Expression of deltaNp73 and TAp73alpha independently associated with radiosensitivities and prognoses in cervical squamous cell carcinoma.

PURPOSE: The p73 gene produces different protein isoforms using alternative promoters and splicing, which have different biological characteristics. This study was to investigate the expression patterns of two distinct p73 isoforms (deltaNp73 and TAp73alpha) in cervical squamous cell carcinomas (SCC) and the relationship between their expressions and prognostic significance in cervical SCC patients. EXPERIMENTAL DESIGN: We investigated the protein expressions of deltaNp73 and TAp73alpha in 117 cervical SCC and 113 normal cervical tissues using immunohistochemistry. The expression levels were analyzed with clinical variables and patients' survival. RESULTS: DeltaNp73and TAp73alpha were significantly overexpressed in cervical SCC compared with those in normal cervical epithelium (P < 0.001). However, their expressions were inversely correlated (P < 0.001, R = -0.368) and associated with differential tumor radiosensitivity. Overexpression of deltaNp73 was significantly found in SCC resistant to irradiation (P < 0.001), whereas increase of TAp73alpha expression was observed in the majority of SCC sensitive to irradiation (P < 0.001). Multivariate and survival analyses indicated that the expressions of deltaNp73 and TAp73alpha were independently associated with prognosis: deltaNp73 was associated with recurrence of the disease [P = 0.001; odds ratio (OR), 4.857] and an adverse outcome (P = 0.012; OR, 4.676), whereas TAp73alpha predicted a better survival of cervical SCC patients (P = 0.018; OR, 0.065). CONCLUSIONS: The p73 gene might be an important determinant of cellular response to irradiation. The expressions of the two main isoforms (deltaNp73 and TAp73alpha) might be potential markers for predicting the prognosis and sensitivity to radiotherapy in patients with cervical SCC.     

Treatment of primary g lioblastoma multiforme with c e tuximab, r adiotherapy and t emozolomide (GERT) – phase I/II trial: study protocol

Background  

The implementation of combined radiochemotherapy (RCHT) with temozolomide (TMZ) has lead to a significant increase in overall survival times in patients with Glioblastoma multiforme (GBM), however, outcome still remains unsatisfactory.     

Profiling markers of prognosis in colorectal cancer.

PURPOSE: Colorectal cancer is one of the most common forms of cancer in developed nations and the incidence of this disease is increasing. There is a need to further stratify prognostically distinct groups of colorectal cancer, and the purpose of this study was to identify prognostically significant immunohistochemical marker profiles in colorectal cancer. EXPERIMENTAL DESIGN: In this study, a range (n = 23) of markers [pRb, p16, p21, p27, p53, proliferating cell nuclear antigen, cyclin D1, bcl-2, epidermal growth factor receptor, C-erb-B2, topoisomerase-I, liver fatty acid-binding protein, matrix metalloproteinases (MMP) 1-3, 7, 9, and 13, MT1-MMP, MT2-MMP, and tissue inhibitors of MMP 1-3] of putative prognostic significance have been investigated by immunohistochemistry on formalin-fixed, wax-embedded sections in a series (n = 90) of stage III (Dukes C) colorectal cancers. An immunohistochemical score based on the intensity of immunoreactivity and, where relevant, the proportion of immunoreactive cells was established for each marker. RESULTS: Unsupervised two-dimensional hierarchical cluster analysis identified three distinct cluster groups (designated groups 1-3) with different marker profiles. There were significant survival differences between groups 1 and 2 (log rank = 11.48; P = 0.0007) and between groups 1 and 3 (log rank = 8.32; P = 0.0039). Multivariate analysis showed that the complete marker profile was independently the most significant prognostic factor (hazard ratio, 2.27; 95% confidence interval, 1.15-4.48; P = 0.004). CONCLUSIONS: This study has identified an immunohistochemical marker profile of colorectal cancer and showed that it is an independent indicator of prognosis in this type of cancer.     

大肿块ⅠB、ⅡA期及局部晚期宫颈癌的治疗

宫颈癌是全球范围内严重威胁人类身体健康的疾病，也是中国最常见的妇科恶性肿瘤之一。在尚未开展宫颈涂片普查的国家和地区，患者就诊时肿瘤通常已发展至大肿块ⅠB/Ⅱ期或局部晚期宫颈癌。宫颈癌最常应用的分期系统是FIGO分期系统。尽管分期为早期，但大肿块ⅠB/Ⅱ期宫颈癌的预后与局部晚期患者类似，且单纯子宫切除术无法治愈这类患者。外放射后继以腔内近距离放射联合同期DDP为主的化疗可有效提高局部晚期宫颈癌的总生存率。本文将就目前支持联合治疗大肿块ⅠB/Ⅱ期或局部晚期宫颈癌的临床试验结果进行全面评估。     

NY-ESO-1 119-143 is a promiscuous major histocompatibility complex class II T-helper epitope recognized by Th1- and Th2-type tumor-reactive CD4+ T cells.

