Oral risk factors associated with medication-related osteonecrosis of the jaw in patients with cancer.

INTRODUCTION: Bone-modifying agents (BMAs) are indispensable to cancer therapy. However, the number of patients with medication-related osteonecrosis of the jaw (MRONJ) is increasing according to the BMA administration. Oral factors predisposing to development of MRONJ are receiving attention, and oral management is recommended for prevention of MRONJ; however, the strategy and criteria have not yet been established. Therefore, we investigated the oral risk factors associated with MRONJ development in this study. MATERIALS AND METHODS: A retrospective study was carried out on 398 cancer patients who had received oncological-dose BMAs between 2007 and 2018; general health factors, demographic, and dental factors were examined along with MRONJ development in all the patients. The cumulative occurrence rate of MRONJ was calculated using a Kaplan-Meier analysis. Clinical factors were analyzed using the Cox regression analysis. RESULTS: MRONJ occurred in 42 of the 398 patients. The cumulative MRONJ incidence rates were 4.5, 12.9, 17.7, and 21.6% at 1, 2, 3, and 4 years, respectively. Age (p = 0.038), male sex (p = 0.002), initiation of dental interventions before BMA administration (p = 0.020), alveolar bone loss involving more than half the root (p < 0.001), and torus mandibularis (p < 0.001) were significantly associated with MRONJ. CONCLUSIONS: Our findings suggest that patients with alveolar bone loss involving more than half the root on panoramic radiographs and torus mandibularis carry a high risk of MRONJ development. Early dental intervention before BMA administration and oral management during the treatment are important for preventing MRONJ.

Does inflammatory dental disease affect the development of medication-related osteonecrosis of the jaw in patients using high-dose bone-modifying agents?

OBJECTIVES: High-dose bone-modifying agents (BMAs), such as bisphosphonates and denosumab, are essential for the treatment of cancer patients with bone metastases. The incidence of medication-related osteonecrosis of the jaw (MRONJ) is increasing. Inflammatory dental diseases could lead to MRONJ, and hence, they should be managed appropriately. Tooth extractions are commonly advised to prevent dental inflammation; however, the accurate indications for tooth extractions before starting BMA therapy have not been established. Hence, we assessed teeth with inflammatory dental diseases to identify indicators for prophylactic extraction before starting BMA therapy. MATERIALS AND METHODS: We included 745 teeth with inflammatory dental diseases of 212 cancer patients on high-dose BMA therapy. We assessed the relationship between inflammatory dental disease and risk of MRONJ development. Multivariate Cox regression analysis was used for statistical analysis. The cumulative occurrence rate of MRONJ was calculated using the Kaplan-Meier method. RESULTS: MRONJ occurred in 43 of 745 teeth. Teeth characteristics significantly correlated with MRONJ occurrence were mandible (p = 0.009), molar region (p = 0.005), radiopaque changes in bone surrounding the root on orthopantograms obtained at patients' first visits (p < 0.001), and tooth extractions after starting BMA therapy (p < 0.001). CONCLUSIONS: Radiopaque changes in bone surrounding the root are an important radiographic finding that indicates the need for prophylactic tooth extractions before starting BMA therapy. CLINICAL RELEVANCE: Our results suggest that the prophylactic extraction of teeth with radiopaque changes in bone surrounding the root before starting BMA therapy could prevent the onset of MRONJ.

[18F]fluoro-2-deoxyglucose-positron emission tomography for the assessment of histopathological response after preoperative chemoradiotherapy in advanced oral squamous cell carcinoma.

