Immunoexpression of Metallothionein in Oral Squamous Cell Carcinoma

Background and Objectives

Metallothionein (MT) is a family of ubiquitous low molecular weight (7 kDa), intracellular (cytoplasmic/nuclear), cysteine rich proteins with high affinity for heavy metals, present in both normal cells and neoplastic cells. Increased expression of MT has been reported to be associated with poor prognosis in various tumours. The objectives of the present study were to compare the expression of MT in normal subjects and in patients with oral squamous cell carcinoma (OSCC), to correlate the expression of MT with respect to clinical staging of OSCC and to evaluate the expression of MT with respect to different histopathological grades of OSCC.

Methods

Thirty cases of OSCC were staged clinically and graded histopathologically. Immunohistochemical method was used to detect the expression of MT in OSCC. The scores obtained were documented and compared statistically.

Results

MT immunoreactivity was noticed in all cases of OSCC. A statistically significant difference was observed in immunoreactivity of MT between the normal and OSCC, and in different histopathological grades of OSCC (p = 0.00001*). However, no statistical significance was found in a number of immunopositive cells in different clinical stages of OSCC (p = 0.7573).

Conclusion

The MT immunoexpression increased from low grade to high grade OSCC. Hence, increased expression of MT may be related to poor prognosis in patients with OSCC.     

Immunohistochemical staining of Langerhans cells in HPV-positive and HPV-negative cases of oral squamous cells carcinoma

The Human Papillomavirus (HPV) has been strongly implicated in development of some cases of oral squamous cell carcinoma (OSCC). However, the immunological system somehow reacts against the presence of this virus. Among the cells involved in such mechanism of defense Langerhans cells (LC) stand out, which are responsible for processing and presenting antigens.

Objectives

The purposes of this study were to investigate the presence of HPV DNA and to evaluate the immunohistochemical reactivity for Langerhans cells between HPV-positive and HPV-negative OSCC. Twenty-seven cases of OSSC were evaluated.

Material and Methods

DNA was extracted from paraffin-embedded tissue samples and amplified by Polymerase Chain Reaction (PCR) for the detection of HPV DNA. Viral typing was performed by dot blot hybridization. Immunohistochemistry was performed by the Streptavidin-biotin technique.

Results

From the 27 cases, 9 (33.3%) were HPV-positive and 18 (66.0%) HPV-negative. HPV 18 was the most prevalent viral type (100% cases) and infection with HPV-16 (co-infection) was detected in only 1 case. In the OSCC specimens examined, immunoreactivity to S-100 antibody was detected in all cases, with a mean number of 49.48±30.89 Langerhans cells positive for immunostaining. The mean number of immunostained Langerhans cells was smaller in the HPV-positive cases (38 cells/case) than in the HPV-negative cases (42.5 cells/case), but this difference was not significant (p=0.38).

Conclusions

The low frequency of detection of HPV DNA in OSCC indicates a possible participation of the virus in the development and progression of only a subgroup of these tumors. There was no association between the immunohistochemical labeling for Langerhans cells (S-100+) and HPV infection of in OSSC. These findings suggest that the presence of HPV in such OSCC cases could not alter the immunological system, particularly the Langerhans cells.     

Overexpression of S100A4 as a biomarker of metastasis and recurrence in oral squamous cell carcinoma

S100A4, a biomarker of epithelial mesenchymal transition (EMT), plays an important role in invasion and metastasis by promoting cancer cell motility. In oral squamous cell carcinoma (OSCC), metastasis results in 90% of cancer associated mortality.

Objective

To investigate the role of S100A4 expression as an important component of the epithelial mesenchymal transition (EMT) program in oral squamous cell carcinoma (OSCC).

Material and Methods

S100A4 protein expression was assessed semi-quantitatively by immunohistochemistry in 47 histologically confirmed cases of oral squamous cell carcinoma (OSCC) and 10 normal oral mucosal biopsies. The association between the S100A4 overexpression and the aggressive features of OSCC were analyzed by X2 test.

Results

Moderate to strong cytoplasmic expression of S100A4 was observed in 30 out of 47 specimens of OSCC (64%). Overexpression of S100A4 was significantly associated with the clinical stage, lymph node involvement, metastases, pattern of invasion and recurrence (p<0.05).

