Prognostic factors analysis of diffuse midline glioma.

PURPOSE: This study retrospectively analyzes cases of diffuse midline glioma treated with radiotherapy, with the aim of investigating the prognosis of the tumor and its influencing factors. METHODS: From January 2018 to November 2022, we treated 64 patients who were pathologically diagnosed with diffuse midline glioma. Among them, 41 underwent surgical resection, and 23 underwent biopsy procedures. All patients received postoperative radiotherapy. We followed up with the patients to determine the overall survival rate and conducted univariate and multivariate analyses on relevant indicators. RESULTS: The median survival time for the entire patient group was 33.3 months, with overall survival rates of 92.9%, 75.4%, and 45.0% at 1 year, 2 years, and 3 years, respectively. Univariate and multivariate analyses indicated that older patients had a better prognosis. CONCLUSION: Patient age is an independent prognostic factor for patients with diffuse midline glioma undergoing radiation therapy.

ABC Transporters in Prorocentrum lima and Their Expression Under Different Environmental Conditions Including Okadaic Acid Production.

Prorocentrum lima is a typical benthic toxic dinoflagellate, which can produce phycotoxins such as okadaic acid (OA). In this study, we identified three ABC transporter genes (ABCB1, ABCC1 and ABCG2) and characterized their expression patterns, as well as OA production under different environmental conditions in P. lima. We found that the three ABC transporters all showed high identity with related ABC proteins from other species, and contained classical features of ABC transport proteins. Among them, ABCG2 was a half size transporter. The three ABC transporter genes displayed various expression profiles under different conditions. The high concentration of Cu2+ could up-regulate ABCB1, ABCC1 and ABCG2 transcripts in P. lima, suggesting the potential defensive role of ABC transporters against metal ions in surrounding waters. Cu2+, in some concentration, could induce OA production; meanwhile, tributyltin inhibited OA accumulation. The grazer Artemia salina could induce OA production, and P. lima displayed some toxicity to the grazer, indicating the possibility of OA as an anti-grazing chemical. Collectively, our results revealed intriguing data about OA production and the expression patterns of three ABC transporter genes. However, we could not find any significant correlation between OA production and expression pattern of the three ABC transporters in P. lima. Our results might provide new molecular insights on the defensive responses of P. lima to the surrounding environment.

Intracranial meningioma surgery in the elderly (over 65 years): prognostic factors and outcome.

BACKGROUND: Meningiomas are more prevalent in elderly individuals; however, the surgical outcome and prognostic factors in this age group are unclear. This retrospective study aimed to identify the prognostic factors of elderly patients with intracranial meningiomas who underwent surgical resection. METHODS: Eighty-six patients (aged ≥ 65) diagnosed with an intracranial meningioma were surgically treated at our department. The clinical, radiological, and follow-up data were retrospectively reviewed. Univariate and multivariate logistic analyses were performed to identify relationships between factors [age, sex, neurological condition, concomitant disease, American Society of Anesthesiology (ASA) classification, preoperative Karnofsky Performance Scale (KPS) score, tumor location and size, peritumoral edema, and Simpson resection grade] and outcome. RESULTS: One patient (1.2 %) died within 30 days of surgery. The morbidity rate was 37.2 %. Postoperative morbidities occurred more frequently in the patients with preoperative neurological deficits than in those without (p = 0.049). Univariate analysis identified significant relationships between a low KPS score (≤ 70) at discharge and preoperative neurological deficits, low preoperative KPS score (≤ 70), and critical tumor location (p < 0.001, p < 0.001, and p = 0.04, respectively). In the multivariate logistic analysis, only the preoperative KPS score remained significant for the KPS score at discharge (p = 0.005); there was no significant association with the most recent KPS score. CONCLUSION: The outcome of intracranial meningioma resection in elderly individuals is favorable if the preoperative KPS score is >70 and no neurological deficits are present. Treatment decisions should be patient-specific, and additional factors should be considered when operations are performed in patients with a low preoperative KPS score or neurological deficits.

