Open-door laminoplasty with stand-alone autologous bone spacers: evaluation of enlarged laminar arch with CT-multiplanar reconstruction.

OBJECTIVE: The authors aimed to determine the efficacy of open-door laminoplasty with stand-alone autologous bone spacer for preserving enlarged lamina in patients with cervical myelopathy. METHODS: Patients who underwent open-door laminoplasty for cervical myelopathy with stand-alone autologous bone spacer and underwent CT 1 week and 1 year after surgery were included in this study. There were 20 men and 13 women, with an average (range) age of 65.0 (37-86) years. Seventeen patients were younger than 70 years, and 16 patients were older than 70 years. Autogenous bone spacers made from spinous processes were used in all patients. Slits were made on both sides of the spacers. The lamina was raised with a curette, and a spacer was inserted without any sutures. Before surgery and 1 week and 1 year after surgery, the anteroposterior diameter (APD) of the spinal canal was measured using midsagittal-plane CT-multiplanar reconstruction. The bone union rate of the hinge side and autogenous bone spacer of each lamina was determined using CT images obtained 1 year after surgery. Results 1 year after surgery were evaluated using Japanese Orthopaedic Association (JOA) score. RESULTS: The mean ± SD APD increase rate was 56.3% ± 21.3% 1 week after surgery and 51.7% ± 20.6% 1 year later. The average APD decrease rate was 2.9% ± 3.8%. The bone union rate on the hinge side was 100%, and that of autologous bone spacer was 93.8% 1 year after surgery. The mean APD decrease rate was 3.3% in patients younger than 70 years and 2.3% in those older than 70 years. There was no significant difference between the two groups (p > 0.05, nonpaired t-test). The JOA score averaged 10.1 before surgery and 13.3 a year after surgery (total score 17). The average improvement rate was 46.3% ± 26.4%. CONCLUSIONS: The authors devised and implemented a technique for inserting an autologous bone spacer between the opened lamina and lateral mass without sutures. The enlarged spinal canal was maintained 1 year after surgery. This simple method does not require any instrumentation or additional cost to stabilize the opened lamina.

Novel in situ visualisation of rat intestinal absorption of polyphenols via matrix-assisted laser desorption/ionisation mass spectrometry imaging.

Matrix-assisted laser desorption/ionisation mass spectrometry imaging (MALDI-MSI) is presently used in physiological evaluations for visualisation of targets in organs. In the present study, MALDI-MSI was used as a visualisation technique to investigate the intestinal absorption of polyphenols. Nifedipine/phytic acid-aided MALDI-MSI was performed to visualise theaflavin-3'-O-gallate (TF3'G) and epicatechin-3-O-gallate (ECG) in the rat jejunum for 50-µM, 60-min transport experiments. Non-absorbable TF3'G was successfully visualised at the apical region, whereas absorbable ECG was detected throughout the rat jejunum. MALDI-MSI was also performed to determine the transport routes of the target metabolites. Signals corresponding to TF3'G and ECG in the membranes were diminished following treatment with inhibitors targeting the monocarboxylic acid transporter and organic anion transporting polypeptides. Enhanced visualisation of TF3'G was achieved by inhibiting efflux routes. Our findings demonstrated that the present MALDI-MSI can provide critical spatial informations on intestinal absorption of targets, by which TF3'G and ECG were incorporated into intestinal tissues, followed by efflux back to the apical compartment. In addition, MALDI-MSI analyses suggested that TF3'G was resistant to phase II metabolism during the influx/efflux processes, whereas ECG was susceptible to methylation and sulphation reactions. In conclusion, inhibitor-aided MALDI-MSI could serve as a powerful in situ visualisation technique for verifying intestinal transport routes and investigating the metabolism of penetrants.

[Corrigendum] Antitumor effects of IDN5109 on head and neck squamous cell carcinoma.