Conclusion

S100A4 expression represents an important biomarker of prognostic significance that may be used to identify a subset of patients at high risk of invasion and metast     

Cyclin D1 and Ki-67 expression correlates to tumor staging in tongue squamous cell carcinoma

Background

The immunohistochemical expression of Cyclin D1 and Ki-67 were analyzed in tongue squamous cell carcinomas (SCC), relating them to the clinical and morphological exhibition of these tumors.

Material and Methods

Twenty-nine patients fulfilled the inclusion criteria; clinical data included gender, age, ethnicity and use of licit drugs such as alcohol and tobacco. The TNM staging and histopathological differentiation grading was assessed for each case. In addition, T1 patients were gathered with T2 patients; and T3 patients were gathered with T4 patients to assemble two distinct groups: (T1/T2) and (T3/T4).

Results

The mean follow-up time was 24 months and 30% of the patients died as a consequence of the disease, while 23.3% lived with the disease and 46.7% lived lesion-free. T1 and T2 tumors showed statistically lesser Ki-67 and Cyclin D1 staining when compared to T3 and T4 tumors.

Conclusions

Ki-67 and Cyclin D1 pose as auxiliary tools when determining the progression of tongue SCC at the time of diagnosis. Key words:Carcinoma, squamous cell, cyclin D, immunohistochemistry, Ki-67 antigen, prognosis.     

Evaluation of pretreatment serum interleukin-6 and tumour necrosis factor alpha as a potential biomarker for recurrence in patients with oral squamous cell carcinoma

Background

Oral squamous cell carcinoma (OSCC) constitutes 3 percent of all cancers with predominant occurrence in middle aged and elderly males. Tumour recurrence worsens disease prognosis and decreases quality of life in patients with OSCC. Proinflammatory cytokines such as interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-α) have been suggested to play a certain role in variety of tumours. The aim of this study was to investigate the relationship of pretreatment serum IL-6 and TNF-α levels on tumour recurrence in patients with OSCC in order to identify potential biomarkers for the early detection of disease recurrence.

Material and Methods

The patients with newly diagnosed OSCC were treated and followed from the first visit from November 2006 until January 2008. Serum IL-6 and TNF-α concentrations were measured. The records of the patients were re-examined in July 2012 and data were recorded about cancer characteristics and tumour recurrence. Disease free survival was analyzed by Kaplan-Meier survival curves, log rank test and Cox proportional hazards regression.

Results

Serum IL-6 was shown as an independent risk factor for tumour recurrence.

Conclusions

Pretreatment serum IL-6 concentration may be a useful biomarker for identification of OSCC patients with increased risk of the disease recurrence. Key words: Serum IL-6, serum TNF-α, oral cancer, recurrence.     

Techniques for early diagnosis of oral squamous cell carcinoma: Systematic review

Background and objectives

The diagnosis of early oral potentially malignant disorders (OPMD) and oral squamous cell carcinoma (OSCC) is of paramount clinical importance given the mortality rate of late stage disease. The aim of this study is to review the literature to assess the current situation and progress in this area.

Material and Methods

A search in Cochrane and PubMed (January 2006 to December 2013) has been used with the key words “squamous cell carcinoma”, “early diagnosis” “oral cavity”, “Potentially Malignant Disorders” y “premalignant lesions”. The inclusion criteria were the use of techniques for early diagnosis of OSCC and OPMD, 7 years aged articles and publications written in English, French or Spanish. The exclusion criteria were case reports and studies in other languages.

Results

Out of the 89 studies obtained initially from the search 60 articles were selected to be included in the systematic review: 1 metaanalysis, 17 systematic reviews, 35 prospective studies, 5 retrospective studies, 1 consensus and 1 semi-structured interviews.

Conclusions

The best diagnostic technique is that which we have sufficient experience and training. Definitely tissue biopsy and histopathological examination should remain the gold standard for oral cancer diagnose. In this systematic review it has not been found sufficient scientific evidence on the majority of proposed techniques for early diagnosis of OSCC, therefore more extensive and exhaustive studies are needed. Key words: Squamous cell carcinoma, early diagnosis, oral cavity, potentially malignant disorders, premalignant lesions.     

Prevalence of salivary epstein-barr virus in potentially malignant oral disorders and oral squamous cell carcinoma

Background

To analyze the presence of salivary Epstein-Barr virus (EBV) DNA in oral squamous cell carcinoma and potentially malignant oral disorders.