BACKGROUND: [(18)F]fluoro-2-deoxyglucose-positron emission tomography (FDG-PET) is widely used to evaluate tumor metabolic activity. The aim of this study was to evaluate the usefulness of FDG-PET in assessing the histopathological response to preoperative concurrent chemoradiotherapy (CRT) in patients with oral squamous cell carcinoma (OSCC). METHODS: Forty-five patients with resectable advanced OSCC who had received preoperative CRT followed by tumor ablative surgery between January 2004 and December 2011 were included in the study. All patients underwent FDG-PET before and after preoperative CRT. The maximum standardized uptake value (SUVmax) before (pre-SUV) and after preoperative CRT (post-SUV) and the SUVmax reduction rate (ΔSUV %) were used to evaluate the response to preoperative CRT. Correlations among SUVmax, histopathological response, and expression of cancer antigen Ki-67 and hypoxia-inducible factor-1α (HIF-1α) were analyzed. RESULTS: Preoperative CRT significantly reduced intratumoral FDG uptake (P < 0.001). The pre-SUV and post-SUV were significantly lower in patients with a pathological complete response (pCR) than in those with a non-pCR (pre-SUV P = 0.037; post-SUV P = 0.001). ΔSUV % was higher in patients with pCR than in those with non-pCR (P = 0.029). The pre-SUV was significantly correlated with Ki-67 and HIF-1α expression in pretreatment biopsy specimens (Ki-67 P = 0.046, R = 0.292; HIF-1α P = 0.007, R = 0.385). The expression of both Ki-67 and HIF-1α was significantly lower in patients with pCR than in those with non-pCR (Ki-67 P < 0.001; HIF-1α P < 0.001). CONCLUSIONS: Low pre-SUV and post-SUV and high ΔSUV % may predict a good histopathological response to preoperative CRT. Ki-67 and HIF-1α expression in pretreatment biopsy specimens were predictors of histopathological response to preoperative CRT.

Measurement of Thickness at the Inferior Border of the Mandible Using Computed Tomography Images: A Retrospective Study including 300 Japanese Cases.

Vascularised fibular free flaps are integral to reconstructive surgery for head and neck tumours. We investigated the morphological characteristics of the mandible to improve the incidence of plate-related complications after surgery. Using standard radiological software, thickness measurements of the inferior or posterior margin of the mandible were obtained from computed tomography images of 300 patients at seven sites: (1) mandibular symphysis, (2) midpoint between the mandibular symphysis and mental foramen, (3) mental foramen, (4) midpoint between the mental foramen and antegonial notch, (5) antegonial notch, (6) mandibular angular apex (gonion), and (7) neck lateral border of the dentate cartilage. Relationships between age, sex, height, weight, the number of remaining teeth in the mandible, and the thickness of each mandible were also investigated. Measurement point 1 had the largest median mandibular thickness (11.2 mm), and measurement point 6 had the smallest (5.4 mm). Females had thinner measurements than males at all points, with significant differences at points 1, 2, 3, 4, and 7 (p < 0.001). Age and number of remaining teeth in the mandible did not correlate with mandibular thickness; however, height and weight correlated at all points except point 6. Thickness measurements obtained at the sites provide a practical reference for mandibular reconstruction. Choosing the fixation method based on the measured thickness of the mandible at each site allows for sound plating.

Evaluation of soft tissue changes around the nose following subspinal Le Fort â osteotomy.

PURPOSE: This study sought to evaluate the effect of subspinal Le Fort Ⅰ osteotomy (SLFⅠO) and alar base chinch suture (ABCS) in preventing postoperative changes of nasal shape following maxillary movement of advancement-impaction (MAI) or advancement-downward (MAD) by analyzing changes of nasal soft tissue on computed tomography (CT) images. METHODS: Forty-three Japanese patients with dentofacial deformity who underwent orthognathic surgery with SLFⅠO and ABCS were retrospectively examined. Maxillary movement and changes to soft tissues around the nose were analyzed using pre- and postoperative CT. RESULTS: Increased nasal width and alar base width, upturning of the nasal tip and flattening of the nose occurred in both groups, with more prominent changes in MAI. MAD showed horizontal maxillary movement strongly correlated with changes in pronasale and subnasale. Preoperative nasal height correlated negatively with changes to nasal height in both groups, and to nasolabial angle and nasal tip angle in MAD. There were no correlations between the tightness of ABCS during operation and postoperative nasal soft tissue changes including nasal width. CONCLUSION: Postoperative changes to nasal shape following SLFⅠO and ABCS need to be considered with advance movements of the maxilla, regardless of vertical maxillary movement. Postoperative pronasale and subnasale may be estimable from the amount of the maxillary advance movement in MAD. Postoperative changes in nasal shape may be more prominent in cases with low nasal height.

A Sublatissimus Dorsi Abscess Due to Pasteurella multocida Caused by a Cat Scratch.

