rapid progress of bony wound healing through increased molecular signaling for inflammation, angiogenesis, and osteogenesis compared to the control. Therefore, it was suggested that the POE obtained from the postoperative bony lesions should be collected and analyzed by the IP-HPLC method to predict the prognosis of seriously complicated inflammatory bony diseases such as BRONJ.

Differential protein expression in the secretory fluids of maxillary sinusitis and maxillary retention cyst.

Both maxillary sinusitis (MS) and maxillary retention cyst (MRC) involve the maxillary sinus and show similar clinical features. Clinically, differentiating between MS and MRC is sometimes difficult in asymptomatic patients, despite their quite different pathogenic behaviors. To identify differential protein expressions in the secretory fluids of MS and MRC, 25 cases of asymptomatic MS and 15 cases of asymptomatic MRC were examined pathologically in this study. All patients underwent routine endoscopic sinus surgery or modified Caldwell-Luc procedure and the sinus mucosal specimens obtained during these procedures with the approval of the Institutional Review Board. Their secretory fluids were analyzed via immunoprecipitation-based high-performance liquid chromatography (IP-HPLC) using 25 types of antiserum, including inflammatory cytokines, antimicrobial proteins, and mucosal protective proteins. In the histological examinations, MS and MRC showed similar features in the secretory columnar epithelial lining and thick submucosal connective tissue, both of which contained few inflammatory cells infiltrates. The IP-HPLC analysis revealed that TNFα, IL-1, -8, MMP-3, -10, α1-antitrypsin, cathepsin C, lysozyme, lactoferrin, ß-defensin-1, -3, LL-37, mucocidin, and mucin-1 were more intensely expressed in MS than in MRC; whereas IgA, cystatin A, and proline-rich proteins were more strongly expressed in MRC than in MS. These data indicate that the secretory fluid of MS is indicative of a more robust inflammatory reaction to certain bacteria compared to that of MRC, while the secretory fluid of MRC contains more abundant mucosal protective proteins compared to that of MS. Taken together, the IP-HPLC analysis of MS and MRC secretory fluid revealed that MRC showed a weaker inflammatory reaction but a stronger mucosal protective function than MS.

Pediatric Glial Heterotopia in the Medial Canthus.

Glial heterotopias are rare, benign, congenital, midline, and nonteratomatous extracranial glial tissue. They may be confused as encephalocele or dermoid cysts and are mostly present in the nose.An 8-month-old African female child presented with a slow growing paranasal mass. The mass had been present at the left upper medial canthus since birth and had slowly and progressively enlarged. There was no communication between the mass and the cranial cavity during the operational procedure. The mass was immunohistochemically positive for S-100 protein as well as for glial fibrillary acidic protein, but negative for proliferating cell nuclear antigen. This suggested that the mass was composed of benign glial tissues with many astrocytes.The purpose of this report is to demonstrate the first patient with pediatric glial heterotopic tissue in the medial canthus and to report the clinical importance of its immunohistochemical findings.

Clinical Manifestation of a Patient With Forehead Sparganosis.

Human sparganosis is a parasite infection caused by the larva of a tapeworm of the genus Spirometra. Ocular, central nervous system, auricular, pulmonary, intraosseous, intraperitoneal, and subcutaneous manifestations of this infection in the neck or inguinal region have been described.The authors report the rare occurrence of cutaneous forehead sparganosis of a 19-year-old male who presented with a soft subcutaneous mass in the forehead, along with a related literature review.

Bizarre parosteal osteochondromatous proliferation in the lingual area of the mandibular body versus osteochondroma at the mandibular condyle.

BACKGROUND: Bizarre parosteal osteochondromatous proliferation (BPOP) is benign and usually occurs in the small tubular bones of the hands and feet, but it is extremely rare in the oral and maxillofacial region. METHODS: The present study compares a case of BPOP occurring in the lingual area of the right mandibular body with a representative case of osteochondroma occurring in the left mandibular condyle using immunohistochemical methods. RESULTS: BPOP showed no continuity to the cortical bone of the mandible on X-ray and was histologically composed of immature cartilage and bone tissues, whereas osteochondroma showed overgrowth of hypertrophic chondrocytes accompanied by mature bone with endochondral ossification. Although BPOP showed no features of cellular atypia or malignant transformation, it expressed more osteogenic proteins, including BMP-2, BMP-4, RUNX2, OC, AP, OPG, RANKL, CTGF, and bFGF, than osteochondroma. Furthermore, the perichondral spindle cells and marrow osteoblasts/fibroblasts of BPOP showed stronger immunoreaction of PCNA, p53, ß-catenin, BCL2, pAKT, survivin, 14-3-3, CEA, EMA, pan-K, and S-100 than the tumor cells of osteochondroma. CONCLUSIONS: Therefore, it was presumed that similar to embryonal osteochondroid tissue, BPOP might be activated by osteogenic and oncogenic signaling and that this increased signaling may explain the rapid growth and high recurrence of BPOP.