Material and Methods

Three groups were studied: Group 1 (12 oral squamous cell carcinomas (OSCC)), Group 2 (12 potentially malignant oral disorders (PMD)) and Group 3 (47 healthy controls). EBV DNA salivary analysis was performed by PCR.

Results

The highest percentage of positive salivary EBV DNA corresponded to the OSCC group (58.3%), followed by the PMD group (41.7%) and the controls (40.4%). The differences between groups were not statistically significant, however (p>0.05).

Conclusions

Salivary EBV DNA was more prevalent in OSCC than in PMD or the controls. Key words:EBV DNA, saliva, oral squamous cell carcinoma, oral leukoplakia.     

Nested PCR for detection of HSV-1 in oral mucosa

Background

It has been estimated that 15%-20% of human tumours are driven by infection and inflammation, and viral infections play an important role in malignant transformation. The evidence that herpes simplex virus type 1 (HSV-1) could be involved in the aetiology of oral cancer varies from weak to persuasive. This study aimed to investigate by nested PCR (NPCR) the prevalence of HSV-1 in samples from normal oral mucosa, oral leukoplakia, and oral squamous cell carcinoma (OSCC).

Material and Methods

We investigated the prevalence of HSV-1 in biopsies obtained from 26 fresh, normal oral mucosa from healthy volunteers as well as 53 oral leukoplakia and 27 OSCC paraffin-embedded samples. DNA was extracted from the specimens and investigated for the presence of HSV-1 by nested polymerase chain reaction (NPCR) and DNA sequencing.

Results

HSV-1 was detected in 14 (54%) of the healthy samples, in 19 (36%) of the oral leukoplakia samples, and in 14 (52%) of the OSCC samples. The differences were not statistically significant.

Conclusions

We observed a high incidence of HSV-1 in healthy oral mucosa, oral leukoplakia, and OSCC tissues. Thus, no connection between OSCC development and presence of HSV-1 was detected. Key words:HSV-1, nested PCR, PCR.     

Oral squamous cell carcinoma: clinicopathological features from 346 cases from a single Oral Pathology service during an 8-year period

Epidemiological data from oral squamous cell carcinoma (OSCC) is mostly derived from North American, European and East Asian populations.

Objective

The aim of this study was to report the demographic and clinicopathological features from OSCC diagnosed in an Oral Pathology service in southeastern Brazil in an 8-year period.

Material and Methods

All OSCC diagnosed from 2005 to 2012 were reviewed, including histological analysis of all hematoxylin and eosin stained slides and review of all demographic and clinical information from the laboratory records.

Results

A total of 346 OSCC was retrieved and males represented 67% of the sample. Mean age of the patients was 62.3 years-old and females were affected a decade older than males (p<0.001). Mean time of complaint with the tumors was 10 months and site distribution showed that the border of the tongue (37%), alveolar mucosa/gingiva (20%) and floor of mouth/ventral tongue (19%) were the most common affected sites. Mean size of the tumors was 3.4 cm, with no differences for males and females (p=0.091) and males reported both tobacco and alcohol consumption more frequently than females. Histological grade of the tumors revealed that 27%, 40% and 21% of the tumors were, respectively, classified as well-, moderately- and poorly-differentiated OSCC, 26 cases (7.5%) were microinvasive OSCC and 17 cases were OSCC variants. OSCC in males mostly affected the border of tongue, floor of mouth/ventral tongue and alveolar mucosa/gingival, while they were more frequent on the border of tongue, alveolar mucosa/gingival and buccal mucosa/buccal sulcus in females (p=0.004).

Conclusions

The present data reflect the epidemiological characteristics of OSCC diagnosed in a public Oral Pathology laboratory in southeastern Brazil and have highlighted several differences in clinicopathological features when comparing male and female OSCC-affected patients.     

Relevance of level IIb neck dissection in oral squamous cell carcinoma

Background

The purpose of this study was to determine the prevalence of level IIb metastasis in patients with oral squamous cell carcinomas (OSCCs).

Material and Methods

A prospective analysis of 56 patients with OSCC who underwent surgical treatment of the primary lesion with simultaneous neck dissection was performed. During neck dissection, level IIb lymph nodes were separately removed and processed. Neck dissection was bilateral in 26 patients (46%) and unilateral in 30 patients (54%).

