Bad expression influences time to androgen escape in prostate cancer

<b>OBJECTIVE</b>: To assess the role of selected downstream Bcl-2 family members (Bad, Bax, Bcl-2 and Bcl-xL) in the development of androgen-independent prostate cancer (AIPC), as androgen-deprivation therapy is the treatment of choice in advanced prostate cancer, yet patients generally relapse and progress to an AI state within 18–24 months. <b>PATIENTS, MATERIALS AND METHODS</b>: The patient cohort was established by retrospectively selecting patients with prostate cancer who had an initial response to androgen-deprivation therapy, but subsequently relapsed with AIPC. In all, 58 patients with prostate cancer were included with matched androgen-dependent (AD) and AI prostate tumours available for immunohistochemical analysis; two independent observers using a weighted-histoscore method scored the staining. Changes in Bad, Bax, Bcl-2 and Bcl-xL expression during transition to AIPC were evaluated and then correlated to known clinical variables. <b>RESULTS</b>: High Bad expression in AD tumours was associated with an increased time to biochemical relapse (<i>P</i> = 0.007) and a trend towards improved overall survival (<i>P</i> = 0.053). There were also trends towards a decrease in Bad (<i>P</i> = 0.068) and Bax (<i>P</i> = 0.055) expression with progression to AIPC. There were no significant results for Bcl-2 or Bcl-xL. <b>CONCLUSION</b>: There is evidence to suggest that Bad expression levels at diagnosis influence time to biochemical relapse and overall survival, and that levels of pro-apoptotic proteins Bad and Bax fall during AIPC development. Bad might therefore represent a possible positive prognostic marker and potential therapeutic target for AIPC in the future

Sunitinib in metastatic renal cell carcinoma: The pharmacological basis of the alternative 2/1 schedule

No abstract availabl

Protein kinase inhibitors in the treatment of renal cell carcinoma: sorafenib

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Bone health management in the continuum of prostate cancer disease: a review of the evidence with an expert panel opinion

Bone health impairment is a frequent detrimental consequence of the high bone tropism of prostate cancer (PCa) cells. It is further worsened by administration of androgen-deprivation therapy (ADT), the current standard of care in the management of advanced PCa, through a rapid and dramatic increase in bone turnover and body mass changes. As a result, patients may experience substantial pain and poor quality of life (QoL) and have an increased risk of death. Notwithstanding the importance of this issue, however, bone health preservation is not yet a widespread clinical goal in daily practice.To address this urgent unmet need, following a thorough discussion of available data and sharing of their clinical practice experience, a panel of Italian experts in the field of bone health and metabolism formulated a number of practical advices for optimising the monitoring and treatment of bone health in men undergoing ADT during all phases of the disease. The rationale behind the venture was to raise awareness on the importance of bone preservation in this complex setting, while providing an instrument to support physicians and facilitate the management of bone health.Current evidence regarding the effects on bone health of ADT, of novel hormone therapies (which improve progression delay, pain control and QoL while consistently carrying the risk of non-pathological fractures in both non-metastatic and metastatic PCa) and of bone turnover inhibitors (whose use is frequently suboptimal) is reviewed. Finally, the expert opinion to optimise bone health preservation is given

A protocol for cooperation to establish an International Gastric Cancer Unit (IGCU)

The following text shows the terms of a protocol for cooperation recently signed between the Department of Digestive Surgery - St. Mary’s Hospital (Terni, Italy; hereinafter “SMH”), the Department of Surgical Sciences - “La Sapienza” University (Rome, Italy; hereinafter “SUR”) and the Department of Gastric Surgery - Fujian Medical University Union Hospital (Fuzhou, Fujian Province, PRC; hereinafter “FMU”)

A protocol for cooperation to establish an International Gastric Cancer Unit (IGCU)

The following text shows the terms of a protocol for cooperation recently signed between The Department of Digestive Surgery - St. Mary’s Hospital (Terni, Italy; hereinafter “SMH”), the Department of Surgical Sciences - “La Sapienza” University (Rome, Italy; hereinafter “SUR”) and the Department of Gastric Surgery - Fujian Medical University Union Hospital (Fuzhou, Fujian Province, PRC; hereinafter “FMU”)