Oncol Rep 15: [Related article:] 329­334, 2006; DOI: 10.3892/or.15.2.329 After the publication of the article, the authors noted that the relevance of the findings reported in this article on IDN5109 inhibition of growth of head and neck squamous cell carcinoma (HNSCC) is now in question. To examine the antitumor effect of IDN5109, this study was conducted using YCU-H891 and KCC-MS871 cell lines that the authors believed to be HNSCC cell lines. Because different human leukocyte antigen (HLA) was detected in 2 cell lines (KCC-TCM901 and KCC-T873) which were derived from the same patient in an experiment after publication, 16 cell lines established in our institution were analyzed by short tandem repeat (STR) analysis. STR analysis revealed that genotype of KCC-TCM901, YCU-H891 and KCC-MS871 was identical to that of HeLa cells, and that genotype of YCU-T891 was identical to that of YCU-L891, which was considered to be cross-contamination.

[Corrigendum] Antitumor effects of ZD6474 on head and neck squamous cell carcinoma.

Oncol Rep 17: [Related article:] 289­295, 2007; DOI: 10.3892/or.17.2.289 After the publication of the article, the authors noted that the relevance of the findings reported in this article on ZD6474 inhibition of growth of head and neck squamous cell carcinoma (HNSCC) is now in question. To examine the antitumor effect of ZD6474 in vitro and in vivo, this study was conducted using YCU-H891 cell line that the authors believed to be HNSCC cell line. Because different human leukocyte antigen (HLA) was detected in 2 cell lines (KCC-TCM901 and KCC-T873) which were derived from the same patient in an experiment after publication, 16 cell lines established in our institution were analyzed by short tandem repeat (STR) analysis. STR analysis revealed that genotype of KCC-TCM901, YCU-H891 and KCC-MS871 was identical to that of HeLa cells, and that genotype of YCU-T891 was identical to that of YCU-L891, which was considered to be cross-contamination.

[A case report: a repeated cerebrospinal fluid otorrhea].

Cerebrospinal fluid (CSF) otorrhea, leakage of CSF through the ear structures, may occur from a traumatic or operative defect in the skull, tumor, cholesteatoma, or congenital anomalies. A case of repeated CSF otorrhea is uncommon. In this report, we presented a case of a repeated CSF otorrhea which occurred a decade after the first middle ear surgery for chronic otitis media. The first CSF leakage, which might have been due to bone defects in the tegmen at the first middle ear sutgery, was surgically repaired using a transmastoid approach. However, CSF leakage with a meningoencephalocele occurred again 8 years after our first surgery for the CSF and the fistula was repaired using a transmiddle cranial fossa approach. Although 2 years have passed since the surgery, the CSF leakage has not recurred.

Clinical and radiological outcomes of microscopic partial pediculectomy for degenerative lumbar foraminal stenosis.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To investigate the clinical outcomes of microscopic partial pediculectomy for degenerative lumbar craniocaudal foraminal stenosis, risk factors for postsurgical scoliosis progression, and feasibility of postsurgical pedicle screw insertion. SUMMARY OF BACKGROUND DATA: Previous studies have evaluated surgical strategies for degenerative lumbar foraminal stenosis. Although less invasive decompression surgery is an option for surgical treatment, postsurgical instability and salvaging fusion surgery remain as problems. No analysis has focused on the radiological progression and feasibility of pedicle screw setting after pediculectomy. METHODS: Microscopic partial pediculectomy by our original method was performed as a first-choice surgical treatment for lumbar radiculopathy due to degenerative craniocaudal foraminal stenosis. This study included 50 consecutive patients followed up for a minimum of 2 years. Clinical outcomes were evaluated with Japanese Orthopaedic Association (JOA) scores and a numerical rating scale. Radiological changes were obtained from standing radiographs. Foraminal height and the minimum pedicle diameter were measured by reconstructed images on multidetector row computed tomography. RESULTS: The preoperative Japanese Orthopaedic Association score of 14.2 ± 4.2 significantly improved to 21.5 ± 6.2, and 60% of patients were satisfied. The numerical rating scale for lumbar back pain, leg pain, and leg numbness significantly improved. Nine patients (18%) showed lumbar Cobb angle progression of 5° or more within 2 years, and the risk factor for scoliosis progression was surgery at L3-L4 or L4-L5 by multivariate logistic regression analysis. Foraminal height was enlarged from 5.4 mm preoperatively to 8.9 mm postoperatively. The postoperative minimum pedicle diameter was 8.7 ± 1.6 (5.9-11.7) mm. CONCLUSION: Microscopic lumbar partial pediculectomy provided satisfactory clinical outcomes, but early postsurgical scoliosis progression was likely to occur in patients who underwent the surgery at L3-L4 or L4-L5. Even if a second surgical procedure is needed, pedicle screws can be set on the resected pedicle. LEVEL OF EVIDENCE: 4.

