Clinical significance of adjuvant therapy after radical surgery for primary osteosarcoma of the jaws.

BACKGROUND: Osteosarcoma of the jaw is one of the rare malignancies and the role of postoperative adjuvant therapy is unclear. This study explored the efficacy of adjuvant therapy after radical surgery for primary osteosarcoma of the jaw. METHODS: The data were retrospectively analyzed from May 2012 to June 2021. The recurrence rate, disease-free survival (DFS) and 5­year overall survival (OS) rate were calculated by Kaplan-Meier method. Intergroup rates were examined by chi-square test. RESULTS: 125 post-radical surgery patients were included. The median follow-up time was 66 months. Forty five cases suffered recurrence. The recurrence rate was 36.0%, and the 5­year OS rate was 68.8%. In the adjuvant treatment group, twenty eight of 99 patients experienced disease progression. In the surgical treatment alone group, seventeen of 26 patients experienced disease progression. The recurrence rates in the two groups were 28.3 and 65.4%, respectively (χ2 = 12.303, p < 0.001). The 5­year OS rate was 75.8 and 42.3%, respectively (χ2 = 10.734, p = 0.001). The median DFS of the relapse patients was 15.1 months (95% CI:13.00-17.20 months), and the 5­year OS rate was 40.0%. Among them, 28 patients received adjuvant therapy while 17 received surgical treatment alone. The median DFS was 15.7 and 11.5 months, respectively, p = 0.024. The median OS was 69.6 months (95% CI 55.69 ~ 83.51 months) and 62.4 months (95% CI 49.06 ~ 75.74 months), respectively(p = 0.034). CONCLUSION: Adjuvant therapy is one of the effective measures to reduce the relapse rate and improve OS after radical surgery for primary osteosarcoma of the jaw.

Single-cell RNA landscape of intratumoral heterogeneity and immunosuppressive microenvironment in advanced osteosarcoma.

Osteosarcoma is the most frequent primary bone tumor with poor prognosis. Through RNA-sequencing of 100,987 individual cells from 7 primary, 2 recurrent, and 2 lung metastatic osteosarcoma lesions, 11 major cell clusters are identified based on unbiased clustering of gene expression profiles and canonical markers. The transcriptomic properties, regulators and dynamics of osteosarcoma malignant cells together with their tumor microenvironment particularly stromal and immune cells are characterized. The transdifferentiation of malignant osteoblastic cells from malignant chondroblastic cells is revealed by analyses of inferred copy-number variation and trajectory. A proinflammatory FABP4+ macrophages infiltration is noticed in lung metastatic osteosarcoma lesions. Lower osteoclasts infiltration is observed in chondroblastic, recurrent and lung metastatic osteosarcoma lesions compared to primary osteoblastic osteosarcoma lesions. Importantly, TIGIT blockade enhances the cytotoxicity effects of the primary CD3+ T cells with high proportion of TIGIT+ cells against osteosarcoma. These results present a single-cell atlas, explore intratumor heterogeneity, and provide potential therapeutic targets for osteosarcoma.

Impact of chemotherapy cycles and intervals on outcomes of nonspinal Ewing sarcoma in adults: a real-world experience.

BACKGROUND: Adult Ewing sarcoma (ES) is a rare disease, the optimal treatment model is unknown. This study aimed to retrospectively analyze treatment-related prognostic factors of nonspinal ES in Chinese adults. METHODS: Eighty-one patients treated between January 2005 and December 2017 were included in the present study. Thirty-three (40.7%) presented with metastatic disease at diagnosis. Eight patients were submitted to primary surgery followed by chemotherapy, while 73 patients received chemotherapy before and after surgery and/or local radiotherapy. The chemotherapy regimen included 8-17 cycles of vincristine, doxorubicin, and cyclophosphamide (VDC) alternating with ifosfamide and etoposide (IE) every 3 weeks. Clinical outcomes and safety were analyzed. RESULTS: VDC/IE chemotherapy was well tolerated in adult patients with ES. Multivariate Cox regression analyses revealed that chemotherapy of at least 12 cycles was a favorable independent prognostic factor of event-free survival (hazard ratio, 0.558; 95% confidence interval, 0.323-0.965; P = 0.037) and overall survival (hazard ratio, 0.424; 95% confidence interval, 0.240-0.748; P = 0.003). Similarly, a low frequency of chemotherapy delays was an independent prognostic factor of improved OS (hazard ratio, 0.438; 95% confidence interval, 0.217-0.887; P = 0.022). CONCLUSION: Our study suggests that adults with ES should be treated with an aggressive multidisciplinary approach, intensive chemotherapy with adequate cycles and appropriate intervals can be recommended in this group.