Results

The mean number of nodes found in the level IIb specimens was 4.7 (range: 0-8 nodes). The prevalence of metastasis at level IIb was 0% in pN0 necks and 3.4% in pN+ necks, with an overall prevalence of 1.8%. A significant association between metastasis to level IIb and type of neck dissection was observed. There were no isolated metastases to level IIb without the involvement of other nodes in the remaining neck specimen. Four regional recurrences were observed during follow-up.

Conclusions

Based on our findings, we suggest that dissection of the level IIb region in patients with OSCC may be required only in patients with multilevel neck metastasis or if level IIa metastasis is found intraoperatively. Key words: Oral squamous cell carcinoma, neck dissection, level IIb, metastasis, spinal accessory nerve.     

Effect of eugenol-based root canal sealers on retention of prefabricated metal posts luted with resin cement

Objective

This study evaluated the effect of two different eugenol-based root canal sealers on the retention of prefabricated metal posts luted with adhesive resin cement.

Materials and methods

Thirty prefabricated ParaPosts randomly divided among three groups of 10 each were luted into extracted single-rooted teeth with adhesive resin cement. Two of the groups had been obturated with Gutta–Percha and one of two eugenol-based root canal sealers (Endofil and Tubli-Seal), respectively. The third group was not obturated and served as the control. The forces required for dislodgment of posts from their prepared post spaces were recorded using a universal testing machine. Data were statistically analyzed using one-way ANOVA and Tukey’s multiple range test was used to determine the mean differences.

Results

Endofil and Tubli-Seal groups demonstrated significantly reduced retention compared to the unobturated (control) group (P < 0.05).

Conclusion

Eugenol-based sealers significantly reduced the retention of prefabricated posts luted with adhesive resin cement.     

New Management Strategies of Oral Tongue Cancer in Bangladesh

Introduction

Malignancies of the tongue represent one of the greatest management challenges for the maxillofacial surgeons as well as oncologists, because of the adverse effects of treatment on oral and pharyngeal function, the eventual quality of life, and the poor prognosis of advanced disease. Therefore, it is important to use judgment and experience in determining the best method of treatment.

Material and methods

We reviewed forty cases of oral tongue cancer patients admitted in the Dental and Facio-Maxillary Surgical Oncology department in National Institute of Cancer Research and Hospital, and department of Oral and Maxillofacial Surgery, Dhaka Dental College and Hospital, Dhaka, Bangladesh, during the past four years and followed till the lesion healed or recurred and followed later on upto two years. All cases were thoroughly examined, investigated with routine blood examinations and radiography of the involved region. Preoperative biopsy of the lesion and staging was done in each and every case. Postoperative biopsy was taken where there was a doubt about the possibility of recurrence.

Results

Squamous cell carcinoma (well differentiated) is by far the most common malignancy of the oral tongue. Generally a correlation is recognized between tumor size, nodal presence, metastasis, and eventual prognosis. When surgeons detect oral tongue cancer at an early stage, they can often treat it with surgery or can, often treat it with surgery or radiation. In later stages the cancer may require a combination of surgery, radiation and chemotherapy.

Conclusion

Standard and uniform protocol has not been explored till now for the practice in our country. So current management strategies of oral tongue cancer cannot be underestimated.     

Increased nuclear ?-catenin expression in oral potentially malignant lesions: A marker of epithelial dysplasia

Background

Deregulation of ?-catenin is associated with malignant transformation; however, its relationship with potentially malignant and malignant oral processes is not fully understood. The aim of this study was to determine and compare the nuclear ?-catenin expression in oral dysplasia and oral squamous cell carcinoma (OSCC).

Material and Methods

Cross sectional study. Immunodetection of ?-catenin was performed on 72 samples, with the following distribution: 21 mild dysplasia, 12 moderate dysplasia, severe dysplasia 3, 36 OSCC including 19 well differentiated, 15 moderately differentiated and 2 poorly differentiated. Through microscopic observation the number of positive cells per 1000 epithelial cells was counted. For the statistical analysis, the Kruskal Wallis test was used.

Results

Nuclear expression of ?-catenin was observed in all samples with severe and moderate dysplasia, with a median of 267.5, in comparison to mild dysplasia whose median was 103.75. Only 10 samples (27.7%) with OSCC showed nuclear expression, with statistically significant differences between groups (p < 0.05).