Increased total volume and dopamine ß-hydroxylase immunoreactivity of carotid body in spontaneously hypertensive rats.

Under hypertension, it has been reported that the carotid body (CB) is enlarged and noradrenaline (NA) content in CB is increased. Therefore, it is hypothesized that morphological and neurochemical changes in CB are induced in hypertensive animal models. In the present study, we examined the morphological features and dopamine ß-hydroxylase (DBH) immunoreactivity in CB of spontaneously hypertensive rats (SHR/Izm) and Wistar Kyoto rats (WKY/Izm). The CB of SHR/Izm was elongated in terms of the cross section of center and was enlarged in the reconstructed images compared with that of WKY/Izm, and the total volume of CB in SHR/Izm (0.048 ± 0.004 mm³) was significantly (p<0.05) increased compared with the value in WKY/Izm (0.032 ± 0.006 mm³). By immunohistochemistry, immunoreactivity for tyrosine hydroxylase in CB was mainly observed in glomus cells and the immunostaining properties were similar between WKY/Izm and SHR/Izm. On the other hand, DBH immunoreactivity was mainly observed in nerve fibers around blood vessels and observed in a few glomus cells in CB of WKY/Izm. The number of glomus cells with strong DBH immunoreactivity was increased in SHR/Izm compared with that in WKY/Izm. In conclusion, the present study exhibited the enlargement of CB as three-dimensional image and revealed the enhanced immunoreactivity for DBH of glomus cells in SHR/Izm. These results suggest that the morphology of CB is affected by the effect of sympathetic nerve and that the signal transduction from CB is regulated by NA in glomus cells under hypertensive conditions.

Treatment evaluation of metastatic lymph nodes after concurrent chemoradiotherapy in patients with head and neck squamous cell carcinoma.

BACKGROUND: Concurrent chemoradiotherapy (CCRT) is used to treat advanced head and neck cancer. The accuracy of evaluating lymph nodes metastases following CCRT is important for subsequent therapy. PATIENTS AND METHODS: Patients were divided into two groups, the complete response (CR) and the non-CR groups, as determined by imaging and fine-needle aspiration cytology (FNAC) performed 4-8 weeks after the CCRT, and the findings were compared with the clinical characteristics. RESULTS: The sensitivity and the specificity of each evaluation method were as follows: 52.9% and 74.2%, respectively, for computer tomography (CT) and magnetic resonance imaging (MRI); 88.2% and 66.1% for ultrasonography (US); 35.3% and 96.0% for fluorodeoxyglucose-positron emission tomography (FDG-PET) or PET-CT; and 71.4% and 95.6% for FNAC. CONCLUSION: To evaluate the response of lymph node(s) treated by CCRT, US is useful as a positive screening tool and FDG-PET and PET-CT as negative screening tools. FNAC is useful in evaluating suspicious lymph nodes in both positive and negative cases.

Comparison of concurrent chemoradiotherapy versus induction chemotherapy followed by radiation in patients with nasopharyngeal carcinoma.