We encountered a 51-year-old male patient who was not immunocompromised. Thirteen days before his admission, his right forearm was scratched by his pet cat. Swelling, redness, and purulent discharge appeared at the site, but he did not seek medical attention. He developed a high fever and was hospitalized with a diagnosis of septic shock, respiratory failure, and cellulitis on plain computed tomography. After admission, the swelling on his forearm was relieved with empirical antibiotics, but the symptoms spread from his right axilla to his waist. We suspected necrotizing soft tissue infection and made a trial incision in the lateral chest up to the latissimus dorsi, but were unable to prove it. However, an abscess was later found under the muscle layer. Second incisions were made to allow the abscess to drain. The abscess was relatively serous, and no tissue necrosis was observed. The patient's symptoms improved rapidly. In retrospect, the patient probably already had the axillary abscess on admission. It may have been detected at this point if contrast-enhanced computed tomography had been performed, and early axillary drainage may have accelerated the patient's recovery, which could also have prevented the formation of the latissimus dorsi muscle abscess. In conclusion, the Pasteurella multocida infection on the patient's forearm induced a very unusual presentation and caused an abscess to form under the muscle, unlike necrotizing soft tissue infections. Early contrast-enhanced computed tomography may aid earlier and more appropriate diagnosis and treatment in such cases.

Depression of p53-independent Akt survival signals in human oral cancer cells bearing mutated p53 gene after exposure to high-LET radiation.

Although mutations and deletions in the p53 tumor suppressor gene lead to resistance to low linear energy transfer (LET) radiation, high-LET radiation efficiently induces cell lethality and apoptosis regardless of the p53 gene status in cancer cells. Recently, it has been suggested that the induction of p53-independent apoptosis takes place through the activation of Caspase-9 which results in the cleavage of Caspase-3 and poly (ADP-ribose) polymerase (PARP). This study was designed to examine if high-LET radiation depresses serine/threonine protein kinase B (PKB, also known as Akt) and Akt-related proteins. Human gingival cancer cells (Ca9-22 cells) harboring a mutated p53 (mp53) gene were irradiated with 2 Gy of X-rays or Fe-ion beams. The cellular contents of Akt-related proteins participating in cell survival signaling were analyzed with Western Blotting 1, 2, 3 and 6h after irradiation. Cell cycle distributions after irradiation were assayed with flow cytometric analysis. Akt-related protein levels decreased when cells were irradiated with high-LET radiation. High-LET radiation increased G(2)/M phase arrests and suppressed the progression of the cell cycle much more efficiently when compared to low-LET radiation. These results suggest that high-LET radiation enhances apoptosis through the activation of Caspase-3 and Caspase-9, and suppresses cell growth by suppressing Akt-related signaling, even in mp53 bearing cancer cells.

Neuroprotective effects of granulocyte colony-stimulating factor on ischemia-reperfusion injury of the retina.

PURPOSE: It has been reported that granulocyte colony-stimulating factor (G-CSF) provides neuroprotection in models in which neuronal cell death is induced. This research was designed to investigate the effects of G-CSF on neurodegeneration of the inner retinal layer in a rat model of ischemic reperfusion (I/R) injury. MATERIALS AND METHODS: Retinal ischemia was induced by increasing the intraocular pressure to 110 mm Hg for 45 min in the left eyes of the rats. A sham operation was carried out on the right eyes. G-CSF (100 µg/kg/day in 0.3 ml saline) or the same volume of saline was intraperitoneally injected just before the operation and continued for 4 consecutive days (a total of 5 consecutive days). Morphological examinations, including the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, were performed 7 days after I/R induction. The expression of phosphorylated AKT in the retina was examined by Western blot analysis and immunohistochemistry. RESULTS: Cell loss in the ganglion cell layer was more significantly reduced in the I/R-induced eyes of the G-CSF-injected rats than in the I/R-induced eyes of the saline-injected rats (20.3 vs. 6.6%). The inner retinal thickness ratios, such as the inner plexiform layer to the inner limiting membrane/outer nuclear layer and the inner nuclear layer/outer nuclear layer, were significantly better preserved in the I/R-induced eyes of the G-CSF-injected rats than in the I/R-induced eyes of the saline-injected rats. TUNEL assays showed fewer apoptotic cells in the retinal sections of the I/R-induced eyes of the G-CSF-injected rats. The phosphorylation of AKT (p-AKT/AKT) was upregulated in the retinas of the I/R-induced eyes of the G-CSF-injected rats. CONCLUSION: Our results demonstrated that systemic injection of G-CSF can protect retinal ganglion cells and inner retinal layers from I/R injury. The effects could be associated with the activation of AKT.

[A case of advanced upper gingival carcinoma responding completely to concurrent chemoradiotherapy with S-1].