Decompressive hemicraniectomy in patients with malignant middle cerebral artery infarction: A systematic review and meta-analysis.

BACKGROUND & PURPOSE: Malignant middle cerebral artery infarctions (mMCAI) are one of the most devastating ischemic strokes, with up to 80% mortality in non-surgically treated patients. With the publication of three European randomized controlled trials (RCTs), decompressive hemicraniectomy (DHC) was recommended in patients with mMCAI who are aged ≤ 60 years. Recently, three other RCTs enrolling patients aged > 60 years were published; thus, it is necessary to update the previous meta-analysis to re-evaluate the effects of DHC in mMCAI. METHODS: A systematic literature search of PubMed, EMBASE, and the Cochrane Library was conducted for published RCTs investigating the effects of DHC in mMCAI. Primary outcomes were mortality and major disability (modified Rankin Scale score: 4-5) among survivors. Secondary outcomes were death or major disability (mRS score > 3), and death or severe disability (mRS score > 4). Effect sizes were expressed in Peto odds ratio (Peto OR) with 95% confidence intervals. RESULTS: Six studies with 314 patients were subjected to meta-analysis. Data showed that DHC, significantly decreased mortality risk, death or major disability (mRS score > 3), and death or severe disability (mRS score > 4); but was associated with a slightly higher proportion of major disability (mRS score: 4-5) among survivors. There were no statistically significant age differences. CONCLUSIONS: Compared to conservative treatment, DHC significantly decreased mortality and improved functional outcome, with a non-significant increase in the proportion of survivors with major disability. Further studies are required for multidimensional evaluation of DHC for mMCAI.

Knockdown of OY-TES-1 by RNAi causes cell cycle arrest and migration decrease in bone marrow-derived mesenchymal stem cells.

OY-TES-1 is a member of the CTA (cancer-testis antigen) group expressed in a variety of cancer and restrictedly expressed in adult normal tissues, except for testis. To determine whether MSCs (mesenchymal stem cells) express OY-TES-1 and its possible roles on MSCs, OY-TES-1 expression in MSCs isolated from human bone marrow was tested with RT (reverse transcription)-PCR, immunocytochemistry and Western blot. Using RNAi (RNA interference) technology, OY-TES-1 expression was knocked down followed by analysing cell viability, cell cycle, apoptosis and migration ability. MSCs expressed OY-TES-1 at both mRNA and protein levels. The down-regulation of OY-TES-1 expression in these MSCs caused cell growth inhibition, cell cycle arrest, apoptosis induction and migration ability attenuation. Through these primary results it was suggested that OY-TES-1 may influence the biological behaviour of MSCs.

The Impostor Phenomenon Among Nursing Students and Nurses: A Scoping Review.

The impostor phenomenon (IP) refers to a false internal experience of low intelligence or ability that is associated with anxiety, depression, psychological distress, and burnout. The emotions associated with the IP affect not only personal mental health but also patient care. To address this issue, we need to completely understand the prevalence of and factors related to the IP and ways to resolve/overcome IP feelings. The aim of this scoping review was to identify the existing evidence regarding the IP among nursing students and nurses and determine gaps that can be addressed in future research. We conducted our study based on the scoping review methodological framework proposed by Arksey and O'Malley (2005) and advanced by Levac et al. (2010). After searching the Embase, PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Library, Web of Science and ProQuest databases, we identified 11 studies for inclusion in this review. We found that while the IP exists in nursing students and nurses, clinical nurse specialist students and final-year nursing students are at significant risk of impostor behavior. We also found that research in the nursing field has focused on the prevalence of and factors related to the IP, but few studies have addressed ways to resolve/overcome IP feelings. Thus, research in this area should be increased. This scoping review presents research gaps that may serve as a starting point for future work on the IP in the nursing field.

High Expression of Fibronectin 1 Predicts a Poor Prognosis in Glioblastoma.

