Georgios D Lianos

The role of heat shock proteins in cancer

Heat shock proteins (HSPs) are an evolutionary family of proteins that act as molecular chaperones. According to their size they have been classified into the following families; HSP90, HSP70, HSP60, HSP40 and HSP27. They prevent the formation of nonspecific protein aggregates and they assist proteins in the acquisition of their normal architecture. Moreover, HSPs are likely to have anti-apoptotic properties and are actively involved in various processes as tumor cell proliferation, invasion, metastases and death. Notably, these proteins have been reported to be significantly elevated in a plethora of human cancers. Their over-expression has been robustly associated with therapeutic resistance and poor survival. In this way, HSPs may have important therapeutic implications and they can be targeted by specific drugs. In this review, we discuss the influence of HSP27, HSP40, HSP60, HSP70 and HSP90 on human cancers. In addition, we report the existing scientific data on this issue with an effort to highlight the possible future implication of HSPs as tumor biomarkers or drug targets for improving prognosis and treatment of cancer patients around the world.

Potential of antibody–drug conjugates and novel therapeutics in breast cancer management

Progress in the treatment of cancer over the past decade has been slow. Targeting a mutated gene of an individual patient tumor, tumor-guided agents, and the first draft of the human genome sequence have created an overenthusiasm to achieve personalized medicine. However, we now know that this effort is misleading. Extreme interpatient and intratumor heterogeneity, scarce knowledge in how genome-wide mutational landscape and epigenetic changes affect transcriptional processes, gene expression, signaling transduction networks and cell regulation, and clinical assessment of temporary efficacy of targeted drugs explain the limitations of these currently available agents. Trastuzumab and a few other monoclonal antibodies or small-molecule tyrosine kinase inhibitors (TKIs) represent an exception to this rule. By blocking ligand-binding receptor in patients with human epidermal growth factor receptor 2 (HER2) amplification and overexpression, trastuzumab added to chemotherapy in HER2-positive patients has been proven to provide significant overall survival benefit in both metastatic and adjuvant settings. Lapatinib, a small-molecule dual inhibitor (TKI) of both HER2 and EGFR (epidermal growth factor receptor) pathways, has an antitumor activity translated into progression-free survival benefit in HER2-positive metastatic patients previously treated with a taxane, an anthracycline, and trastuzumab. Despite these advances, ~25% of patients with HER2-positive breast cancer experience recurrence in the adjuvant setting, while in the metastatic setting, median survival time is 25 months. In this review, we discuss the safety, efficacy, and limitations of the trastuzumab emtansine (T-DM1) conjugate in the treatment of HER2-positive metastatic breast cancer. We also highlight Phase III randomized trials, currently underway, using either the T-DM1 conjugate or various combinations of monoclonal antibodies and TKIs. Moreover, in contrast with all these agents developed on the basis of “central dogma” of simplified reductionist transcription and single gene–phenotype linear relationship, we summarize the emerging, amazing era of next-generation, transcriptional circuitry and intracellular signaling network-based drugs guided by the latest advances in genome science and dynamics of network biology.

Laparoscopic gastrectomy for gastric cancer: Current evidences

Nowadays, our understanding of gastric cancer has been improved. The major hope is to increase the survival rates of this aggressive, enigmatic and heterogeneous disease, especially in Western population. Over the past decades, conventional surgery has been the cornerstone of treatment for non metastatic gastric cancer patients. Adequate gastrectomy is recommended for at least T2-4a tumors, while T4b tumors require resection of involved structures. However, in the era of advanced technology, minimally invasive surgical approaches are in the top of the scientific interest. Notably, the laparoscopic approach for gastric cancer is a topic that remain controversial. In this review, we summarize the standard of care according to the current evidences and we provide the latest scientific information assessing safety and efficacy of laparoscopic gastrectomy for gastric cancer.

Quality of Life After Gastrectomy for Adenocarcinoma: A Prospective Cohort Study.

To the Editor: We read with extreme interest the innovative article published by Karanicolas et al about the quality of life after distal gastrectomy, proximal gastrectomy, and total gastrectomy. These colleagues have undoubtedly given important contributions to scientific literature in this surgical field and this article shows new results that advance our understanding in gastric surgery. We would like to offer our additional remark from a prospective point of view, pointing out some important elements to consider. The authors are to be commended for their aim to conduct a prospective cohort study to assess the impact of surgical gastric resection on the quality of life of a large

Continuous intraoperative neuromonitoring in thyroid surgery: Safety analysis of 400 consecutive electrode probe placements with standardized procedures

Continuous intraoperative neuromonitoring (C‐IONM) is a new technology and it is appropriate to analyze its safety.