We report a case of advanced upper gingival carcinoma with a contralateral metastatic lymph node invading the maxillary sinus (T4aN2cM0). An 83-year-old man was treated concurrently with chemoradiotherapy and S-1. S-1 (80 mg/body/day) was administered for 2 weeks followed by a 1-week rest period as one course. Radiation therapy involved a total of 60 Gy (2 Gy/day; 5 days/week). There were side effects of mild leucopenia and a grade 2 stomatitis. After the completion of 2 courses and radiation therapy, the primary tumor disappeared, and the patient achieved a pathologically complete response. The metastatic lymph node also completely disappeared. S-1 was then administered in the same regimen for 1 year. Neither local recurrence nor distant metastasis has been detected 2 years after the completion of the concurrent chemoradiotherapy with S-1.

Travelers' vaccines and their adverse events in Nara, Japan.

BACKGROUND: It is important to analyze the types of vaccines in travel clinics to determine the focus points in future practice. METHODS: We retrospectively reviewed the electronic medical records of all patients who visited the travel clinic of Nara Medical University between June 2013 and December 2019 to determine their background and the vaccines administered. The information regarding adverse events of the unapproved vaccines in Japan (Havrix®, Verorab®, Boostrix®, Priorix®, Typhim Vi®, and Mencevax®) was also collected. RESULTS: Of 645 patients, 58.6% were men and the median age was 31 years. Business was the most common travel purpose (34.9%), and Southeast Asia was the most common destination (40.2%). More than 80% of travelers to low- and middle-income countries were vaccinated against hepatitis A, while the rabies vaccination rate was approximately 50%. Typhoid vaccination coverage among travelers to South Asia was approximately 50%. The incidence of adverse events requiring medical consultation, telephonic consultation, or prolonged stay in the examination room was less than 5% for all unapproved vaccines in Japan. CONCLUSION: More patient education is needed to increase the vaccination rate of rabies and typhoid vaccines. Adverse events to unapproved vaccines in Japan were not high and were well-tolerated.

Risk factors for post-extraction bleeding in patients with haemophilia: a retrospective cohort study.

Many guidelines and studies describe haemostatic management protocols for patients with haemophilia, but few have evaluated the risk factors for post-extraction bleeding. This retrospective cohort study was performed to investigate these risks among this group of patients. We used medical records to identify patients with haemophilia who underwent tooth extraction(s) between April 2006 and April 2019 in the Department of Oral and Maxillofacial Surgery at Nara Medical University Hospital, Nara, Japan, and conducted logistic regression analyses to identify risk or protective factors for post-extraction bleeding in procedures involving factor replacement therapy. Post-extraction bleeding was defined as bleeding that could not be stopped by biting down on gauze, and that required medical treatment between 30min and 14 days after the extraction. A total of 151 extractions (84 interventions) in 55 patients fulfilled the inclusion criteria (130 extractions (72 interventions) in 48 patients with haemophilia A, and 21 extractions (12 interventions) in seven patients with haemophilia B). Post-extraction bleeding was observed in nine patients (16.3%), 10 interventions (11.9%), and 12 extractions (7.9%). On average, it occurred six days after the intervention, and on the fifth postoperative day after extractions. Use of mouth splints significantly reduced the risk (odds ratio: 0.13; p=0.01) in patients on factor replacement therapy. We will conduct a prospective study to investigate the optimal type of splint and optimal splint-wearing period.

Fate of developing tooth buds located in relation to mandibular fractures in three infancy cases.

The fate of developing tooth buds located in relation to mandibular fractures was investigated in three infancy cases. Three infants, 2 girls and a boy, aged from 1 year and 5-months old to 2 years and 6-months old, were treated for dislocated mandibular fracture in the symphyseal region by manual reduction and fixation with a thermoforming splint and circumferential wiring under general anesthesia. Fracture healing was uneventful in all cases. A few years later, no obvious deformity of the jaw or malocclusion was observed; however, malformation of the crown was found in one of the permanent teeth on the fracture line in the first case. In the second case, no abnormality was observed in one of the permanent teeth on the fracture line, but the effect on the other tooth could not be evaluated due to abnormality of the tooth probably not related to the injury. In the third case, root formation was arrested in one of the permanent teeth on the fracture line and the tooth was lost early after eruption. The development of tooth buds on the fracture line is not predictable and therefore, should be monitored by regular follow up.

[Dental injury associated with general anesthesia and the preventive measures].