Curcumin inhibits the proliferation and invasion of MG-63 cells through inactivation of the p-JAK2/p-STAT3 pathway.

PURPOSE: The aims of this study were to determine the effect of curcumin on osteosarcoma (OS) cells due to inactivation of the p-JAK2/p-STAT3 pathway and evaluate the prognostic value of this pathway in OS. MATERIALS AND METHODS: We exposed a human OS cell line (MG-63) to different concentrations of curcumin. Then, we characterized the effects on MG-63 cells using assays (cell viability, colony formation, cell cycle, wound healing, invasion), flow cytometry, Western blot, immunohistochemical analyses, and tumor xenograft. RESULTS: The half-maximal inhibitory of curcumin for MG-63 cells at 24 hours was 27.6 µM. The number of colonies of MG-63 cells was decreased obviously upon curcumin (10 and 20 µM) treatment. We also found increased accumulation of MG-63 cells in the G2/M phase upon curcumin (10 and 20 µM) treatment. Apoptosis was increased in 10 and 20 µM curcumin-treated MG-63 cells. After incubation of physically wounded cells for 24 hours, the percentage wound width increased upon curcumin exposure. Curcumin obviously decreased the expression of pJAK-2 and pSTAT-3 in MG-63 cells in a dose-dependent manner. Curcumin dose-dependently inhibited the proliferation, migration, and invasion of MG-63 cells and induced arrest of the G0/G1 phase and apoptosis by inhibiting the p-JAK2/p-STAT3 pathway. The linear correlativity between expression of p-JAK2 and STAT3 was very prominent, and both were closely associated with lung metastasis. In vivo study suggested that curcumin suppressed tumor growth through JAK2/STAT3 signaling. CONCLUSION: Curcumin-mediated inhibition of the proliferation and migration of MG-63 cells was associated with inactivation of JAK/STAT signaling.

Macrophage-derived CCL18 promotes osteosarcoma proliferation and migration by upregulating the expression of UCA1.

Osteosarcoma (OS), which is the most common primary malignant bone tumor, has a high incidence of pulmonary metastasis. CCL18 (C-C motif chemokine ligand 18), which is secreted by tumor-associated macrophages (TAMs), has been found to be increased in various tumors and is associated with tumor metastasis. However, the role of CCL18 in OS remains unclear. Here, we evaluated the effect of CCL18 on the OS cell lines MG63 and 143B and explored its potential mechanisms. We found that CCL18 enhanced the proliferation and migration of OS cells and upregulated UCA1 through transcription factor EP300. Subsequently, we further revealed that the downstream Wnt/ß-catenin signaling pathway participated in this process. In addition, the high expression of CCL18 in both tissue and serum from patients was closely related to pulmonary metastasis and poor survival in OS patients. The tumor xenograft models also showed that CCL18 promoted the metastasis of OS cells. Collectively, our study indicated that macrophage-derived CCL18 promotes OS proliferation and metastasis via the EP300/UCA1/Wnt/ß-catenin pathway and that CCL18 may be used as a prognostic marker and therapeutic target of OS. KEY MESSAGES: CCL18 promotes proliferation and migration of osteosarcoma cells by EP300/ UCA1/ Wnt/ß-catenin pathway. CCL18+ TAMs are significantly correlated with pulmonary metastasis and poor survival in osteosarcoma patients. CCL18 may be used as a prognostic marker and therapeutic target for osteosarcoma.