OBJECTIVE: Glioblastoma multiforme (GBM), the most malignant intracranial neoplasm, is associated with a high mortality and recurrence rate due to the aggressive nature and heterogeneity of the tumor. Some of the molecular markers involved in the tumorigenesis of GBM are essential in prognosis, diagnosis, and treatment. Due to the limitations of therapeutic effects, this study aims to explore novel biomarkers with prognostic value and to provide new insights into therapeutic targets. METHODS: The expression profile of mRNAs in GBM was detected by RNA-sequencing, and differentially expressed genes were identified by integrating the data from RNA-seq results and the GEPIA2 database. Of the total 40 hub genes, FN1, P4HB, and PPIB showed prognostic significance based on both GEPIA2 and CGGA databases. The validation of FN1, P4HB, and PPIB expression by qPCR and correlation analysis with clinicopathological features were performed in 41 GBM tissues from our institution. RESULTS: Kaplan-Meier analysis revealed that FN1 and P4HB expressions levels were related to the overall survival (OS) of GBM patients (P<0.05). Multivariate analysis showed that FN1 overexpression (HR=9.199, P=0.002) was an independent and unfavorable prognostic factor for GBM patients. The median survival time was 8.5 months and 21 months for high and low expressions of FN1, respectively. CONCLUSION: It was suggested that FN1 could be an ideal target for prognosis and a potential therapeutic target in GBM.

FMR1NB Involved in Glioma Tumorigenesis Is a Promising Target for Prognosis and Therapy.

OBJECTIVE: Cancer/testis antigen FMR1NB is aberrantly expressed in various types of cancer, but not in normal tissues except for testis. This study aimed to investigate the expression and functional role of FMR1NB in glioma. METHODS: The expression of FMR1NB mRNA and protein was determined using RT-PCR and immunohistochemistry, respectively, in glioma specimens from 83 patients at follow-up. The effects of siRNA-mediated FMR1NB silencing on malignant biological behaviors were evaluated in glioma cell lines A172 and U251. RESULTS: FMR1NB mRNA and protein expression was detected in 58.8% (77/131) and 46.34% (57/123) of glioma tissues, respectively. FMR1NB protein was positively correlated with World Health Organization grade and found to be an independent prognostic marker for poor outcome. Knockdown of FMR1NB induced apoptosis and suppressed proliferation, adhesion, migration, and invasion by modulating the expression of cyclin A, CDK2, caspase-3, E-cadherin, and N-cadherin in A172 and U251 cells. CONCLUSION: Our findings suggest that FMR1NB contributes to the tumorigenesis of glioma cells and may represent a potential prognostic biomarker and an attractive therapeutic target in glioma.

Combination of Recombinant Adenovirus-p53 with Radiochemotherapy in Unresectable Pancreatic Carcinoma.

OBJECTIVE: To assess the safety and efficacy of the combination of recombinant adenovirus-p53 (rAd-p53) with radiochemotherapy for treating unresectable pancreatic carcinoma. METHODS: The eligible patients received concurrent rAd-p53 intratumoral injection and radiochemotherapy. Intratumoral injection of rAd-p53 was guided by B ultrasound. Radiochemotherapy consisted of intensity-modulated radiotherapy (IMRT) at two dose levels and intravenous gemcitabine (Gem). For radiotherapy, gross target volume (GTV) and clinical target volume (CTV) were 55-60 Gy and 45-55 Gy in 25-30 fractions, respectively. Concurrent intravenous gemcitabine was administered at 350 mg/m(2), weekly, for 6 weeks. The primary end points included toxicity, clinical benefit response (CBR) and disease control rate (DCR). The secondary end points included progression-free survival (PFS) and overall survival (OS). RESULTS: Fifteen eligible patients were enrolled. Eight patients (53.3%) were evaluated as CBR and 12 (80%) achieved DCR. The median PFS and OS were 6.7 and 13.8 months, respectively. One-year PFS and OS were 40.0% and 51.1%, respectively. There were 8 (53.3%) patients reported grade 3 toxicities including neutropenia (6 patients, 40%), fever (1 patient, 6.7%) and fatigue (1 patient, 6.7%). There was no grade 4 toxicity reported. CONCLUSION: Combination of rAd-p53 in unresectable pancreatic carcinoma showed encouraging efficacious benefit and was well tolerated. Long-term follow-up is needed to confirm the improvement of PFS and OS.

