Changes in 18F-fluorothymidine and 18F-fluorodeoxyglucose positron emission tomography imaging in patients with head and neck cancer treated with chemoradiotherapy

Objective

This study compared change of ¹⁸F-fluorothymidine (FLT) uptake with that of ¹⁸F-fluorodeoxyglucose (FDG) in head and neck squamous cell cancer (HNSCC) patients during and after treatment and evaluated the utility for early monitoring of response to chemoradiotherapy.

Methods

Thirty patients with newly diagnosed HNSCCs treated with concurrent chemoradiotherapy underwent FLT and FDG PET in pre-treatment (PET1), mid-treatment (PET2) and post-treatment (PET3) stages. The PET images were evaluated quantitatively using maximum standardized uptake values (SUVs). Ratios between SUVs at PET2 and PET3 were also calculated.

Results

According to the SUVs, no significant differences were found with primary site location, cellular differentiation and T category in all PET scans. About a 78 % median decrease in FLT SUV was observed at the total dose (TD) of 30 Gy and no apparent change was observed thereafter. About a 40 % decrease in FDG SUV was observed at TD 30 Gy and significant decreases were then found at the 4- and 6-week time points after the therapy. FLT PET demonstrated no recurrence regions in patients with a PET3/PET2 ratio of <1.5. In comparison, FLT SUVs in PET3 with recurrence were increased more than three times. However, no significant difference was found between the values with recurrence and those with no recurrence in FDG PET.

Conclusion

FLT PET signal change preceded FDG PET change and the increase of FLT uptake after the therapy can imply recurrence or a residual tumor. FLT PET seems promising for early evaluation of chemoradiation effects in HNSCCs.     

An anatomical study of the muscles that attach to the articular disc of the temporomandibular joint

The masticatory muscles are generally described as the muscles that originate from the cranium and insert on the mandible. Some of the masticatory muscles also insert into the articular disc of the temporomandibular joint. Although there are numerous reports of studies on the attachment of the fibers to the disc, most reports discuss only one muscle. We have shown that the masticatory muscles are not simply a group of clearly independent muscles, but that these muscles contain various transitional muscle bundles among the major muscles. From this point of view, we carried out minute dissection of the collective muscles and muscle bundles surrounding the temporomandibular joint. We dissected 40 head halves of 20 Japanese cadavers (10 males, 10 females: average 79.6 yr). After complete removal of the bony elements, the structures surrounding the temporomandibular joint were investigated en‐block. In all specimens, the superior surface of the upper head of lateral pterygoid and the midmedial muscle bundle were attached to the disc. In some specimens, the discotemporal bundle, zygomaticomandibularis, and masseter were attached to the anterior surface of the disc. The total vector of these muscles pulls the disc anteriorly. In contrast, the vector of the muscles to the condylar processes of the mandible pulls the mandible medially. From these observations, it seems that the fibers, which attach to the disc act to steady the disc against the masticatory movement. Clin. Anat. 22:932–940, 2009. © 2009 Wiley‐Liss, Inc.     

Changes of gene expression profiles in macrophages stimulated by angiotensin II--angiotensin II induces MCP-2 through AT1-receptor.

INTRODUCTION: Macrophages play critical roles in the development of atherosclerosis and diabetic nephropathy as well as many inflammatory diseases. Angiotensin II type 1 receptor antagonists (AIIA) are beneficial for the prevention of atherosclerosis and diabetic nephropathy suggesting that angiotensin II (Ang II) promotes the development of these diseases. It has recently been reported that Ang II exerts proinflammatory actions in vivo and in vitro. This study was aimed to clarify the direct effects of Ang II on monocytes/macrophages. MATERIALS AND METHODS: PMA-treated THP-1 cells, a human monocytic leukaemia cell line, were treated with Ang II (10-6 mol/L) for 24 hours with or without AIIA (CV11974). We evaluated gene expression profiles of these cells using DNA microarray system and quantified them by real-time RT-PCR. RESULTS: DNA microarray revealed that in total 19 genes, including monocyte chemoattractant protein (MCP)-2, were up-regulated by Ang II and down-regulated by AIIA. Real-time RT-PCR showed that up-regulation of MCP-2 with Ang II is blocked by the AIIA (CV11974) but not by an AT2-receptor antagonist. CONCLUSIONS: These results suggest that Ang II directly stimulates MCP-2 expression through AT1-receptors in activated macrophages. Ang II may contribute to the persistence or amplification of microinflammation in vessel walls, heart and kidney. Vasculoprotective or renoprotective effects of AIIA might partly depend on direct anti-inflammatory effects on macrophages.     