Impact of first-line treatment on outcomes of Ewing sarcoma of the spine.

The optimal first-line treatment for primary Ewing sarcoma (ES) of the spine is unclear, especially when the patients present with acute neurological deficits. This study aimed to retrospectively analyze the effect of first-line treatment with surgery or chemotherapy on neurological and survival outcomes of ES of the spine. 39 patients treated between January 2005 and December 2016 were included in the present analysis. 29 (74.4%) presented with symptomatic spinal cord compression at diagnosis. 21 patients were submitted to primary surgery followed by chemotherapy and local radiotherapy, while 18 patients received induction chemotherapy before surgery and/or local radiotherapy. Neurological deficit before and after treatment, event-free survival and overall survival were analyzed. The results indicated that chemotherapy as the first-line treatment could achieve similar results as primary surgery in preserving neurological function, even in case of major neurological deficits. Compared with primary surgery, induction chemotherapy contributed to a higher rate of en bloc resection with a microscopic negative margin (R0) of primary tumor (72.7% vs. 28.6%, P < 0.05). Multivariate Cox regression analyses revealed that initial chemotherapy was a favorable independent prognostic factor of event-free survival (hazard ratio, 0.215; 95% confidence interval, 0.077-0.596; P = 0.003) and overall survival (hazard ratio, 0.288, 95% confidence interval, 0.098-0.852; P = 0.024). In conclusion, our study suggests that first-line treatment of ES of the spine should be induction chemotherapy, even in case of major neurological deficits.

Lack of association between platelet indices and disease stage in osteosarcoma at diagnosis.

PURPOSE: The purpose of this study was to investigate the relationship between platelet indices [mean platelet volume (MPV), platelet count (PLT), platelet distribution width (PDW) and plateletcrit (PCT)] at diagnosis in osteosarcoma. METHODS: The information of 233 patients with osteosarcoma at diagnosis between 2007 and 2015 was retrospectively reviewed. Clinical parameters such as gender, age, size and site of tumor, and tumor necrosis rate after neoadjuvant chemotherapy were analyzed. RESULTS: No significant difference was noted in the mean values of MPV, PLT, PDW and PCT among stage I, II and III patients. In localized patients, the median disease-free survival (DFS) values were 42 and 22 months in the PLT<300×109/L and ≥300×109/L groups, respectively, but the difference was not statistically significant (P = 0.2611). No difference in the DFS among the three different levels of MPV was observed. CONCLUSION: No significantly different platelet indices were noted among the different stages. Although a shorter median DFS was found in localized patients with PLT≥300×109/L, there was still a lack of strong evidence to demonstrate the association between platelet indices and osteosarcoma.

Safety and efficacy of multilevel vertebroplasty for painful osteolytic spinal metastases: a single-centre experience.

OBJECTIVE: To retrospectively assess the safety and efficacy of percutaneous vertebroplasty (PVP) for painful osteolytic spinal metastases when treating more than three vertebrae per session. METHODS: A total of 153 patients with painful osteolytic spinal metastases underwent PVP. Group A patients (n = 93) underwent PVP at up to three vertebral levels per session. Group B patients (n = 60) underwent PVP at more than three levels in one session. Pain, quality of life (QoL), and mobility were assessed before and after PVP. Minor and major complications were systematically assessed. RESULTS: Both groups experienced significant pain relief and QoL improvement after the intervention (p < 0.001). Mobility improvement was observed in both groups, despite worse mobility status before PVP in group B compared with group A. There was no significant difference between the two groups throughout the follow-up period in overall pain relief and improvement in QoL and mobility. There was also no significant difference between groups in minor and major complications. CONCLUSIONS: Multilevel vertebroplasty is safe and effective for the treatment of multiple osteolytic spinal metastases. Multilevel PVP relieves pain and improves QoL and mobility. KEY POINTS: • Percutaneous vertebroplasty is safe and effective for painful osteolytic spinal metastases. • Multilevel vertebroplasty does not cause more complications than single-level vertebroplasty. • Multiple spinal metastases patients may regain functional independence after multilevel vertebroplasty.