Conclusions

Our results are consistent with most of the reports which show increased presence of ?-catenin in severe and moderate dysplasia compared to mild dysplasia; however the expression of nuclear ?-catenin decreased after starting the invasive neoplastic process. This suggests a role for this protein in the progression of dysplasia and early malignant transformation to OSCC. Immunodetection of ?-catenin could be a possible immune marker in the detection of oral dysplasia. Key words:Oral squamous cell carcinoma (OSCC), ?-catenin, oral dysplasia.     

Effect of the number of abutments on biomechanics of Branemark prosthesis with straight and tilted distal implants

Objective

This study aimed to evaluate the bending moments, and compressive and tensile forces in implant-supported prostheses with three, four or five abutments.

Material and Methods

Ten Pd-Ag frameworks were tested over two master models with: 1) parallel vertical implants, and 2) tilted distal implants. Strain gauges were fixed on the abutments of each master model to measure the deformation when a static load of 50 N was applied on the cantilever (15 mm). The deformation values were measured when the metallic frameworks were tested over three, four or five abutments, and transformed into force and bending moment values. Data were analyzed by ANOVA and Tukey’s test for multiple comparisons at 5% level of significance.

Results

Abutment #1 (adjacent to the cantilever) had the highest values of force and sagittal bending moment for all tests with three, four or five abutments. Independently from the number of abutments, axial force in abutment #1 was higher in the vertical model than in the tilted model. Total moment was higher with three abutments than with four or five abutments. Independently from the inclination of implants, the mean force with four or five abutments was lower than that with three abutments.

Conclusion

The results suggest that in the set-ups with four or five abutments tilted distal implants reduced axial force and did not increase bending moments.     

Expression of epithelial-mesenchymal transition markers at the invasive front of oral squamous cell carcinoma

Oral squamous cell carcinoma (OSCC) is one of the most common malignances. In epithelial-mesenchymal transition (EMT), epithelial cells switch to mesenchymal-like cells exhibiting high mobility. This migratory phenotype is significant during tumor invasion and metastasis.

Objective

: The aim of this study is to evaluate the expression of the EMT markers E-cadherin, N-cadherin and vimentin in OSCC.

Material and Methods

: Immunohistochemical detection of E-cadherin, N-cadherin and vimentin was performed on 20 OSCC samples. Differences in the expression of each protein at the invasive front (IF) and in the central/superficial areas (CSA) of the tumor were assessed. Differences in the expression of each protein at the IF of both histologically high- and low-invasive OSCCs were evaluated. Associations among expression of proteins at the IF were assessed. Correlations between the expression levels of each protein at the IF and the tumor stage and clinical nodal status were also evaluated.

Results

: Reduced expression of E-cadherin was detected in 15 samples (75%). E-cadherin expression was reduced at the IF when compared to the CSA and in high-invasive tumors when compared to low-invasive tumors. All samples were negative for N-cadherin, even though one sample showed an inconspicuous expression. Positive expression of vimentin was observed in 6 samples (30%). Nevertheless, there was no difference in vimentin expression between the IF and the CSA regions or between the low- and high-invasive tumors. Furthermore, no association was observed among protein expression levels at the IF. Finally, no correlations were observed between each protein’s expression levels and tumor stage or clinical nodal status.

Conclusions

: Reduced E-cadherin expression at the IF and its association with histological invasiveness suggest that this protein is a noteworthy EMT marker in OSCC. Although vimentin was also detected as an EMT marker, its expression was neither limited to the IF nor was it related to histological invasiveness.     

Dentoalveolar comparative study between removable and fixed cribs, associated to chincup,in anterior open bite treatment

Objective

The aim of this prospective study was to compare the dentoalveolar effects produced by two types of palatal crib, removable (Rpc+C) and fixed (Fpc+C), combined with chincup in growing patients with anterior open bite.

Material and Methods

Each group comprised 30 patients, in the mixed dentition phase, with similar cephalometric characteristics and skeletal ages. Group 1 (Rpc+C) presented initial mean age of 8.3 years and mean anterior open bite of 4.0 mm. Group 2 (Fpc+C) presented initial mean age of 8.54 years and mean anterior open bite of 4.3 mm. The evaluation period comprised 12 months between initial (T1) and second lateral radiograph (T2). The T2-T1 changes were compared cephalometrically in the 2 groups using the non-paired t-test.