PURPOSE: The study aimed to evaluate the efficacy of concurrent chemoradiotherapy (CCRT) with platinum-based chemotherapy as a primary treatment for nasopharyngeal carcinoma (NPC) and to further compare the results of CCRT with these of neoadjuvant chemotherapy (NAC) followed by radiotherapy (RT). PATIENTS AND METHODS: Before 1998, 21 patients with NPC received NAC followed by RT (NAC-RT). Between 1999 and 2008, a total of 25 NPC patients received CCRT. The CCRT group received a regimen including docetaxel (50 mg/m(2), day1), cisplatin (CDDP, 60 mg/m(2), day4) and continuous 5-fluorouracil (5-FU) infusion (600 mg/m(2), day 1-5), the TPF regimen, or a regimen including CDDP (60 mg/m(2), day4), continuous 5-FU infusion (600 mg/m(2), day 1-5), methotrexate (MTX, 30 mg/m(2), day 1) and leucovorin (LV, 20 mg/m(2), day 1-5), PFML regimen. The CCRT group received 2 cycles of chemotherapy during definitive RT. The NAC group of patients received a PFML regimen. RESULTS: The overall response rate after CCRT was 96%. The 3-year and 5-year disease-specific survival rates were 75.6% and 60.1%, respectively. In patients receiving NAC-RT, the 3-year and 5-year disease-specific survival rates were 84.1% and 67.3%, respectively. There was no difference observed in terms of survival rates between the group receiving CCRT and that receiving NAC-RT. CONCLUSION: CCRT with the TPF or PFML regimen was tolerable, and the NPC patients receiving this treatment showed excellent survival rates. In comparison to the group receiving NAC-RT, CCRT had no advantage in terms of the survival rate. In the future, the control of distant metastasis might play an important role in improving the survival rate of patients with advanced NPC receiving CCRT.

Two cases of congenital cholesteatoma of the tympanic membrane.

Congenital cholesteatoma of the tympanic membrane is rare, and lesions without a history of otitis media or any other adverse events involving the tympanic membrane are extremely rare. We report two cases of this lesion; one was a 3-year-old girl who underwent removal of a cholesteatoma using retroauricular approach and a partial myringoplasty with an underlay technique, and the other was a 2-year-old girl in whom a cholesteatoma was enucleated without grafting. This disease is thought to be of embryonic origin.

Efficacy of fluoro-2-deoxy-D-glucose positron emission tomography to evaluate responses to concurrent chemoradiotherapy for head and neck squamous cell carcinoma.

OBJECTIVE: This study evaluates the utility of fluorodeoxyglucose-positron emission tomography (FDG-PET) in patients with head and neck squamous cell carcinoma (HNSCC) who received concurrent chemoradiotherapy (CCRT). METHODS: Sixty-five patients were recruited for this study between November 2002 and April 2007. The FDG-PET scan was performed before treatment and 4-6 weeks after treatment. RESULTS: The mean of maximum standardized uptake value (SUVmax) before treatment at the primary tumor site was 8.1 (range, 2-22). The sensitivity of FDG-PET for the diagnosis of primary tumor site was 98%. The mean of SUVmax after treatment was 2.6 (range, 2-5). The sensitivity, specificity, and accuracy of FDG-PET for the diagnosis of primary tumor site after treatment were 100%, 40%, and 46%, respectively. The mean of SUVmax before treatment at the nodal site was 4.7 (range, 2-16). The mean of SUVmax after treatment was 2.0 (range, 2-6.7). The pre-treatment SUVmax of T2, T3, and T4 stages were significantly higher than that of the T1 stage. The N stage had no correlation in terms of the pre-treatment nodal site SUVmax. CONCLUSION: Our results indicate that FDG-PET is a useful imaging method for evaluating the response of CCRT in patients with HNSCC. However, performing FDG-PET 4-6 weeks after treatment may be too early as it may give false-positive results due to fibrosis and scarring.

Examination of the optimal condition on the in vitro sensitivity to telomelysin in head and neck cancer cell lines.

