Thymoglobulin versus alemtuzumab versus basiliximab kidney transplantation from donors after circulatory death

Introduction 3C, a study comparing alemtuzumab versus basiliximab induction immunosuppression in kidney transplants has shown lower acute rejection rate with alemtuzumab but same graft survival. Aim of the current study is to examine the effect of induction immunosuppression (thymoglobulin, alemtuzumab, basiliximab) on the outcome of kidneys after circulatory death (DCD). Methods Data of the 274 DCD patients of the 3C obtained from the sponsor was compounded with the 140 DCD patients who received thymoglobulin in a single centre with the same entry criteria as the 3C, giving 414 patients on three induction regimes. Results There were more male donors (p<0.05) and HLA-DR mismatched patients in the thymoglobulin group (p<0.001). Death-censored graft survival at 6-months was 98.6% in the thymoglobulin, 95.5% in alemtuzumab (p=0.08) and 95.7% in basiliximab group (p=0.09), and at 2-years 97.9% vs. 94.8% (p=0.13, HR 2.8, CI 0.7-10.9), vs. 94.3% (p=0.06, HR 3.5, 95% CI 0.9-13.6) respectively. 2-year overall graft survival was 95% in the thymoglobulin vs. 88% in alemtuzumab (unadjusted p=0.038, adjusted HR 2.4, 95% CI 0.99-5.9) and 91.4% in the basiliximab group (p=0.21). 2-years patient survival was numerically less in the alemtuzumab compared to thymoglobulin group (91.8% vs 97.1%, p=0.052, HR 2.90 95% CI 0.93-9.2). Acute rejection was 17% in the basiliximab, 4.3% in the thymoglobulin and 6% in the alemtuzumab group (p<0.001). Conclusion In DCD transplants, thymoglobulin induction may provide advantage over alemtuzumab in patient survival and the same advantage as alemtuzumab over basiliximab in terms of acute rejection. Differing maintenance immunosuppression may contribute to the difference seen

Human Gyrovirus Apoptin shows a similar subcellular distribution pattern and apoptosis induction as the chicken anaemia virus derived VP3/Apoptin

The chicken anaemia virus-derived protein Apoptin/VP3 (CAV-Apoptin) has the important ability to induce tumour-selective apoptosis in a variety of human cancer cells. Recently the first human Gyrovirus (HGyV) was isolated from a human skin swab. It shows significant structural and organisational resemblance to CAV and encodes a homologue of CAV-Apoptin/VP3. Using overlapping primers we constructed a synthetic human Gyrovirus Apoptin (HGyV-Apoptin) fused to green fluorescent protein in order to compare its apoptotic function in various human cancer cell lines to CAV-Apoptin. HGyV-Apoptin displayed a similar subcellular expression pattern as observed for CAV-Apoptin, marked by translocation to the nucleus of cancer cells, although it is predominantly located in the cytosol of normal human cells. Furthermore, expression of either HGyV-Apoptin or CAV-Apoptin in several cancer cell lines triggered apoptosis at comparable levels. These findings indicate a potential anti-cancer role for HGyV-Apoptin

A phase II study of single-agent gefitinib as first-line therapy in patients with stage IV non-small-cell lung cancer

The aim of this study was to evaluate the efficacy and tolerability of gefitinib (‘IRESSA') in Japanese patients with previously untreated stage IV non-small-cell lung cancer (NSCLC). This was a multi-institutional phase II study. Thirty-four patients with previously untreated stage IV NSCLC were enrolled between May 2003 and September 2004. Gefitinib was administered orally 250 mg once a day and was continued until there was either disease progression or severe toxicity. Objective tumour response rate was 26.5% (95% confidence interval, 11.7–41.3%). Adverse events were generally mild (National Cancer Institute-Common Toxicity Criteria grade 1 or 2) and consisted mainly of skin rash, fatigue and liver dysfunction. No pulmonary toxicity was observed. The global health status revealed that there was no change in quality of life during the study. This study found that single-agent gefitinib is active and well tolerated in chemonaive Japanese patients with advanced NSCLC

Patients’ experience of recurrent/metastatic head and neck squamous cell carcinoma and their perspective on the EORTC QLQC30 and QLQ-H&amp;N35 questionnaires: a qualitative study