Pathologic mandibular fracture after biting crab shells following ramal bone graft.

The mandibular ramus is considered an appropriate choice for reconstruction of maxillofacial defects because of sufficient amounts of material and fewer donor site complications. Although bone harvesting from the mandibular ramus has many advantages, in rare cases it can result in pathologic fracture of the mandible. Here, we present a case of 59-year-old man who suffered a pathologic mandible fracture related to biting hard foods, such as crab shells, after a sinus bone lifting with ramal bone graft procedure performed 2 weeks prior. He underwent closed reduction by intermaxillary fixation with an arch bar over the course of 4 weeks. Three months later, the patients had a stable occlusion with normal mouth opening and sensation. To prevent this complication, the osteotomy should be performed in such a way that it is not too vertical during ramal bone harvesting. Furthermore, we wish to emphasize the importance of patients being instructed to avoid chewing hard foods for at least 4 weeks after ramal bone harvesting.

Mandibular clear cell odontogenic carcinoma.

BACKGROUND: Clear cell odontogenic carcinoma (CCOC) is a rare intraosseous carcinoma of the jaw; only 81 cases have been reported in the English literatures. CASE PRESENTATION: We reported an additional case and reviewed the existing literature. A 70-year-old woman presented with a large painful radiolucent mandibular lesion from the right canine to the left angle area through the midline. No metastatic lymph nodes or distant metastases were detected. She underwent wide surgical resection and reconstruction with a composite fibula free flap. She had no recurrence or metastasis after 18 months. CONCLUSION: CCOC occurs predominantly in women in their 50s-70s in the mandible. Painless swelling is the most common symptom, followed by pain, teeth loosening, and paresthesia. CCOC has a good prognosis after surgery. In large mandibular CCOC, wide resection and composite fibula free flap reconstruction is the treatment of choice.

Simple Repair of a Blow-Out Fracture by the Modified Caldwell-Luc Approach.

Here we report a patient with a blow-out fracture of the orbital floor that was treated by an intraoral transmaxillary approach. This 38-year-old man suffered a sudden blow to the periorbital area, which caused prolapse of the orbital contents into the maxillary sinus. The modified Caldwell-Luc approach was used to repair the orbital blow-out fracture and the maxillary sinus during was packed with Frazin gauze for 7 days to prevent recurrence of the prolapse. This was an easy and minimally invasive technique for the management of a blow-out fracture of the orbital floor.

Analysis of Microvascular Free Flap Failure Focusing on the Microscopic Findings of the Anastomosed Vessels.

Microvascular flap reconstruction is known as successful technique, although vascular thrombosis can cause free flap failure. To analyze the histologic characteristics and causes of free flap failure, this clinical study examined failed free flaps, including the microanastomosed sites. This study included a total of 5 failed flaps, including 3 radial forearm free flaps, 1 latissimus dorsi free flap, and 1 fibular free flap, all performed with microvascular reconstruction surgery from 2009 to 2011 at Seoul National University Dental Hospital. At the resection surgeries of the failed nonviable flaps, histologic specimens including the microanastomosed vessels were acquired. For light microscope observation, the slides were stained with hematoxylin and eosin (HE), and also with Masson trichrome. Selected portions of graft tissue were also observed under transmission electron microscope (TEM). It was found that the cause of flap failure was the occlusion of vessels because of thrombi formation. During the microanastomosis, damage to the vessel endothelium occurred, followed by intimal hyperplasia and medial necrosis at the anastomosed site. In the TEM findings, some smooth muscle cells beneath endothelium were atrophied and degenerated. The formation of thrombi and the degeneration of the smooth muscle cells were coincident with vascular dysfunction of graft vessel. The damaged endothelium and the exposed connective tissue elements might initiate the extrinsic pathway of thrombosis at the microanastomotic site. Therefore, it is suggested that accurate surgical planning, adequate postoperative monitoring, and skillful technique for minimizing vascular injury are required for successful microvascular transfer.

Identification of biological components for sialolith formation organized in circular multi-layers.

According to the previous studies of sialolithiasis reported so far, this study is aimed to identify the biological components of sialolith, which show different ultrastructures and chemical compositions from other stones, cholelith and urolith. Twenty-two specimens obtained from 20 patients were examined histologically, and analyzed with micro-CT, scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS), and transmission electron microscopy (TEM). All sialoliths (n = 22) observed in this study showed a central nidus, which was filled with organoid matrix admixed with exosome vesicles, loose calcium apatite crystals, and many bacteria. The micro-CT and SEM observation clearly defined a single or multiple central nidus(es) encircled by highly calcified compact zone. The circular compact zone showed a band-like calcification, about 1-3 mm in thickness, and usually located between the central nidus and the peripheral multilayer zone. But some sialoliths (n = 5) showed severe erosion of compact zone by expanding multilayered zone depending on the level of calcification and inflammation in sialolith. By observing TEM images, many exosome vesicles and degraded cytoplasmic organelles were found in the central nidus, and some epithelial cells were also found in the calcified matrix of peripheral multilayer zone. Particularly, EDS analysis indicated the highest Ca/P ratio in the intermediate compact zone (1.77), and followed by the central nidus area (1.39) and the peripheral multilayer zone (0.87). Taken together, these data suggest that the central nidus containing many inflammatory exosomes and degraded cytoplasmic organelles has a potential to induce a band-like calcification of compact zone, and followed by the additional multilayer deposition of exfoliated salivary epithelial cells as well as salivary materials. Thereby, the calcium apatite-based sialolith is gradually growing in its volume size, and eventually obstructs the salivary flow and provides a site for the bacterial infection.