OBJECTIVE: Telomelysin (OBP-301) is a telomerase-specific replication-competent adenovirus with a human telomerase reverse transcriptase (hTERT) promoter. Telomelysin has a strong antitumor effect on a variety of cancers, including head and neck squamous cell carcinoma (HNSCC), and combining telomelysin treatment with paclitaxel or cisplatin enhances the antitumor effect on HNSCC. In the present study, we investigated the relationship between the antitumor activity of telomelysin and tumor cell doubling time(DT), S-phase fraction, and E1A expression. We also investigated whether the antitumor effects of OBP-301-resistant tumor cells are enhanced by cisplatin, paclitaxel, or streptolysin O. METHODS: The tumor cell DT of 17 human HNSCC cell lines was examined. Antitumor activities of telomelysin (OBP-301) for each HNSCC cell line were examined by MTT assay. Cell cycle analysis was conducted by flowcytometry. E1A gene expressions after infection with telomelysin, hTERT, CAR (Cocksackie Adenovirus Receptor), and c-Myc were examined by quantitative PCR, and E1A expressions were examined again after pretreatment with cisplatin, paclitaxel, or streptolysin O. Correlations were analyzed by Spearman's correlation coefficient. RESULTS: There was a significant relationship between telomelysin sensitivity and DT, S-phase fraction and early E1A expression, and pretreatment with cisplatin, paclitaxel, and streptolysin O increased infectivity of telomelysin-resistant HNSCC cell lines. CONCLUSION: These findings are useful for advancing clinical trials, and suggest that adjuvant telomelysin treatment would be effective even in telomelysin-resistant HNSCC cell lines.

Efficacy and toxicity of concurrent chemoradiotherapy in patients with advanced oropharyngeal squamous cell carcinoma.

PURPOSE: The aim of this study was to evaluate the feasibility and toxicity of concurrent chemoradiotherapy (CCRT) with docetaxel, cisplatin (CDDP) and 5-fluorouracil (5-FU) (TPF regimen) or with CDDP, 5-FU, methotrexate and leucovorin (PFML regimen) in previously untreated patients with advanced oropharyngeal squamous cell carcinoma (SCC). METHODS: Fifty-six eligible patients with stage III or IV oropharyngeal SCC were treated with CCRT. Forty-four patients were men and 12 were women, and the average age of the patients was 58.8 years (range, 37-72 years). In the TPF group, patients received CCRT with the TPF regimen [docetaxel (50 mg/m(2), day 1), CDDP (60 mg/m(2), day 4) and a continuous 5-FU infusion (600 mg/m(2)/day, days 1-5)]. In the PFML group, patients received CCRT with the PFML regimen [CDDP (60 mg/m(2), day 4), a continuous 5-FU infusion (600 mg/m(2)/day, days 1-5), methotrexate (30 mg/m(2), day 1) and leucovorin (10 mg/m(2)/day, days 1-5)]. The total radiation dose was between 66.6 and 70.2 Gy. RESULTS: The overall 5-year survival rate was 64.6% in all patients, 68.6% in the resectable group and 47.4% in the unresectable group. The 5-year disease-specific survival rate was 72.2% in all patients, 78.1% in the resectable group and 47.7% in the unresectable group. Regarding clinical stage, the 5-year disease-specific survival rates were 91% in stage III, 72% in stage IVa and 44% in stage IVb. CONCLUSION: CCRT with TPF or PFML regimen for advanced oropharyngeal SCC is tolerable and effective, especially in patients with resectable disease.

Morphological characteristics and peptidergic innervation in the carotid body of spontaneously hypertensive rats.

We examined morphological characteristics of the carotid body of spontaneously hypertensive rats (SHR), those of age-matched normotensive Wistar rats (NWR), and age-matched genetically comparable Wistar Kyoto rats (WKY). We examined the distribution and abundance of four different regulatory neuropeptides: substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP), and neuropeptide Y (NPY) in the carotid bodies of these three strains of rats. The carotid bodies of SHR were larger than those of NWR and WKY. The values of the long axis of the carotid bodies of SHR were significantly larger (1.3 times) than those of NWR and WKY. In the carotid bodies of SHR, the percentage of relatively large vessels was similar to that of the carotid bodies of WKY, although the carotid bodies themselves were significantly larger than in WKY. The density of VIP varicose fibers in the carotid bodies of SHR was lower than in the carotid bodies of WKY, although the density of SP, CGRP and NPY fibers was similar to that of the carotid bodies of NWR and WKY. These findings suggested that VIP was unrelated to enlargement of the carotid body of SHR, but it might modify the sensitivity of chemoreceptors in the carotid body.