BACKGROUND: It is generally recognized that dental injury during general anesthesia is an important problem. We retrospectively evaluated the profiles of dental injuries during general anesthesia and associated factors for the development of dental injury. METHODS: From January 1999 to December 2008, all medical records of the patients with dental injury during general anesthesia were reviewed. RESULTS: Of 30,845 patients who underwent general anesthesia in the period, the dental injury developed in 110 patients (0.36%) during general anesthesia. The incidence of dental injury was higher in patients above 60 years of age, The patients who had received mouth guards had significantly lower incidence of dental injury compared with those without mouth guards (0.06% vs. 0.37%, P < 0.05). The left upper incisors were involved most commonly in the development of dental injury, and the timing of dental injury was most frequent at the time of tracheal intubation.

Enumerated sparse extraction of important surgical planning features for mandibular reconstruction.

Because implicit medical knowledge and experience are used to perform medical treatment, such decisions must be clarified when systematizing surgical procedures. We propose an algorithm that extracts low-dimensional features that are important for determining the number of fibular segments in mandibular reconstruction using the enumeration of Lasso solutions (eLasso). To perform the multi-class classification, we extend the eLasso using an importance evaluation criterion that quantifies the contribution of the extracted features. Experiment results show that the extracted 7-dimensional feature set has the same estimation performance as the set using all 49-dimensional features.

Relationship between soluble MICA and the MICA A5.1 homozygous genotype in patients with oral squamous cell carcinoma.

NK and cytotoxic T cells play an important role in the elimination of virus-infected and tumor cells through NKG2D activating receptors, which can promote the lysis of target cells by binding to the major histocompatibility complex class I-related chain A (MICA) proteins. Polymorphisms in MICA may influence its binding to the NKG2D. The soluble form of MICA is released from the surface of tumor cells of epithelial origin. Whereas MICA expressed on the cell surface stimulates the immunoreceptor natural killer group 2, member D (NKG2D), the secreted form down-regulates NKG2D activity, thus allowing the tumor to escape immunosurveillance by NKG2D-expressing cells. In this study, we examined the association between MICA gene microsatellite polymorphisms and serum levels of soluble MICA in patients with oral squamous cell carcinoma (OSCC). We found that patients with OSCC were more likely to have the A5.1 allele when compared to healthy subjects and also more likely to be homozygous for this allele (p=0.041). Patients with the homozygous A5.1 genotype had higher levels of soluble MICA (p=0.031) and a lower survival rate (p=0.026).

Anti-tumor effects of fusion cells of type 1 dendritic cells and Meth A tumor cells using hemagglutinating virus of Japan-envelope.

It has been reported that the fusion cells of dendritic cells (DCs) and tumor cells have anti-tumor effects. In this experiment, we examined the anti-tumor effects of fusion cells of bone marrow-derived DC type 1 (DC1) and irradiated tumor cells using a newly commercially available hemagglutinating virus of Japan-envelope (HVJ-E) after cell fusion, in a mouse model. To induce DC1, bone marrow cells (BMCs) from BALB/c mice were cultured with GM-CSF, IL-12 and IFN-gamma. BMC-derived DC1 were fused with 20-Gy-irradiated Meth A cells (BALB/c-derived fibrosarcoma) using HVJ-E. We subcutaneously injected: i) the BMC-derived DC1, or ii) the fusion cells of the DC1 and the irradiated Meth A cells, into Meth A-bearing BALB/c mice. The injection of only DC1 showed a moderate anti-tumor effect, as we previously described. However, the fusion cells were more effective in not only suppressing tumor growth but also prolonging survival. These results suggest that the fusion cells of DC1 and the irradiated tumor cells using HVJ-E were more effective in tumor suppression than DC1 alone.

Maxillofacial fractures sustained during baseball and softball.

AIM: The purpose of this study was to investigate the demographics, the type of impact, the site and the treatment of maxillofacial fractures sustained during baseball and softball to develop an effective preventive strategy. PATIENTS AND METHODS: Data of 82 patients treated for baseball- and softball-related maxillofacial fractures at the Department of Oral and Maxillofacial Surgery, Nara Medical University between 1982 and 2007 were retrospectively analyzed. RESULTS: Injuries were found in 64 men in baseball and 16 men and two women in softball with average ages of 19.6 and 30.0 years, respectively. Fractures were caused by being hit by the ball in 61 patients followed by collision in 16 patients. Fractures of the mandible and the mid-face were found in 44 and 38 patients, respectively. The mental and angle region of the mandible and zygoma and alveolar bone of the maxilla were frequently involved. Treatment was mostly conservative. Open reduction and internal fixation were performed only in 15 patients. CONCLUSIONS: Most maxillofacial fractures in these sports were ball-related. Therefore, effective preventive means should be considered to protect against such injuries.