Identification of Dysregulated microRNAs in Glioma Using RNA-sequencing.

Glioma is the most common malignant brain tumor in central nervous system. Despite advances in the treatment of glioma such as surgery and chemoradiotherapy, most patients are easy to relapse, resulting in adverse clinical outcomes. Hence, effective molecular-targeting treatment may be one of attractive strategies for glioma therapy. The dysregulated microRNAs (miRNAs), one of the candidates of therapeutic targets, are believed to play an important role in the progression of glioma. In this study, we aimed to examine the expression profile of miRNAs in glioma and provide a reference for glioma therapy. Firstly, expression profile of miRNAs in 5 normal brain tissues, 5 low-grade glioma (LGG) tissues and 5 glioblastoma (GBM) tissues was detected by RNA sequencing (RNA-seq). Next, the target genes of differentially expressed miRNAs (DEmiRNAs) were predicted and then GO enrichment and KEGG pathway analysis performed by bioinformatics. Finally, 10 miRNAs which were significantly up- or down-regulated both in GBM and LGG were validated by real-time quantitative PCR (qRT-PCR). RNA-seq results indicated a number of DEmiRNAs in glioma. There were 64 up-regulated miRNAs and 17 down-regulated miRNAs in LGG, and 181 up-regulated miRNAs and 124 down-regulated miRNAs in GBM, respectively. Bioinformatics analysis showed that the target genes of these DEmiRNAs were enriched in various biological processes and signaling pathways such as cell metabolic and developmental process. Selected DEmiRNAs were further confirmed by qRT-PCR. miRNA-10b-5p, miRNA-92b-3p and miRNA-455-5p were significantly up-regulated in both GBM and LGG; while miRNA-542-3p was significantly up-regulated in LGG; miRNA-184 and miRNA-206 were significantly down-regulated in both GBM and LGG; miRNA-766-5p and miRNA-1-3p were significantly down-regulated in GBM. The subject of our study demonstrated several dysregulated miRNAs may serve as a potential therapeutic target for glioma.

The Chinese Society of Clinical Oncology (CSCO) clinical guidelines for the diagnosis and treatment of nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor originating in the nasopharynx and has a high incidence in Southeast Asia and North Africa. To develop these comprehensive guidelines for the diagnosis and management of NPC, the Chinese Society of Clinical Oncology (CSCO) arranged a multi-disciplinary team comprising of experts from all sub-specialties of NPC to write, discuss, and revise the guidelines. Based on the findings of evidence-based medicine in China and abroad, domestic experts have iteratively developed these guidelines to provide proper management of NPC. Overall, the guidelines describe the screening, clinical and pathological diagnosis, staging and risk assessment, therapies, and follow-up of NPC, which aim to improve the management of NPC.

Prognostic and clinicopathological value of melanoma-associated antigen D4 in patients with glioma.

The aim of the present study was to evaluate the clinical importance of melanoma-associated antigen D4 (MAGE-D4) expression in glioma, and to identify it as a valuable prognostic biomarker and therapeutic target. To achieve this, the expression of MAGE-D4 protein in 124 tumor tissues from patients with glioma was measured using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC), and the associations between MAGE-D4expression and clinicopathological factors were evaluated. The survival analysis demonstrated the significant prognostic value of MAGE-D4 in glioma using follow-up data. RT-qPCR and IHC analysis confirmed that MAGE-D4 mRNA and protein expression levels were significantly increased in glioma tissues compared with those in normal brain tissues. The present study demonstrated that the percentage of glioma tissues with high expression of MAGE-D4 mRNA was 67.74%, and the percentage positive for MAGE-D4 protein expression was 78.23%. All patients with high MAGE-D4 expression in cancerous tissues experienced significantly reduced median overall survival (OS; 18.00 vs. 33.29 months; P<0.001) and recurrence-free survival (RFS; 12.7 vs. 28.3 months; P<0.001) times compared with those with low MAGE-D4 expression. In the patients with lower grade glioma [World Health Organization (WHO), I-II], similar results were obtained for the OS (26.11 vs. 57.85 months; P=0.013) and RFS (22.7 vs. 55.3 months; P=0.010) times; however, in patients with high-grade glioma (WHO, III-IV), there were no significant differences between high and low MAGE-D4 expression levels with regard to OS and RFS times (P>0.05). Multivariate analysis indicated that high MAGE-D4 protein expression was an important independent prognostic factor for patients with glioma (hazard ratio, 2.384; P=0.005), and was significantly associated with higher grade glioma (P<0.001). These results indicated that MAGE-D4 may be a potential biomarker for glioma and an important prognostic factor for patients with new or recurring glioma.