Effects of 4-hexylresorcinol administration on the submandibular glands in a growing rat model.

BACKGROUND: 4-Hexylresorcinol (4HR) is a food additive and class I histone deacetylase inhibitor. In this study, we examined the effects of 4HR administration on the submandibular gland in a growing rat model. METHODS: Four-week-old rats were used in this study. The experimental group (nine males and eight females) received 12.8 mg/kg of 4HR weekly for 12 weeks. Ten rats (five males and five females) were used as controls. The submandibular glands of rats were collected 12 weeks after the first administration of 4HR. The weight of the glands was measured. Histological analysis, immunoprecipitation-high-performance liquid chromatography (IP-HPLC), and western blotting were performed. RESULTS: The weights of the rat submandibular glands were higher in the experimental groups than in the control group, especially in male rats (P < 0.05). The vascular endothelial growth factor (VEGF) and testosterone in the submandibular glands were more highly expressed in 4HR-treated male rats than in untreated rats, as detected by both western blotting and immunohistochemistry. The IP-HPLC results demonstrated that the expression levels of Ki67, epidermal growth factor, and testosterone in the submandibular glands were higher in 4HR-treated male rats than in untreated rats. CONCLUSIONS: This study demonstrated that the systemic administration of 4HR increased the weight of submandibular glands in male rats. In addition, the testosterone and VEGF expression levels in the submandibular glands increased owing to 4HR administration.

Pentoxifylline-induced protein expression change in RAW 264.7 cells as determined by immunoprecipitation-based high performance liquid chromatography.

Although pentoxifylline (PTX) was identified as a competitive non-selective phosphodiesterase inhibitor, its pharmacological effect has not been clearly elucidated. The present study explored the effect of low dose 10 µg/mL PTX (therapeutic dose) compared to high dose 300 µg/mL PTX (experimental dose) in RAW 264.7 cells through immunoprecipitation-based high performance liquid chromatography (IP-HPLC), immunohistochemistry, and western blot. 10 µg/mL PTX increased the expression of proliferation (Ki-67, PCNA, cyclin D2, cdc25A), epigenetic modification (KDM4D, PCAF, HMGB1), protein translation (DOHH, DHPS, eIF5A1), RAS signaling (KRAS, pAKT1/2/3, PI3K), NFkB signaling (NFkB, GADD45, p38), protection (HSP70, SOD1, GSTO1/2), survival (pAKT1/2/3, SP1, sirtuin 6), neuromuscular differentiation (NSEγ, myosin-1a, desmin), osteoblastic differentiation (BMP2, RUNX2, osterix), acute inflammation (TNFα, IL-1, CXCR4), innate immunity (ß-defensin 1, lactoferrin, TLR-3, -4), cell-mediated immunity (CD4, CD8, CD80), while decreased the expression of ER stress (eIF2α, eIF2AK3, ATF6α), fibrosis (FGF2, CTGF, collagen 3A1), and chronic inflammation (CD68, MMP-2, -3, COX2) versus the untreated controls. The activation of proliferation by 10 µg/mL PTX was also supported by the increase of cMyc-MAX heterodimer and ß-catenin-TCF1 complex in double IP-HPLC. 10 µg/mL PTX enhanced FAS-mediated apoptosis but diminished p53-mediated apoptosis, and downregulated many angiogenesis proteins (angiogenin, VEGF-A, and FLT4), but upregulated HIF1α, VEGFR2, and CMG2 reactively. Whereas, 300 µg/mL PTX consistently decreased proliferation, epigenetic modification, RAS and NFkB signaling, neuromuscular and osteoblastic differentiation, but increased apoptosis, ER stress, and fibrosis compared to 10 µg/mL PTX. These data suggest PTX has different biological effect on RWA 264.7 cells depending on the concentration of 10 µg/mL and 300 µg/mL PTX. The low dose 10 µg/mL PTX enhanced RAS/NFkB signaling, proliferation, differentiation, and inflammation, particularly, it stimulated neuromuscular and osteoblastic differentiation, innate immunity, and cell-mediated immunity, but attenuated ER stress, fibrosis, angiogenesis, and chronic inflammation, while the high dose 300 µg/mL PTX was found to alleviate the 10 µg/mL PTX-induced biological effects, resulted in the suppression of RAS/NFkB signaling, proliferation, neuromuscular and osteoblastic differentiation, and inflammation.