Abstract Background Head and neck squamous cell carcinoma (HNSCC) and its associated treatments may affect all aspects of patients’ health-related quality of life (HRQoL). Although the EORTC QLQ-H&N35 is regularly administered to patients with HNSCC, there is a paucity of studies re-assessing the conceptual relevance of this patient-reported outcome (PRO) measure from a patient perspective. Furthermore, the content validity of the EORTC QLQ-C30 has not been widely documented in patients with recurrent and/or metastatic HNSCC. The objectives of this study were to understand patients’ experiences of recurrent/metastatic HNSCC and its treatments, and to evaluate the conceptual relevance and acceptability of the EORTC QLQ-C30 and QLQ-H&N35 from a patient perspective for use in clinical trials. Methods A literature review and clinician interviews were conducted to inform in-depth semi-structured telephone interviews with US patients who had received treatment for recurrent and/or metastatic HNSCC in the preceding 12 months. Interview transcripts were analysed thematically using ATLAS.ti v7; patient quotes were coded to identify concepts and themes to develop a conceptual model of HNSCC experience. Results Fourteen patients were interviewed (71% male, aged 35–84 years). Patients reported few symptoms pre-diagnosis including neck lump/swelling (n = 7/14, 50%) and/or difficulty swallowing (n = 3/14, 21%). Treatments generally comprised surgery and chemotherapy and/or radiotherapy. A number of side effects from all treatments were reported. Numbness, difficulty speaking and pain were the most reported side effects of surgery (n = 4/8, 50%); weight loss and fatigue were the most reported side effects of chemotherapy and/or radiotherapy (n = 8/13, 61%). All side effects negatively impacted patients’ HRQoL. Patients generally found the QLQ-C30 and QLQ H&N35 content to be understandable and conceptually relevant; excessive mucous production and neuropathic symptoms were among the suggested additions. Conclusions HNSCC and its diverse symptoms and treatments have a negative impact on many aspects of patients’ lives. A number of reported symptoms including difficulty speaking and swallowing, localised pain and fatigue may be important for treatment benefit evaluation in clinical trials from a patient perspective. The QLQ-C30 and QLQ-H&N35 are generally relevant and suitable for use in clinical trials. However, some items could be amended/added to ensure conceptual comprehensiveness of these measures

Expression Profiling of CYP1B1 in Oral Squamous Cell Carcinoma: Counterintuitive Downregulation in Tumors

Oral Squamous Cell Carcinoma (OSCC) has a very flagitious treatment regime. A prodrug approach is thought to aid in targeting chemotherapy. CYP1B1, a member of cytochrome P450 family, has been implicated in chemical carcinogenesis. There exists a general accordance that this protein is overexpressed in a variety of cancers, making it an ideal candidate for a prodrug therapy. The activation of the prodrug facilitated by CYP1B1 would enable the targeting of chemotherapy to tumor tissues in which CYP1B1 is specifically overexpressed as a result reducing the non-specific side effects that the current chemotherapy elicits. This study was aimed at validating the use of CYP1B1 as a target for the prodrug therapy in OSCC. The expression profile of CYP1B1 was analysed in a panel of 51 OSCC tumors, their corresponding normal tissues, an epithelial dysplasia lesion and its matched normal tissue by qRT-PCR, Western blotting and Immunohistochemistry. CYP1B1 was found to be downregulated in 77.78% (28/36) tumor tissues in comparison to their corresponding normal tissues as well as in the epithelial dysplasia lesion compared to its matched normal tissue at the transcriptional level, and in 92.86% (26/28) of tumor tissues at the protein level. This report therefore clearly demonstrates the downregulation of CYP1B1 at the transcriptional and translational levels in tumor tissues in comparison to their corresponding normal tissues. These observations indicate that caution should be observed as this therapy may not be applicable universally to all cancers and also suggest the possibility of a prophylactic therapy for oral cancer

Twist and snai1 expression in pharyngeal squamous cell carcinoma stroma is related to cancer progression

<p>Abstract</p> <p>Background</p> <p>Epithelial-mesenchymal transition (EMT) is a crucial process in tumorigenesis since tumor cells attain fibroblast-like features enabling them to invade to surrounding tissue. Two transcription factors, <it>TWIST </it>and <it>SNAI1</it>, are fundamental in regulating EMT.</p> <p>Methods</p> <p>Immunohistochemistry was used to study the expression of TWIST and SNAI1 in 109 pharyngeal squamous cell carcinomas.</p> <p>Results</p> <p>Tumors with intense stromal staining of TWIST relapsed more frequently (p = 0.04). Tumors with both positive TWIST and SNAI1 immunoreactivity in the stroma were at least Stage II (p = 0.05) and located more often in hypopharynx (p = 0.035). Tumors with negative immunostaining of TWIST and SNAI1 in the stromal compartment were smaller (T1-2) (p = 0.008), less advanced (SI-II) (p = 0.031) and located more often in the oropharynx (p = 0.007). Patients with negative SNAI1 and TWIST immunostaining in tumor stroma had a better 5-year disease-specific and overall survival (p = 0.037 and p = 0.014 respectively).</p> <p>Conclusion</p> <p>TWIST and SNAI1 expression in stromal cells is associated with clinical and histopathological characteristics that indicate progressive disease. Negative expression of these EMT-promoting transcription factors predicts a better outcome.</p

Associations between XPD Asp312Asn Polymorphism and Risk of Head and Neck Cancer: A Meta-Analysis Based on 7,122 Subjects