Potential usage of liposomal 4beta-aminoalkyl-4'-O-demethyl-4-desoxypodophyllotoxin (TOP-53) for cancer chemotherapy

To enhance the therapeutic efficacy as well as to reduce the side effect, we attempted to liposomalize 4beta-aminoalkyl-4'-O-demethyl-4-desoxypodophyllotoxin (TOP-53), a novel and effective topoisomerase II inhibitor. More than 90% of TOP-53 was efficiently incorporated into the liposomes composed of dipalmitoylphosphatidylcholine and cholesterol by remote-loading method. Anti-tumor activity of liposomal TOP-53 against solid tumor was examined in vivo using colon26 NL-17 carcinoma model mice. Three doses of liposomal TOP-53 (12 mg/kg/dose) showed significant tumor growth suppression (97.5% reduction determined at day 25) and the increase in life span (33%) of tumor-bearing mice. Furthermore, one mouse out of 5 was completely cured after treatment. Since similar efficacy was observed in the free TOP-53 treated group, liposomalization does not contribute much to the enhancement of therapeutic efficacy. However, a slight but measurable damage at the injection site was observed when free TOP-53 was injected, and the damage was diminished by the liposomalization. Taken together, liposomalization reduces the side effect rather than enhancing the therapeutic efficacy when TOP-53 is used.     

Cancer chemotherapy by liposomal 6-[12-(dimethylamino)ethyl]aminol-3-hydroxy-7H-indeno[2,1-clquinolin-7-one dihydrochloride (TAS-103), a novel anti-cancer agent

A novel anti-tumor agent, 6-[[2-(dimethylamino)ethyl]amino]-3-hydroxy-7H-indeno[2,1-c]quinolin-7-one dihydrochloride (TAS-103), effectively inhibits both topoisomerase I and II activities. To enhance anti-tumor efficacy and to reduce the side effects of the agent, liposomalization of TAS-103 was performed. TAS-103 was effectively entrapped in liposomes by a remote-loading method, and was stable at 4 degrees C and in the presence of 50% serum. To evaluate the anti-tumor efficacy of liposomal TAS-103, the growth inhibition against Lewis lung carcinoma cells in vitro and the therapeutic efficacy against solid tumor-bearing mice in vivo were examined. Liposomal TAS-103 showed strong cytotoxic effect against Lewis lung carcinoma cells in a dose dependent manner and effectively suppressed solid tumor growth accompanying longer survival time of tumor-bearing mice in comparison with the mice treated with free TAS-103. These results suggest that liposomal TAS-103 is useful for cancer therapy.     

Identification of fungi based on the nucleotide sequence homology of their internal transcribed spacer 1 (ITS1) region

In this study, we examined the identification of fungi based on the sequence homology of the internal transcribed spacer 1 (ITS1) region. A newly designed primer pair could amplify the target region of all 42 strains tested. The PCR products were sequenced and the sequence homologies were searched by BLAST. It was demonstrated that this method is a reliable identification method at the genus or species level. At present, available databases are still insufficient to identify some fungi, but with the accumulation of further data in the ITS1 database, this method will be available for the identification of fungi.     