Prognostic value of inflammation-based scores in patients with osteosarcoma.

Systemic inflammation responses have been associated with cancer development and progression. C-reactive protein (CRP), Glasgow prognostic score (GPS), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), and neutrophil-platelet score (NPS) have been shown to be independent risk factors in various types of malignant tumors. This retrospective analysis of 162 osteosarcoma cases was performed to estimate their predictive value of survival in osteosarcoma. All statistical analyses were performed by SPSS statistical software. Receiver operating characteristic (ROC) analysis was generated to set optimal thresholds; area under the curve (AUC) was used to show the discriminatory abilities of inflammation-based scores; Kaplan-Meier analysis was performed to plot the survival curve; cox regression models were employed to determine the independent prognostic factors. The optimal cut-off points of NLR, PLR, and LMR were 2.57, 123.5 and 4.73, respectively. GPS and NLR had a markedly larger AUC than CRP, PLR and LMR. High levels of CRP, GPS, NLR, PLR, and low level of LMR were significantly associated with adverse prognosis (P < 0.05). Multivariate Cox regression analyses revealed that GPS, NLR, and occurrence of metastasis were top risk factors associated with death of osteosarcoma patients.

The prognostic value of D-dimer levels in metastatic osteosarcoma patients treated with second-line chemotherapy.

We performed a retrospective analysis of 32 metastatic osteosarcoma cases to examine the prognostic value of the plasma D-dimer level. We assessed the D-dimer level before second-line chemotherapy (D1) and the D-dimer level after two cycles of second-line chemotherapy (D2). The change in D-dimer level (ΔD) was defined as D2 minus D1. The overall survival (OS) of patients with a high D1 was significantly shorter than those with a low D1 (median OS, 4.7 vs. 16.2 months, P=0.001). Similar results were observed for the D2 (median OS, 4.7 vs. 8.6 months, P=0.033). Multivariable analysis demonstrated that a high D1 (hazard ratio, 3.375; 95% confidence interval, 1.133-10.053; P=0.029) was an unfavorable independent prognostic factor. The mean D2 of 11 patients with stable disease decreased by 0.69 mg/mL compared to the D1 (P = 0.016). The mean D2 increased by 1.47 mg/mL compared to the D1 in 21 patients with progressive disease (P = 0.004). The data suggest that D-dimer may serve as a prognostic biomarker for metastatic osteosarcoma patients treated with second-line chemotherapy.

Vastatin, an Endogenous Antiangiogenesis Polypeptide That Is Lost in Hepatocellular Carcinoma, Effectively Inhibits Tumor Metastasis.

Hepatocellular carcinoma (HCC) is a hypervascular cancer without effective treatment. Here we report that polypeptide of NC1 domain of type VIII collagen (Vastatin) is an endogenous polypeptide expressed in normal liver tissue but lost in the liver of most HCC patients (73.1%). Its expression level is negatively associated with tumor size (P = 0.035) and metastasis (P = 0.016) in HCC patients. To evaluate its potential use as a therapeutic, we constructed a recombinant adeno-associated virus carrying Vastatin (rAAV-Vastatin) to treat HCC in an orthotopic Buffalo rat model. rAAV-Vastatin treatment significantly prolonged the median survival, inhibited tumor growth, and completely prevented metastasis in HCC-bearing rats by decreasing microvessel density and increasing tumor necrosis. No detectable toxicity in nontumor-bearing mice was observed. To investigate its molecular mechanisms, we performed DNA microarray, western blotting assays, and bioinformatic analysis to determine its effect on global gene expression patterns and signal transduction pathways. Our results indicated that rAAV-Vastatin significantly reduced the expressions of Pck1, JAG2, and c-Fos, thus inhibiting the cellular metabolism, Notch and AP-1 signaling pathways, respectively. Hence, we demonstrated for the first time that Vastatin is a novel, safe, and effective antiangiogenic therapeutic and a potential biomarker for HCC.