Clinical outcomes of microscopic decompression for degenerative lumbar foraminal stenosis: a comparison between patients with and without degenerative lumbar scoliosis.

We performed microscopic lumbar foraminotomy in all the patients diagnosed with degenerative lumbar foraminal stenosis (DLFS) and retrospectively reviewed the clinical outcomes and the factors influencing them. The preoperative Japanese Orthopaedic Association (JOA) score of 13.8 significantly improved to 21.9 postoperatively. Although leg pain reduced in 44 patients (95.7%) immediately after surgery, it recurred in 9 patients (19.6%). The recurrence frequency was significantly higher and the JOA score improvement ratios significantly lower in patients with degenerative lumbar scoliosis (DLS) than in those without DLS. Even among patients with DLS, those with <3° Cobb angle difference between the supine and standing positions showed satisfactory results, with no recurrence. In conclusion, microscopic lumbar foraminotomy for DLFS produced satisfactory clinical outcomes even in patients with DLS. However, the outcomes were poor in patients with unstable DLS.

Mucosal melanoma of the head and neck.

Mucosal melanoma of the head and neck (MMHN) is a rare malignant tumor associated with a poor prognosis. A retrospective study of case records of patients treated at our department between 1992 and 2010 was carried out. Thirteen patients were enrolled. The median age of the patients (3 males and 10 females) was 61 years (range 39-78). The median follow-up period was 48 months (range 10-115). Two common primary sites were the nasal cavity (8 cases) and sinonasal complex (5 cases). Ten patients (77%) received curative surgery. Chemotherapy was administered to 10 patients. In addition, lymphokine-activated killer (LAK) cell therapy was administered to 7 patients as adjunctive immunotherapy after the initial treatment course. The overall 5-year, cause-specific survival rate was 56%. Patients who received adjunctive LAK cell therapy had a survival rate of 67% at 5 years, while patients who did not receive adjunctive LAK cell treatment had a survival rate of 33%. MMHN is associated with a poor survival rate. The most common cause of death is distant metastasis. Surgery, radiotherapy and chemotherapy are common strategies for MMHN, but the control of metastasis is difficult. The use of immunotherapy remains uncommon for MMHN. However, from the viewpoint of a systemic disease, due to its high rate of metastases, immunotherapy using LAK cell treatment may contribute to the improvement of prognosis in patients with MMHN.

Antitumor effects of lapatinib (GW572016), a dual inhibitor of EGFR and HER-2, in combination with cisplatin or paclitaxel on head and neck squamous cell carcinoma.

The epidermal growth factor receptor (EGFR) and a related family member, HER-2, are often overexpressed simultaneously in patients with a variety of malignant tumors, and the combination may cooperatively promote cancer cell growth and survival. Heterodimerization of EGFR and HER-2 has been known to create intense proliferative signals. Lapatinib (GW572016) is a small molecule that is administrated orally and functions as a reversible inhibitor of both EGFR and HER-2 tyrosine kinases. In the present study, we evaluated the antitumor effect of lapatinib on head and neck squamous cell carcinoma (HNSCC) cell lines in vitro and in vivo. In vivo we examined the antitumor effects of combined treatment with lapatinib and either cisplatin or paclitaxel. In vitro lapatinib displayed antiproliferative effects on HNSCC cells. The IC50 of lapatinib ranged between 13.6 and 60.2 microM after 24-h exposure to lapatinib. A correlation was not observed between results of in vitro proliferation assays for lapatinib and the expression of EGFR or HER-2. In vivo lapatinib displayed antitumor activity, and induced apoptosis in nude mice bearing an established xenograft of YCU-H891 cells. Lapatinib did not significantly inhibit angiogenesis. Combination treatment of lapatinib with cisplatin or paclitaxel enhanced antitumor activity mainly by inducing apoptosis. Inhibition of antiangiogenesis was observed only for combination treatment of lapatinib with paclitaxel (compared to vehicle control). These results suggest that: i) lapatinib has antitumor effects in vitro and in vivo; ii) lapatinib may be more effective in combination with cisplatin or paclitaxel; and iii) lapatinib might provide useful clinical benefits to HNSCC patients.