Involvement of X-chromosome Reactivation in Augmenting Cancer Testis Antigens Expression: A Hypothesis.

Cancer testis antigens (CTAs) are attractive targets for tumor immunotherapy because of their tumor-specific expression. Since more than half of confirmed CTAs are located on the X-chromosome, we asked whether there is a link between CTA expression and X-chromosomes. Recent reports have shown that reactivation of the inactive X-chromosome, known as X-chromosome reactivation (XCR), a unique phenomenon that exists in many high-risk tumors in women, can transform the expression of many X-linked genes from monoallelic to biallelic. In this review, we discuss the link between CTA and XCR with the hopes of providing some novel insights into tumor biology.

Recombinant Adenovirus-p53 Gene Therapy for Advanced Unresectable Soft-Tissue Sarcomas.

Patients with unresectable advanced soft-tissue sarcomas (STS) receiving radiotherapy or/and chemotherapy still have a poor prognosis. This study aimed to evaluate retrospectively the efficacy and safety of recombinant adenovirus-p53 (rAd-p53) gene therapy combined with radiotherapy and hyperthermia for advanced STS. A total of 71 patients with advanced unresectable STS treated at the authors' center from April 2007 to November 2014 were included. Of these 71 patients, 36 cases received rAd-p53 therapy combined with radiotherapy and hyperthermia (p53 group), while 35 cases received radiotherapy and hyperthermia alone (control group). Short-term therapeutic efficacies, long-term survival outcomes, and adverse events were evaluated and compared between groups. Compared to the control group, the p53 group had a significantly higher disease control rate (83.33% vs. 54.29%; p = 0.008) and a lower progressive disease rate (16.67% vs. 45.71%; p = 0.018). In addition, rAd-p53 treatment significantly improved the progression-free survival and overall survival of STS patients. Cox regression indicated that rAd-p53 treatment significantly reduced the risks for disease progression or death event for STS patients. Furthermore, there was no significant difference in all adverse events, except for transient fever, which occurred in 89% of patients with rAd-p53 therapy. rAd-p53 combined with radiotherapy and hyperthermia can effectively improve the therapeutic efficacy and survival outcomes in patients with advanced unresectable STS, providing a new therapeutic strategy.

[Inhibitory effect of Adp53 and F56 on growth and metastasis of transplantation of the breast tumor in mice].