Background: To investigate the association between XPD Asp312Asn polymorphism and head and neck cancer risk through this meta-analysis. Methods: We performed a meta-analysis of 9 published case-control studies including 2,670 patients with head and neck cancer and 4,452 controls. An odds ratio (OR) with a 95 % confidence interval (CI) was applied to assess the association between XPD Asp312Asn polymorphism and head and neck cancer risk. Results: Overall, no significant association between XPD Asp312Asn polymorphism and head and neck cancer risk was found in this meta-analysis (Asn/Asn vs. Asp/Asp: OR = 0.95, 95%CI = 0.80–1.13, P = 0.550, Pheterogeneity = 0.126; Asp/Asn vs. Asp/Asp: OR = 1.11, 95%CI = 0.99–1.24, P = 0.065, P heterogeneity = 0.663; Asn/Asn+Asp/Asn vs. Asp/Asp: OR = 1.07, 95%CI = 0.97–1.19, P = 0.189, P heterogeneity = 0.627; Asn/Asn vs. Asp/Asp+Asp/Asn: OR = 0.87, 95%CI = 0.68–1.10, P = 0.243, Pheterogeneity = 0.089). In the subgroup analysis by HWE, ethnicity, and study design, there was still no significant association detected in all genetic models. Conclusions: This meta-analysis demonstrates that XPD Asp312Asn polymorphism may not be a risk factor for developing head and neck cancer

A review of clinical trials of cetuximab combined with radiotherapy for non-small cell lung cancer

Treatment of non-small cell lung cancer (NSCLC) is challenging in many ways. One of the problems is disappointing local control rates in larger volume disease. Moreover, the likelihood of both nodal and distant spread increases with primary tumour (T-) stage. Many patients are elderly and have considerable comorbidity. Therefore, aggressive combined modality treatment might be contraindicated or poorly tolerated. In many cases with larger tumour volume, sufficiently high radiation doses can not be administered because the tolerance of surrounding normal tissues must be respected. Under such circumstances, simultaneous administration of radiosensitizing agents, which increase tumour cell kill, might improve the therapeutic ratio. If such agents have a favourable toxicity profile, even elderly patients might tolerate concomitant treatment. Based on sound preclinical evidence, several relatively small studies have examined radiotherapy (RT) with cetuximab in stage III NSCLC. Three different strategies were pursued: 1) RT plus cetuximab (2 studies), 2) induction chemotherapy followed by RT plus cetuximab (2 studies) and 3) concomitant RT and chemotherapy plus cetuximab (2 studies). Radiation doses were limited to 60-70 Gy. As a result of study design, in particular lack of randomised comparison between cetuximab and no cetuximab, the efficacy results are difficult to interpret. However, strategy 1) and 3) appear more promising than induction chemotherapy followed by RT and cetuximab. Toxicity and adverse events were more common when concomitant chemotherapy was given. Nevertheless, combined treatment appears feasible. The role of consolidation cetuximab after RT is uncertain. A large randomised phase III study of combined RT, chemotherapy and cetuximab has been initiated

A study of head and neck cancer treatment and survival among indigenous and non-indigenous people in Queensland, Australia, 1998 to 2004

Background: Overall, Indigenous Australians with cancer are diagnosed with more advanced disease, receive less cancer treatment and have poorer cancer survival than non-Indigenous Australians. The prognosis for Indigenous people with specific cancers varies however, and their prognosis for cancers of the head and neck is largely unknown. We therefore have compared clinical characteristics, treatment and survival between Indigenous and non-Indigenous people diagnosed with head and neck cancer in Queensland, Australia. Methods: Rates were based on a cohort of Indigenous people (n = 67), treated in public hospitals between 1998 and 2004 and frequency-matched on age and location to non-Indigenous cases (n = 62) also treated in the public health system. Data were obtained from hospital records and the National Death Index. We used Pearson's Chi-squared analysis to compare categorical data (proportions) and Cox proportional hazard models to assess survival differences.Results: There were no significant differences in socioeconomic status, stage at diagnosis or number and severity of comorbidities between Indigenous and non-Indigenous patients, although Indigenous patients were more likely to have diabetes. Indigenous people were significantly less likely to receive any cancer treatment (75% vs. 95%, P = 0.005) and, when cancer stage, socioeconomic status, comorbidities and cancer treatment were taken into account, they experienced greater risk of death from head and neck cancer (HR 1.88, 1.10, 3.22) and from all other causes (HR 5.83, 95% CI 1.09, 31.04).Conclusion: These findings show for the first time that Indigenous Australians with head and neck cancer receive less cancer treatment and suggest survival disparity could be reduced if treatment uptake was improved. There is a need for a greater understanding of the reasons for such treatment and survival disparities, including the impact of the poorer overall health on cancer outcomes for Indigenous Australians