Comparing comparators: A look at control arms in kidney cancer studies over the years

In the past decade, an increasing number of frequently positive randomised clinical trials have been completed, allowing new consideration of the present therapeutic armamentarium for advanced renal cell carcinoma. These studies were predominantly designed to compare the experimental drugs with 1 of 2 active control arms: interferon alpha-2a or sorafenib. Different from expectations, the final results of some of these studies were not in line with the predictions, and the reasons have not been fully investigated. Consequently, there is a great need for careful analysis of the studies carried out so far, chiefly the role and validity of the control arms. In this regard, the examination of patient baseline characteristics and other factors of potential interest seems fundamental for a correct analysis of the results of these trials and consequent optimal use of the available targeted agents

CXC and CC chemokines as angiogenic modulators in nonhaematological tumors.

Chemokines are a superfamily of structurally homologous heparin-binding proteins that includes potent inducers and inhibitors of angiogenesis. The imbalance between angiogenic and angiostatic chemokine activities can lead to abnormalities, such as chronic inflammation, dysplastic transformation, and even tumor development and spreading. In this review, we summarize the current literature regarding the role of chemokines as modulators of tumor angiogenesis and their potential role as therapeutic targets in patients with nonhaematological tumors

Enhanced Recovery After Surgery (ERAS) Protocol for Gastrectomy: A Tailored Program Developed at a Gastric Cancer Unit

Background Planning for and managing patients who follow multidisciplinary paths allow institutions to provide better care administration; greater collaboration among medical staff, patients, and their relatives; better patients education; reduced possible complications related to surgery and hospital stay; and increased patient adherence to the proposed treatments due to better information. The ERAS Society’s guidelines align in this direction, and many institutions are now looking to apply the suggestions contained in its items. This effort is especially important in surgical oncology. In this work, we report the experience of our center in developing tailored guidelines for patients undergoing gastrectomy based on evidence from the literature and adapted to address the availability of personnel and equipment in our institute. Methods A permanent institutional working group was established at St. Mary’s Hospital. Evidence‐based comprehensive research was conducted to find optimal perioperative care management for patients undergoing gastrectomy. Evidence and recommendations were thoroughly evaluated and considered together with the items from the ERAS Society’s guidelines. Results A complete patient pathway has been established from the first outpatient visit to discharge. All ERAS items were considered and adapted to our hospital’s care environment. Education, nutrition, anesthesiologist care, surgical approach, and ward organization are the main points of strength highlighted in the present work. Conclusion This proposed institutional evidence‐based protocol show comprehensive management for patients with gastric cancer eligible for enhanced surgical pathways

Gastrectomy for stage IV gastric cancer. A comparison of different treatment strategies from the SEER database

In the West, more than one third of newly diagnosed subjects show metastatic disease in gastric cancer (mGC) with few care options available. Gastrectomy has recently become a subject of debate, with some evidence showing advantages in survival beyond the sole purpose of treatment tumor-related complications. We investigated the survival benefit of different strategies in mGC patients, focusing on the role and timing of gastrectomy. Data were extracted from the SEER database. Groups were determined according to whether patients received gastrectomy, chemotherapy, supportive care. Patients receiving a multimodality treatment were further divided according to timing of surgery, whether performed before (primary gastrectomy, PG) or after chemotherapy (secondary gastrectomy, SG). 16,596 patients were included. Median OS was significantly higher (p<0.001) in the SG (15months) than in the PG (13months), gastrectomy alone (6months), and chemotherapy (7months) groups. In the multivariate analysis, SG showed better OS (HR=0.22, 95%CI=0.18-0.26, p<0.001) than PG (HR=0.25, 95%CI=0.23-0.28, p<0.001), gastrectomy (HR=0.40, 95%CI=0.36-0.44, p<0.001), and chemotherapy (HR=0.42, 95%CI=0.4-0.44, p<0.001). The survival benefits persisted even after the PSM analysis. This study shows survival advantages of gastrectomy as multimodality strategy after chemotherapy. In selected patients, SG can be proposed to improve the management of stage IV disease