OBJECTIVE: To investigate the effects of Adp53 and F56 on the growth and lung metastasis of breast cancer. METHODS: The BICR-H1 cells were inoculated into the mammary fatty pad of BALB/C nude mice and NOD/SCID mice to establish breast cancer model. Then the nude mice with xenograft tumor were randomized into group Adp53+F56, Adp53, F56 and control. The NOD/SCID mice with xenograft tumor were randomized into group Adp53+F56, Adp53, F56, Adlacz and control. They were treated for 3 weeks according to the plan, diversity of the volume and histopathology of xenograft tumor of nude mice was observed and the expressions of p53 and VEGF gene, and microvessel density (MVD) were detected by immunohistochemistry. Lung metastasis of breast cancer in NOD/SCID mice was observed. RESULTS: (1) Intratumoral injections of Adp53, F56, and their combination resulted in an inhibition on the growth of xenograft tumor of BICR-H1 cells. The ultimate relative growth volumes of groups Adp53+F56, Adp53, F56 and control were 2.47,4.37,4.69 and 12.49 respectively. (2) After treatment, P53 positive rate of group Adp53+F56, Adp53 increased 9.4%, 6.3% than before respectively, but compared with control group, the difference is not significant (P=0.693); VEGF protein of group Adp53+F56, Adp53 and F56 decreased 21.9%, 9.4% and 3.1% than before respectively, but compared with control group, the difference was not significant (P=0.284). Necrosis and decrease of vessel in the tumor and morphological change of endothelium were observed under light microscope in the groups Adp53+F56, Adp53 and F56. MVD estimated by FVIII-RA staining of group Adp53+F56, Adp53 and F56 were 14.50+/-2.54, 16.28+/-3.44 and 18.06+/-7.66, compared with control group(24.93+/-6.53), the difference is significant (P=0.000). (3) The average number of lung metastasis of NOD/SCID mice in group Adp53+F56, Adp53 and F56 were 1.143+/-0.378, 2.750+/-0.886 and 3.375+/-0.518 respectively, lower than Adlacz group(5.000+/-0.816) and control group (5.670+/-0.817) obviously (P=0.000). CONCLUSION: Adp53 combined with F56 can greatly inhibit growth and metastasis of breast cancer in vivo. The mechanism of anti-tumor effects of Adp53 and F56 may be related to the anti-angiogenesis effect on malignant tumor through inhibiting the expression and activity of VEGF.

Nonmissile Penetrating Head Injuries: Surgical Management and Review of the Literature.

BACKGROUND: Nonmissile penetrating head injuries (NPHIs) in the civilian population are rare but potentially fatal. Although numerous cases have been reported in the literature, the surgical management of such injuries is still ambiguous, especially with development of surgical techniques. Here, we report 5 cases of NPHIs managed with different surgical techniques and review the literature on surgical treatment of these injuries to outline the appropriate management for these patients from a neurosurgical perspective. METHODS: We retrospectively reviewed 5 cases of NPHIs managed surgically in our department. The clinical data were collected, including cause, type of objects, way of penetration, initial clinical evaluation, imaging, surgical intervention, postoperative care, complication, follow-up, and outcome. In addition, a systematic review of the literature was performed in the PubMed database to search for articles on surgical treatment of these injuries. RESULTS: These 5 cases were caused by twisted steel bar, electric welding rod, and sewing needle, respectively. Preoperative imaging, including computed tomography, magnetic resonance imaging, and digital subtraction angiography, was selectively performed to assist the operative plan. Foreign objects were removed surgically in all cases. Postoperative prophylactic administration of antibiotics and anticonvulsants was used to prevent infectious and epileptic complications. Most of the patients achieved a better outcome except for one. CONCLUSIONS: NPHIs can be fatal but they can be managed with satisfactory results by proper preoperative imaging evaluation, rapid appropriate surgical management, and accurate postoperative care. Personalized surgical intervention should be undertaken depending on the mechanism and extent of the NPHI.

Effect and Safety of Recombinant Adenovirus-p53 Transfer Combined with Radiotherapy on Long-Term Survival of Locally Advanced Cervical Cancer.

Detection of exogenous p53 gene and target gene expression in cervical cancer cell lines SiHa and C33A infected by recombinant adenovirus-p53 (rAd-p53) in vitro. The rAd-p53 infection evidently increased the expression of exogenous p53 gene, p21 gene, and Bax gene. The radiosensitization rates of rAd-p53 were 1.19 in SiHa and 1.18 in C33A in vitro. To evaluate the effect and safety of rAd-p53 transfer combined with radiotherapy (RT) in patients with cervical cancer, rAd-p53 transfer combined with radiotherapy (group PRT) in 69 patients with cervical cancer was compared with a control group treated with radiotherapy alone (group RT) in 35 patients with cervical cancer. Patients were intratumorally injected with rAd-p53 (1 × 1012 virus particles) once a week for 6 weeks. Concurrent pelvic RT plus brachytherapy to take point A to 76.0 Gray units (Gy) (range 75-80 Gy). The 5-year overall survival rate of the PRT group was 17.5% higher than that of the RT group (HR = 0.551, 95% CI 0.278-1.095, p = 0.084). The 5-year progress-free survival rate of the PRT group was 17.1% higher than that of the RT group (HR = 0.485, 95% CI 0.234-1.006, p = 0.047). rAd-p53 administration did not increase the adverse events caused by radiotherapy, except for transient fever after rAd-p53 administration. rAd-p53 was safe and biologically active in improving radiotherapeutic survival rates in patients with cervical cancer.