High LET radiation enhances apoptosis in mutated p53 cancer cells through Caspase-9 activation.

Although mutations in the p53 gene can lead to resistance to radiotherapy, chemotherapy and thermotherapy, high linear energy transfer (LET) radiation induces apoptosis regardless of p53 gene status in cancer cells. The aim of this study was to clarify the mechanisms involved in high LET radiation-induced apoptosis. Human gingival cancer cells (Ca9-22 cells) containing a mutated p53 (mp53) gene were irradiated with X-rays, C-ion (13-100 KeV/microm), or Fe-ion beams (200 KeV/microm). Cellular sensitivities were determined using colony forming assays. Apoptosis was detected and quantified with Hoechst 33342 staining. The activity of Caspase-3 was analyzed with Western blotting and flow cytometry. Cells irradiated with high LET radiation showed a high sensitivity with a high frequency of apoptosis induction. The relative biological effectiveness (RBE) values for the surviving fraction and apoptosis induction increased in a LET-dependent manner. Both RBE curves reached a peak at 100 KeV/microm, and then decreased at values over 100 KeV/microm. When cells were irradiated with high LET radiation, Caspase-3 was cleaved and activated, leading to poly (ADP-ribose) polymerase (PARP) cleavage. In addition, Caspase-9 inhibitor suppressed Caspase-3 activation and apoptosis induction resulting from high LET radiation to a greater extent than Caspase-8 inhibitor. These results suggest that high LET radiation enhances apoptosis by activation of Caspase-3 through Caspase-9, even in the presence of mp53.

Association between soluble MICA levels and disease stage IV oral squamous cell carcinoma in Japanese patients.

The soluble form of major histocompatibility complex class I-related chain A (MICA) is released from the surface of tumor cells of epithelial origin. Although MICA expressed on the cell surface stimulates the immunoreceptor natural killer (NK) group 2, member D (NKG2D), the secreted form downregulates NKG2D activity, thus allowing the tumor to escape immunosurveillance by NKG2D-expressing cells. In this study, we examined the association between serum levels of soluble MICA and the severity of disease in patients with oral squamous cell carcinoma (OSCC). We used enzyme-linked immunoabsorbent assay to measure serum levels of soluble MICA in OSCC patients and normal control individuals. Among patients categorized according to most disease parameters tested (tumor size, location, grade of differentiation, regional lymph node status, disease stage), soluble MICA levels in sera did not statistically differ from those in normal control individuals. Patients with stage IV disease and/or regional lymph node metastasis did, however, exhibit significantly higher serum levels of soluble MICA than control individuals (95% confidence interval (CI), 0.65-2.45, p = 0.021, and 95% CI, 0.62-4.42, p = 0.031, respectively). Overall survival rates were significantly higher for OSCC patients with low soluble MICA levels (<50 pg/ml) than for those with high soluble MICA levels (>50 pg/ml) (95% CI, 0.43-2.75, p = 0.03). Serum levels of soluble MICA may be useful in the diagnosis of advanced stage OSCC and as an indicator of regional lymph node metastasis.

Protein microarray analysis of apoptosis-related protein expression following heat shock in human tongue squamous cell carcinomas containing different p53 phenotypes.

PURPOSE: Hyperthermia is useful in the treatment of human head and neck cancers, because it is relatively easy to regulate temperatures when compared to tumors located in deep organs. In this study, attention was focused on p53 as a possible predictive indicator for the efficacy of hyperthermic cancer therapy. METHODS: Two kinds of cell lines were used. These were derived from a human squamous cell carcinoma (SAS) and had identical genetic backgrounds except for their p53 gene status. It was previously reported that the heat sensitivity and frequency of apoptosis in wild-type p53 cells (SAS/neo) were clearly elevated when compared with mutated p53 cells (SAS/mp53). In order to study the expression of apoptosis related proteins after heat treatment, protein microarray analysis was used. RESULTS: The expression of apoptosis inhibitory proteins such as Bcl-2, Bcl-xL, NF-kappaB, COX2, STAT3, IL-6, and IKKalpha/1 was seen to increase after heat treatment in SAS/mp53 cells, but not in SAS/neo cells. CONCLUSION: The result of these observations indicates that apoptosis inhibitory proteins (such as Bcl-2, Bcl-xL, IL-6, etc.) were highly induced in SAS/mp53 cells after heat treatment when compared to control SAS/neo cells.