Difluoromethylornithine in cancer: new advances

Difluoromethylornithine (DFMO; eflornithine) is an irreversible suicide inhibitor of the enzyme ornithine decarboxylase which is involved in polyamine synthesis. Polyamines are important for cell survival, thus DFMO was studied as an anticancer agent and as a chemoprevention agent. DFMO exhibited mainly cytostatic activity and had single agent efficacy as well as activity in combination with other chemotherapeutic drugs for some cancers and leukemias. Herewith, we summarize the current knowledge of the anticancer and chemopreventive properties of DFMO and assess the status of clinical trials.

Surgical management of hydatid liver disease

BACKGROUND large retrospective clinical study describing the long-term experience of a single center in the surgical management of liver echinococcosis in an endemic area. METHODS 232 patients were operated for liver hydatid disease between 1978 and 2012. Seventy-three patients (Group A) underwent a radical procedure (total pericystectomy or hepatectomy), while 145 (Group B) were treated with a more conservative method (partial cystectomy, with external drainage, omentoplasty or capitonnage) and 14 (Group C) received a combination of total and partial cystectomies. Morbidity, mortality, post-operative complications and recurrence rates in the long-term setting were retrospectively evaluated. RESULTS Group A patients were treated with zero mortality and a morbidity rate of 10.95%. No recurrence was documented. In Group B, mortality reached 2.76%, (p = 0.153 compared to Group A) morbidity 24.13% (p = 0.021) and there were 10 cases of relapse (6.9%) at three-year complete follow-up (p = 0.989). Extrahepatic sites of disease were not uncommon. DISCUSSION radical surgical procedures were better tolerated by patients and yielded better results in terms of recurrence rates.

Admission glucose and coagulopathy occurrence in patients with traumatic brain injury.

Abstract Introduction: Coagulopathy after traumatic brain injury (TBI) is a frequent event and is associated with patients’ prognosis. TBI is also associated with a stress response that includes hyperglycemia. This study investigated if coagulopathy occurrence is associated with admission blood glucose levels in patients with TBI. Methods: This study retrospectively evaluated patients with TBI who were admitted to a neurosurgical department over a 4-year period. Coagulopathy was defined as an aPTT >40 seconds and/or INR >1.2 and/or a platelet count <120*109 per litre. Results: One-hundred and forty-nine patients were included in the study. Thirty-four patients developed coagulopathy. Patients with coagulopathy had significantly lower haemoglobin levels, increased INR and increased aPTT. Patients with severe TBI had more frequent coagulopathy. Patients with severe TBI had significant higher serum glucose levels compared to patients with mild TBI. Using ROC curves it was found that a serum glucose of 151 mg dl−1 was the threshold for the discrimination of patients that developed coagulopathy. Logistic regression analysis revealed that serum glucose greater than 151 mg dl−1 and haemoglobin levels lower than 12.4 mg dL−1 were significantly associated with coagulopathy occurrence. Conclusion: Coagulopathy frequently occur after TBI. Patients with lower GCS score and lower haemoglobin levels and increased blood glucose levels at admission are at greater risk.

BMI and lymph node ratio may predict clinical outcomes of gastric cancer.

AIM BMI and the lymph node (LN) ratio can affect short- and long-term outcomes of patients with gastric cancer. PATIENTS & METHODS This study includes 104 consecutive patients with gastric adenocarcinoma who underwent curative gastrectomy divided in two groups: overweight group (group A) and normal weight group (group B). RESULTS We found that 53.4% of our patients were overweight (group A). The overall rate of postoperative complications was 16.3%, while mortality was 1%. Statistical analyses revealed that postoperative morbidity was significantly higher in group A (p < 0.05). Long-term survival was significantly higher in group B. Cox regression showed a statistically significant correlation between higher BMI and poor long-term survival after curative gastrectomy. Multivariate analysis has identified age and the LN ratios as independent prognostic factors of survival. CONCLUSION In this retrospective analysis, BMI and LN ratio were independently associated with survival in patients with gastric cancer. Further studies are needed to confirm our findings.

Dynamic sequencing of circulating tumor DNA: novel noninvasive cancer biomarker

Despite high-throughput technological and computational advances, progress in discovering robust biomarkers for personalized monitoring of cancer patients with potentially curable or metastatic disease is modest. Genome sequencing of ‘fluid’ biopsy may be a novel robust biomarker in monitoring cancer patients after treatment. In this article, we highlight the proof of principle for circulating tumor DNA (ctDNA) sequencing provided by a recent study [1] and the challenges for clinical implementation. If confirmed, this new method will change clinical trials’ design. The combination of this new technique for ctDNA detection in plasma and the subsequent next-generation sequencing (NGS) can provide a dual advantage. First, it can early predict recurrence or disease progression before this event occurs. Second, this ctDNA-NGS-based approach can guide a new therapeutic decision selecting drug(s) to disrupt cellular pathways deregulated by initial therapy-resistant emerging mutations and clonal selection rather than primary tumor genetic analysis.