The NY-ESO-1 gene product is expressed by a range of human tumors and is recognized by antibodies from sera of cancer patients with NY-ESO-1-expressing tumors. The NY-ESO-1 gene also encodes several MHC class I- and MHC class II-restricted tumor epitopes recognized by T lymphocytes. In particular, we previously reported that the NY-ESO-1 119-143 peptide contains at least two HLA-DRB1*0401-presented epitopes that are recognized by melanoma-reactive CD4+ T cells. Here we report that the NY-ESO-1 119-143 peptide can be presented in the context of multiple HLA-DR alleles to stimulate tumor-reactive CD4+ T cells. The NY-ESO-1 119-143 peptide is able to bind to several DR molecules. The NY-ESO-1 119-143 peptide is also capable of inducing specific CD4+ T cells in vitro from peripheral blood lymphocytes of normal donors and patients with melanoma who express these HLA-DR alleles. These CD4+ T cells recognize NY-ESO-1(+), HLA-matched or autologous melanoma cell lines, as well as autologous antigen-presenting cells fed with the NY-ESO-1 protein. We also demonstrate that the NY-ESO-1 119-143 peptide stimulates in vitro both Th1-type and Th2-type CD4+ T-cell responses from peripheral blood lymphocytes of normal donors and melanoma patients. Taken together, these data suggest a key role of the NY-ESO-1 119-143 peptide sequence in the induction of cellular and humoral responses against NY-ESO-1-expressing tumors. They support the relevance of cancer vaccine trials with the NY-ESO-1 119-143 peptide in the large number of cancer patients with NY-ESO-1-expressing tumors.     

Comparison of the systemic and intratumoral effects of tamoxifen and the aromatase inhibitor vorozole in postmenopausal patients with primary breast cancer.

PURPOSE: To determine biologic differences, if any, between presurgical endocrine treatment with an aromatase inhibitor (vorozole) and tamoxifen in patients with postmenopausal primary breast cancer. PATIENTS AND METHODS: Randomization was to 12 weeks of 2.5 mg of vorozole per day or 20 mg of tamoxifen per day, both orally. Clinical response was assessed monthly together with serum sex hormone binding globulin (SHBG), luteinizing hormone (LH), follicle-stimulating hormone (FSH), estrogens (E1, E2, and E1S), lipids, insulin-like growth factor-1 (IGF-1), and bone metabolites (CrossLaps CTx). Tissue samples for Ki67, apoptotic index (AI), estrogen receptor, and progesterone receptor were collected at 0, 2, and 12 weeks. RESULTS: Ki67 fell by 58% and 43% (means) at 2 weeks in the vorozole and tamoxifen patients, respectively (P =.13). In the vorozole group, the correlations of proportional changes in Ki67 at 2 weeks with tumor volume changes and clinical response at 12 weeks were not significant (P =.09) and marginally significant (P =.04), respectively. Serum lipids did not differ between groups. Serum levels of EI, E2, and E1S were suppressed markedly by vorozole, whereas levels of SHBG increased and LH and FSH fell significantly with tamoxifen. IGF-1 levels fell significantly with tamoxifen (P =.001) compared with the nonsignificant rise with vorozole. Twelve-week CTx values fell by 19% with tamoxifen (P =.006) and rose by 11% with vorozole (P =.15). CONCLUSION: The correlation with vorozole of Ki67 with volume and clinical response supports this as an intermediate marker. The nonsignificant effects on bone and lipid metabolism by the aromatase inhibitor may be important to consider for adjuvant and potential prevention strategies.     

Consultation planning to help breast cancer patients prepare for medical consultations: effect on communication and satisfaction for patients and physicians.

PURPOSE: To measure the prevalence of communication barriers between breast cancer patients and their physicians and to present the results of a study evaluating the impact of two visit preparation techniques on communication and satisfaction for breast cancer patients and their physicians. PATIENTS AND METHODS: We recruited 132 breast cancer patients from two outpatient cancer centers in a sequential, controlled trial. Ninety-four consented and completed the trial. Patients were assigned to one of two visit preparation interventions before their appointment with either a surgeon or a medical oncologist. In the control intervention, called Productive Listening, a researcher listened to and prompted patients to reflect on their experiences communicating with physicians. In the experimental intervention, called Consultation Planning, a researcher elicited questions and concerns, generated a printed agenda for the upcoming consultation, and engaged patients in techniques to improve communication with their physicians. Valid and reliable surveys measured communication barriers, satisfaction with the intervention, and patients' and physicians' satisfaction with the consultation. RESULTS: Sixty-four percent of the patients reported three or more communication barriers. Patients reported a significant reduction in communication barriers after both the intervention and the control session. Patients reported significantly higher satisfaction after the Consultation Planning sessions. Physicians reported significantly higher satisfaction with those patients who had participated in a Consultation Planning session. CONCLUSION: Visit preparation sessions help patients prepare for medical consultations and reduce barriers to communication. Consultation Planning sessions, in which a researcher solicited the patient's agenda, were more satisfying to patients and physicians than the Productive Listening sessions.     

Encounters between adolescents and general practice in Australia

Aim: To describe the nature of the encounters between adolescents and general practice in Australia. Methods: Data collected by the Bettering the Evaluation and Care of Health programme from 1998–2004 were analysed. Data for 10–14‐year‐old and 15–19‐year‐old males and females were compared with data for 25–29‐year‐olds. The outcome measures included: number of encounters compared with other age groups, reasons for encounter, problems managed, treatments prescribed and referrals made for key problems and types of consultations. Results: Adolescents have the lowest rate of encounter with general practice, compared with all other age groups. Respiratory, skin, musculoskeletal and unspecified (fever, injury, weakness) problems accounted for the great majority of reasons for encounter and problems managed. Management of mental health problems, preventive health care and health education were very infrequently managed problems. Standard surgery consultations were more common among adolescents than among young adults. Conclusions: Adolescents have a relatively low rate of encounter with general practice and the problems managed are primarily physical ailments. There is great scope to improve delivery of preventive health care and to increase management of mental health problems.