Suicide among psychiatric patients in Fukuoka Prefecture]

To investigate suicide among psychiatric patients in Japan (mainly Fukuoka prefecture), a questionnaire survey was submitted to psychiatrists from departments of psychiatry of university hospitals in Japan, departments of psychiatry of Rosai Hospitals in Japan, psychiatric hospitals in Fukuoka prefecture, psychiatric clinics in Fukuoka prefecture, and departments of psychiatry of general hospitals in Fukuoka prefecture regarding their psychiatric patients who died from suicide (266 females and 267 males). A large proportion of the patients at completed suicide was aged within the thirties to fifties. The majority of patients suffered from either F3 (mood disorders) or F2 (schizophrenia, schizotypal and delusional disorders) categories of the ICD-10 classification. Approximately one-fifth of the patients in Fukuoka prefecture had jobs at the time of completed suicide. The main "occupational risk factors" that were found to be risks for suicide were "failure or overloaded responsibilities in their jobs" and "worsening business situation". The main "other risk factors", i.e., risk factors other than "occupational risk factors" were "worsening psychiatric conditions", "personal life events (e.g., somatic illness or marital discord)" and "life events in other family members (e.g., familial discord or familial problems)". Over 50% of all cases had both "occupational risk factors" and "other risk factors", suggestive of the necessity for multidimensional evaluation and care in the treatment of suicidal patients. Given that numerous males that suffer from psychiatric disorders commit suicide without seeing a psychiatrist, it is important to establish a system to treat them appropriately in order to prevent unnecessary deaths.     

Serum cystatin-C values in children by age and their fluctuation during dehydration

BACKGROUND: Serum creatinine level (Cr) is extensively used as an index of glomerular filtration rate (GFR) with bedside patients. As serum Cr level differ by the muscle volume, the use of serum Cr as an index of GFR has long been considered problematic in children. METHODS: The subjects of this study were 135 healthy children aged from 1 to 15-years-old. As a pathological condition, the changes in serum cystatin C (Cys-C) in the children whose blood urea nitrogen exceeded 20 mg/dL during the acute stage of dehydration were also investigated. RESULTS: The mean serum Cys-C value was 0.67 +/- 0.19 mg/L on the whole. There was not any male-female difference. The mean serum Cys-C values of the 12 cases in the acute stage and the recovery stage were 0.61 +/- 0.12 mg/L and 0.64 +/- 0.14 mg/L, respectively, indicating no significant difference. CONCLUSION: Serum Cys-C is considered as a favorable index of GFR in children because it is not influenced by age and sex. As it is not influenced by the prerenal factors either, serum Cys-C is useful in children over 1-years-old.     

Interim analysis of a phase II trial of cyclophosphamide, epirubicin and 5-fluorouracil (CEF) followed by docetaxel as preoperative chemotherapy for early stage breast carcinoma

PURPOSE: A single-arm phase II multicenter trial of the combination of cyclophosphamide (C), epirubicin (E), and 5-fluorouracil (F) followed by docetaxel as neoadjuvant chemotherapy is being conducted by the Japan Breast Cancer Research Group. This report describes an interim analysis of the clinical response and safety of 79 patients who finished preoperative chemotherapy and surgery. PATIENTS AND METHODS: Patients with operable breast cancer received C at 500 mg/m2, E at 100 mg/m2, and F at 500 mg/m2 every 21 days for 4 cycles followed by docetaxel at 75 mg/m2 every 21 days for 4 cycles. RESULTS: Of the 79 patients evaluable for analysis the median age was 46 years (28-59), and 61 patients (77.2%) had T2 tumors. A total of 312 of 316 (98.7%) cycles of CEF and 296 of 312 (94.9%) cycles of docetaxel were administered. Average total cumulative dose was 92% and 95% for CEF and docetaxel, respectively. The rate and grade of edema, neuropathy, arthralgia and myalgia were higher with docetaxel than with CEF. The overall clinical response rate was 70.9%. Breast conserving surgery was performed in 31 of 42 patients (73.8%) with a base-line tumor size of more than 3 cm. CONCLUSIONS: Interim data suggest that CEF followed by docetaxel is an active and tolerable neoadjuvant chemotherapy regimen. A final analysis is planned for 2005.