A prospective study to evaluate the efficacy and safety of oral acetyl-L-carnitine for the treatment of chemotherapy-induced peripheral neuropathy.

The present study aimed to evaluate the efficacy and safety of acetyl-L-carnitine (ALC) for the treatment of chemotherapy-induced peripheral neuropathy (CIPN). The study was carried out as a prospective, randomized, double-blind, placebo-controlled and paralleled clinical study. A total of 239 patients with CIPN were selected as the study subjects. Of the 239 subjects, 118 subjects received 3 g/day ALC orally for 8 weeks and 121 received a placebo. The primary endpoint was improvement of peripheral neuropathy by at least one grade. Patient status was assessed at week 4, 8 and 12 after enrollment into the study. In both the full analysis set (FAS) and the per-protocol set (PPS), peripheral sensory neuropathy was significantly ameliorated in the ALC group with 50.5 and 51.6% patients meeting the primary endpoint at week 8, compared with 24.1 and 23.1% of patients in the placebo group (P<0.001 in both sets). Secondary endpoints, such as the nerve electrophysiological examination and the Karnofsky physical score were also significantly improved in patients receiving ALC treatment, as compared with the placebo group (FAS, P=0.0463 and P=0.022; PPS, P=0.0076 and P=0.0064, respectively). Cancer-associated fatigue was significantly alleviated following ALC treatment in the PPS (P=0.0135). In the safety analysis set, the difference in adverse events incidence between the two groups was not statistically significant (P=0.3903). There were only two severe adverse events in the ALC group, which were not associated with the effect of ALC. In conclusion, the results of the present study demonstrated that in Chinese patients with cancer, oral administration of ALC is effective at ameliorating peripheral sensory neuropathy induced by chemotherapy, as well as reducing of cancer-associated fatigue and improving physical conditions.

Continuous-infusion ifosfamide and doxorubicin combination as second-line chemotherapy for recurrent or refractory osteosarcoma patients in China: a retrospective study.

OBJECTIVE: The aim of this retrospective study was to evaluate the feasibility and efficacy of response to continuous-infusion ifosfamide and doxorubicin combination as second-line chemotherapy for patients with recurrent or refractory osteosarcoma. MATERIALS AND METHODS: Eighteen recurrent or refractory osteosarcoma patients who were treated with continuous-infusion ifosfamide and doxorubicin combination between May 1999 and April 2011 were included in the analysis. Ifosfamide at 12 g/m2 was administered by intravenous continuous infusion over 3 days, and doxorubicin 60 mg/m2 was administered as an intravenous bolus injection on day 1. The combination therapy was repeated every 3 weeks. Treatment was continued until evidence of disease progression or unacceptable toxicity. RESULTS: The patients (ages 7-53 years) received a total of 42 cycles of chemotherapy (median: 2 courses; range: 2-5 courses). The overall response rate was 0% and the disease control rate was 22.3%, with four patients having stable disease. The median time to progression and overall survival time were 2 months (range: 2-5 months) and 9 months (range: 3-29 months), respectively. Major severe toxicities were leucopenia 7 (38.9%), nausea and vomiting 3 (16.7%) and alopecia 9 (50%). There were no treatment-related deaths. CONCLUSIONS: In our experience, continuous-infusion ifosfamide and doxorubicin combination therapy at this dosage and schedule was found to be well tolerated and moderate effective, which could be considered as salvage therapy for patients with recurrent or refractory osteosarcoma. Further assessment is necessary to confirm the safety and efficacy of this treatment.

CD133(+) CD44(+) Cells Mediate in the Lung Metastasis of Osteosarcoma.