Results

Vertical changes in the posterior dentoalveolar region were similar between the groups (about 1 mm) and no significant differences were found in molar mesialization. The Fpc+C group had in average 1.6 mm more improvement of the overbite as a result of greater maxillary incisor extrusion (1.3 mm). Patients in this group also presented less lingual tipping of maxillary incisors and more mandibular incisors uprighting.

Conclusions

The Fpc+C combination was more efficient in the correction of the negative overbite mainly due to greater extrusion of the maxillary incisors. However, the Rpc+C appliance promoted better upper and lower incisor inclination, resulting in a more adequate overjet.     

Microleakage in conservative cavities varying the preparation method and surface treatment

Objective

To assess microleakage in conservative class V cavities prepared with aluminum-oxide air abrasion or turbine and restored with self-etching or etch-and-rinse adhesive systems.

Material and Methods

Forty premolars were randomly assigned to 4 groups (I and II: air abrasion; III and IV: turbine) and class V cavities were prepared on the buccal surfaces. Conditioning approaches were: groups I/III - 37% phosphoric acid; groups II/IV -self-priming etchant (Tyrian-SPe). Cavities were restored with One Step Plus/Filtek Z250. After finishing, specimens were thermocycled, immersed in 50% silver nitrate, and serially sectioned. Microleakage at the occlusal and cervical interfaces was measured in mm and calculated by a software. Data were subjected to ANOVA and Tukey’s test (α=0.05).

Results

Forty premolars were randomly assigned to 4 groups (I and II: air abrasion; III and IV: turbine) and class V cavities were prepared on the buccal surfaces. Conditioning approaches were: groups I/III - 37% phosphoric acid; groups II/IV -self-priming etchant (Tyrian-SPe). Cavities were restored with One Step Plus/Filtek Z250. After finishing, specimens were thermocycled, immersed in 50% silver nitrate, and serially sectioned. Microleakage at the occlusal and cervical interfaces was measured in mm and calculated by a software. Data were subjected to ANOVA and Tukey’s test (α=0.05).

Conclusion

Marginal seal of cavities prepared with aluminum-oxide air abrasion was different from that of conventionally prepared cavities, and the etch-and-rinse system promoted higher marginal seal at both enamel and dentin margins.     

Golden proportion assessment between maxillary and mandibular teeth on Indian population

PURPOSE

This study evaluated the existence of golden proportion between the widths of the maxillary and mandibular anterior teeth in Indian population.

MATERIALS AND METHODS

The clinical tooth width measurements were recorded with the digital vernier calipers on 576 patients of both sexes in the age group of 21 - 30 years. Flexible ruler was used to determine the width of maxillary and mandibular anterior teeth on the patients by the same operator. The data obtained was statistically analyzed using paired student t-test (α=.05).

RESULTS

The golden proportion was not found between the width of the right central and lateral incisors in 53% of women and 47% of men. The results revealed the golden percentage was rather inconstant in terms of relative tooth width.

CONCLUSION

The golden proportion is an inappropriate method to relate the successive widths of the maxillary anterior teeth in Indian population.     

Effect of light-curing units in shear bond strength of metallic brackets: an in vitro study

Objective

To determine the influence of the light curing units on the shear bond strength of orthodontic brackets.

Material and Methods

Seventy-two premolars were divided into six groups (n=12): Group I: brackets bonded with Transbond and polymerization with halogen light; Group II: Transbond and LED; Group III: Fuji Ortho and halogen light; Group IV: Fuji Ortho and LED; Group V: Fuji Ortho, without acid and halogen light; Group VI: Fuji Ortho, without acid and LED. The groups were tested to shear strength in a universal testing machine at a crosshead speed of 0.5 mm/min. Data were analyzed statistically by ANOVA and Tukey’s test.

Results

The composite resin presented higher shear bond strength than the resin-modified glass ionomer cement (p<0.05). The halogen light and LED sources produced similar shear bond strength (p>0.05).

Conclusion

The shear bond strength was influenced by the material but not by the light-curing unit. The use of LED reduced the experimental time by approximately 60%, with the same curing efficiency.