[Recombinant adenovirus-p53 gene therapy combined with radiotherapy for head and neck squamous-cell carcinoma].

OBJECTIVE: To evaluate the efficacy and safety of recombinant adenovirus-p53 gene (Gendicine) therapy combined with radiotherapy for head and neck squamous-cell carcinoma (HNSCC). METHODS: From Oct. 2001 to May 2003, a randomized controlled clinical trial on Gendicine combined with radiation in 36 patients (gene therapy + radiotherapy, GTRT) vs. radiotherapy alone in 33 patients (RT) with HNSCC was completed. In the GTRT group, Gendicine 1 x 10(12) VP (virus particle) was injected intratumorally once a week for eight weeks, and concurrently followed by irradiation. For both groups, the conventional fractionation 2 Gy/f, five fractions a week to a total dose of 70 Gy, was given to either primary tumor or neck lymph nodes. Tumor response was assessed by CT image at 40 Gy, 70 Gy, 2 months after treatment to evaluate the response rate of CR, PR, SD and PD. RESULTS: Wild-type p53 gene significantly enhanced radiotherapeutic effectiveness in patients with HNSCC (P < 0.05). The CR rate of tumors treated by GTRT was increased by nearly 2.31 times more than that of tumors treated by RT alone. No dose-limiting toxicity and adverse events were noted, except transient fever after Gendicine administration. CONCLUSION: Intratumoral injection of Gendicine to HNSCC patients is safe and effective. The apparent improved results of combined therapy with Gendicine and radiation suggest that p53 gene therapy has promising therapeutic potential in cancer treatment.

[Detection of p53 gene change and serum antibody level in phase II clinical trial of ad p53 gene therapy].

OBJECTIVE: To determine the alteration of p53 gene in tumor tissues and to monitor the immunoresponsiveness to anti adenovirus in patients following treatment of recombinant adenovirus-p53 (Adp53, SBN-1) combined with radiation. METHODS: Tumor tissues were collected from 22 patients with malignant tumors at advanced stage before and after treatment with recombinant adenovirus-p53 (Adp53, SBN-1) combined with radiation. Immunohistochemistry was used to detect the p53 expression. Microdissection, PCR, and denaturation high performance liquid chromatography (DHPLC), and DNA sequencing were used to detect the mutation of p53 gene. The levels of the anti-adenovirus antibody SBN-1, IgG and IgM in the serum were detected by using ELISA. RESULTS: p53 positive staining was shown in the nuclei of tumor cells in 6 of 15 tumor samples showing the increase of stability of protein caused by gene mutation. DHPLC and DNA sequencing showed point mutation in 7 of 22 tumor samples. Six of the 7 cases with p53 gene mutation showed complete and partial remission at the degree > 50%, and the 8 cases without p53 gene mutation only showed partial remission or stability of condition. The IgG positive rate was 50% (8/ 16), showing that 50% of the patients had been infected by adenovirus (mainly the types 3, 7, and 11) before. The IgM positive rate was 6% (1/16), showing that most of the patients had not been infected by adenovirus (mainly the types 3, 7, and 11) at that time. The anti-SBN-1 antibody was negative in all patients before the rAd-53 therapy and became positive since the 4th week after the beginning of treatment and the intensity of positivity increased along with the time. CONCLUSION: An effective gene diagnosis system for detecting the p53 gene alteration has been developed.