CD133 and CD44 are commonly used markers of cancer stem cells (CSCs), which are characterized by their ability for self-renewal and tumorigenicity. However, the clinical value and significance of CD133 and CD44 in lung metastasis of osteosarcoma (OS) remains controversial. The purpose of this study was to investigate whether CD133(+) CD44(+) cells mediates the metastasis of OS. We identified the CD133(+) CD44(+) cells in lung metastatic lesions and OS cell lines, and next demonstrated CD133(+) CD44(+) cells were more aggressive in sphere formation, migration and invasiveness compared with CD133(+) CD44(-) , CD133(-) CD44(+) , or CD133(-) CD44(-) cells. We finally sorted the CD133(+) CD44(+) and CD133(-) CD44(-) cells from Saos-2 cell lines, after intratibial xenograft in nude mice, these cells developed primary tumors, and CD133(+) CD44(+) cells are more potential to form lung metastatic tumors. Thus we concluded that CD133(+) CD44(+) cells may mediate in the lung metastasis of OS.

Heterogeneous expression and biological function of ubiquitin carboxy-terminal hydrolase-L1 in osteosarcoma.

Ubiquitin carboxyl terminal hydrolase 1 (UCHL1), a member of the UCH class of DUBs, has been reported as either an oncogene or a tumor suppressor. However, the molecular mechanism underlying the biological function of UCHL1 in osteosarcoma is still unclear. This study was aimed at elucidating the roles of UCHL1 in regulating the biological behavior of osteosarcoma cells. In this study, we found that UCHL1 was elevated in osteosarcoma compared with normal bone tissue. Moreover, UCHL1 expression level was correlated with tumor maximum diameter, high rate of lung metastases and short survival time. Then, we found that knockdown of UCHL1 in osteosarcoma cell MG63 inhibited cell proliferation and significantly increased cell population in the G1 phase. Several cyclins promoting G1/S phase transition were reduced after UCHL1 knockdown, including cell cycle regulator cyclin D1, cyclin E1 and CDK6. Moreover, inhibition of UCHL1 in MG63 cells dramatically induced cell apoptosis. We also found that down-regulation of UCHL1 in MG63 significantly inhibited cell invasion. Then, we found that there was a positive correlation between UCHL1 expression level and the Akt and ERK phosphorylation status. Finally, in vivo data showed that knockdown of UCHL1 inhibited osteosarcoma growth in nude mice. These results indicate that UCHL1 could work as an oncogene and may serve as a promising therapeutic strategy for osteosarcoma.

Pirarubicin-based chemotherapy displayed better clinical outcomes and lower toxicity than did doxorubicin-based chemotherapy in the treatment of non-metastatic extremity osteosarcoma.

Pirarubicin (THP) is a newer generation anthracycline anticancer drug with antineoplastic efficacy against numerous tumors. Few studies have reported its application and efficiency in anti-osteosarcoma chemotherapeutic strategies. Ninety-six non-metastatic extremity osteosarcoma patients treated with THP or doxorubicin (DOX) in combination with high-dose methotrexate (HDMTX), cisplatin (DDP) and ifosfamide (IFO) within the past 9 years at our hospital were evaluated retrospectively to compare efficacy and side effects. Among the patients, 55.2% were male, 36.5% were ≤14 years old and 59.4% presented with a large tumor (≥1/3 of bone) to our department. The 5-year disease-free survival (DFS) rate of the patients treated with the THP-based chemotherapeutic regimen was 70.2%, significantly higher than that of the DOX-based regimen-treated group (53.1%). The THP-based chemotherapeutic regimen decreased the lung metastatic rate significantly compared with the DOX-based regimen (19.1% vs. 36.7%, P=0.045), as well as the relapse rate (31.9% vs. 49.0%, P=0.067). Both regimens were generally well tolerated. However, while the THP-based chemotherapeutic regimen did not alter toxicity in the hematologic system, liver or kidneys compared with the DOX-based regimen, it showed lower rates of alopecia (63.8% vs. 85.7%, P=0.012), nausea and vomiting (51.1% vs. 79.6%, P=0.003), and mucositis (48.9% vs. 75.6%, P=0.003). THP also resulted in lower cardiac toxicity. Our data demonstrate that the THP-based regimen is better than the DOX-based regimen in terms of the 5-year DFS rate, pulmonary metastasis rate, relapse rate and side effects.