Antitumor effects of telomelysin in combination with paclitaxel or cisplatin on head and neck squamous cell carcinoma.

Telomelysin (OBP-301) is a telomerase-specific replication-component adenovirus. Telomelysin has a human telomerase reverse transcriptase (hTERT) promoter element which efficiently kills human cancer cells, but not normal cells. The present study investigated the correlation between the antitumor effect of telomelysin and mRNA expression of hTERT and coxsackievirus and adenovirus receptor (CAR) in head and neck squamous cell carcinoma (HNSCC) in vitro and whether telomelysin enhances the antitumor effect of paclitaxel or cisplatin, in vivo using a HNSCC xenograft model. We also determined the optimal order for combining telomelysin treatment and chemotherapy as concurrent treatment, telomelysin treatment first and chemotherapy later, chemotherapy first and telomelysin treatment later for achieving the best anticancer effect. The mRNA expression of hTERT and CAR genes was examined by quantitative RT-PCR in 17 HNSCC cell lines. There was no significant correlation between the growth inhibition of telomelysin (ID50 for day 3, 5 and 7) in vitro and mRNA expression levels of hTERT and CAR. Regarding the correlation between CAR expression and telomelysin ID50 for day 3, all cell lines that showed a relative amount of CAR/beta-actin mRNA >0.4 had a low telomelysin ID50. This may indicate that CAR expression contributes to the efficacy of adenovirus infection and the antitumor activity of telomelysin in early stages of treatment. In our in vivo study, combining telomelysin and paclitaxel had an additive effect regardless of treatment order. On the other hand, combining telomelysin and cisplatin had additive effect only when cisplatin treatment preceded telomelysin treatment. These results suggest that paclitaxel is considered innocuous for replication of telomelysin, however cisplatin may influence replication of telomelysin.

Randomized controlled phase II comparison study of concurrent chemoradiotherapy with docetaxel, cisplatin, and 5-fluorouracil versus CCRT with cisplatin, 5-fluorouracil, methotrexate and leucovorin in patients with locally advanced squamous cell carcinoma of the head and neck.

We compared concurrent chemoradiotherapy (CCRT) with docetaxel, cisplatin (CDDP), and 5-fluorouracil (5-FU) (TPF) with CCRT with CDDP, 5-FU, methotrexate and leucovorin (PFML) in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) in terms of safety and efficacy on survival. A total of 100 patients were enrolled. The TPF group received CCRT with the TPF regimen [docetaxel (50 mg/m(2): day 1), CDDP (60 mg/m(2): day 4), and continuous 5-FU infusion (600 mg/m(2)/day: days 1-5)]. In the PFML group, patients received CCRT with the PFML regimen [CDDP (60 mg/m(2): day 4)], continuous 5-FU infusion (600 mg/m(2)/day: days 1-5), methotrexate (30 mg/m(2): day 1) and leucovorin (20 mg/m(2)/day: days 1-5)]. Both groups received 2 cycles of chemotherapy during definitive radiotherapy. The total radiation dose was between 66.6 and 70.2 Gray. The overall response rates after CCRT were 98 with 90% of a pathologically complete response (pCR) in the TPF group and 94 with 77% in the PFML group. For grade 3/4 adverse events, mucositis was more frequent in the PMFL group, and the TPF group showed a higher incidence of hematological toxicity. CCRT with TPF or PMFL for advanced SCCHN was tolerable and produced excellent survival rates.