Risk of interstitial lung disease associated with EGFR-TKIs in advanced non-small-cell lung cancer: a meta-analysis of 24 phase III clinical trials.

PURPOSE: To assess the risk of interstitial lung disease (ILD) with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) gefitinib, erlotinib, and afatinib. METHOD: PubMed databases were searched for relevant articles. Statistical analyses were conducted to calculate the summary incidence, odds ratio (OR), and 95% confidence intervals (CIs) by using either random-effects or fixed-effect models. RESULTS: The incidence of all-grade and high-grade (≧ grade 3) ILD associated with EGFR-TKIs was 1.6% (95% CI, 1.0-2.4%) and 0.9% (95% CI, 0.6%-1.4%), with a mortality of 13.0% (95% CI, 7.6-21.6%). Patients treated with EGFR-TKIs had a significantly increased risk of developing all-grade (OR, 1.74; 95% CI, 1.25-2.43; P = 0.001) and high-grade (OR, 4.38; 95% CI, 2.18-8.79; P<0.001) ILD. No significant difference in the risk of ILD was found in sub-group analysis according to EGFR-TKIs, percentage of EGFR mutation, study location, EGFR-TKIs-based regimens, and controlled therapy. CONCLUSIONS: Treatment with EGFR-TKIs is associated with a significantly increased risk of developing ILD.

Risk of anti-EGFR monoclonal antibody-related skin rash: an up-to-date meta-analysis of 25 randomized controlled trials.

PURPOSE: To assess the risk of severe skin rash in cancer patients treated with anti-epidermal growth factor receptor (EGFR)-monoclonal antibodies (MoAbs). METHODS: Databases from PubMed, Web of Science, and abstracts presented at American Society of Clinical Oncology (ASCO) meeting up to 31 June 2013 were searched to identify relevant studies. Eligible studies included prospective randomized controlled trials (RCTs) evaluating MoAbs in cancer patients with adequate data on skin rash and/or acne-like skin rash. RESULTS: A total of 14 270 patients from 25 RCTs were included. The overall incidences of all-grade and high-grade rash were, respectively, as follows: skin rash - 55·4 and 10·5%, and acne-like skin rash - 71·9 and 13·3%. Patients who received MoAbs significantly increased the risk of developing all-grade and high-grade skin rash and acne-like skin rash. Meta-regression indicated that the odds ratio (OR) of high-grade skin rash tended to be higher in the study in which the MoAbs treatment was longer. Additionally, similar results were observed in prespecified subgroup analysis. CONCLUSIONS: In patients with advanced solid tumors, EGFR-MoAbs are associated with an increased risk of developing skin rash and acne-like skin rash, and the risk tends to be associated with EGFR-MoAbs treatment duration. Adequate monitoring and early intervention are recommended to prevent decreased quality of life (QoL) and inconsistent dosing.

KLF8 knockdown suppresses proliferation and invasion in human osteosarcoma cells.

Krüppel-like factor 8 (KLF8) is a transcription factor that is important in the regulation of the cell cycle and has a critical role in oncogenic transformation and epithelial to mesenchymal transition (EMT). EMT is a key process in tumor metastasis. Although overexpression of KLF8 has been observed in a variety of human tumor types, the role of KLF8 in human osteosarcoma is yet to be elucidated. The present study aimed to investigate the biological impact of KLF8 on Saos-2 osteosarcoma cells. KLF8 gene expression was knocked down in vitro using a lentivirus-mediated small interfering (si)RNA method. Cell proliferation and cell cycle distribution were evaluated using 3-(4,5)-dimethylthiahiazo(-z-yl)-3,5-di-phenytetrazoliumromide and colony formation assays, and flow cytometry, respectively. Cell invasion was analyzed using a Transwell® invasion assay. Knockdown of KLF8 was found to significantly inhibit proliferation and invasion in osteosarcoma cells. These data suggest that KLF8 may exhibit an important role in osteosarcoma tumorigenesis and that KLF8 may be a potential therapeutic target for the treatment of osteosarcoma.