19^th European Pathology Congress September 20-21, 2021 Paris, France

Biography:

Abstract:

Diabetes mellitus has been related to testicular damage in men. Glutathione (GSH) is a nonenzymatic antioxidant that defends lipids, proteins, and nucleic acids against oxidative stress. This study was conducted to investigate the effects of exogenous GSH treatment on the morphology of seminiferous tubules, as well as Bax/Bcl-2 gene and protein expressions in the testes of diabetic mice. Twenty-four male C57BL/6 mice were divided into four groups (n=6). Group A was non-diabetic control, while Group B was non-diabetic GSH-treated mice. Group C was diabetic control mice and Group D was diabetic GSH-treated mice. Diabetes was induced by intraperitoneal injection of 50 mg kg^-1 streptozotocin (STZ). Exogenous GSH at 15 mg kg^-1 body weight was intraperitoneally administered to the Groups B and D once a week, for six weeks. The mice were weighed, euthanized, and their testes excised. The diameter of seminiferous tubules was assessed using haematoxylin and eosin staining, and apoptotic cells were observed using TUNEL fluorescent assay. Gene and protein expression levels of Bcl-2 and Bax in response to GSH treatment were measured using quantitative real-time PCR (RT-qPCR) and ELISA protein quantification. Data were analysed using one-way ANOVA. Group C showed significantly impaired testicular morphology, with shorter seminiferous tubule diameter and larger seminiferous lumen diameter compared to Group A (P<0.05). However, significant increase and decrease in tubular and luminal diameters were observed in Group D, relative to Group C, respectively. The significant improvements, however, did not have a substantial impact on the Johnsen score, but the findings were supported by the apoptotic index (AI) obtained from the TUNEL assay. The AI in Group D was reduced compared to Group C (P<0.05). It was noted that Bcl-2 gene and protein expressions increased, while Bax gene and protein expressions decreased, in comparison to Group C (P<0.05), resulting in a lower Bax/Bcl2 ratio in Group D. Improved testicular morphology and the Bax/Bcl-2 ratio is an early indication of the protective role exogenous GSH plays in protecting testicular morphology from the effects of untreated diabetes or diabetic complications. The current findings indicate that there are variety of mechanisms that may contribute to and likely interfere with impaired testicular function in diabetic mice, some of which may be addressed with exogenous GSH.

Biography:

Michael Retsky received PhD in experimental physics from University of Chicago in 1974. While working at Hewlett-Packard in Colorado Springs in 1982, a friend started an informal cancer research project since his wife was being treated for cancer. Over the next years, Retsky made a career change into cancer research. His first paper in oncology (Cancer Research 1984) predicted that tumor growth included periods of dormancy. He eventually became Prof of Biology at Univ of Colorado and later on staff of Judah Folkman at Harvard.

Retsky was diagnosed with Stage IIIc colon cancer in 1994. Based on his knowledge of tumor kinetics he used low-dose, long-term chemotherapy instead of maximum tolerated chemotherapy.

Abstract:

My colleagues and I have been studying an anomalous relapse pattern in breast cancer. This project started in 1993 when data from Italy and UK showed that 50 to 80% of all relapses in patients treated only with surgery occurred in an early wave of relapses in the first 3 years post-surgery.  We proposed a reasonable explanation. It appears that the surgery to remove a primary tumor causes systemic inflammation for a week. During that time, dormant single malignant cells and avascular deposits escape from dormancy and appear as relapses within 3 years. The multi-national authors of our reports include medical oncologists, surgeons, anaesthesiologists, physicists, and other scientists from several fields. A potential solution seems to exist based on our analysis. That therapy is the common inexpensive analgesic ketorolac administered as iv at the time of surgery and perhaps as oral drug for a few days after surgery. We edited a book and published a number of papers including one recently (1).  Two animal models support our findings (2,3). Another paper suggests a way to prevent some late relapses (4) and a second retrospective clinical trial was reported (5).  

Biography:

Michael Retsky received PhD in experimental physics from University of Chicago in 1974. While working at Hewlett-Packard in Colorado Springs in 1982, a friend started an informal cancer research project since his wife was being treated for cancer. Over the next years, Retsky made a career change into cancer research. His first paper in oncology (Cancer Research 1984) predicted that tumor growth included periods of dormancy. He eventually became Prof of Biology at Univ of Colorado and later on staff of Judah Folkman at Harvard.

Retsky was diagnosed with Stage IIIc colon cancer in 1994. Based on his knowledge of tumor kinetics he used low-dose, long-term chemotherapy instead of maximum tolerated chemotherapy.

Abstract:

My colleagues and I have been studying an anomalous relapse pattern in breast cancer. This project started in 1993 when data from Italy and UK showed that 50 to 80% of all relapses in patients treated only with surgery occurred in an early wave of relapses in the first 3 years post-surgery.  We proposed a reasonable explanation. It appears that the surgery to remove a primary tumor causes systemic inflammation for a week. During that time, dormant single malignant cells and avascular deposits escape from dormancy and appear as relapses within 3 years. The multi-national authors of our reports include medical oncologists, surgeons, anaesthesiologists, physicists, and other scientists from several fields. A potential solution seems to exist based on our analysis. That therapy is the common inexpensive analgesic ketorolac administered as iv at the time of surgery and perhaps as oral drug for a few days after surgery. We edited a book and published a number of papers including one recently (1).  Two animal models support our findings (2,3). Another paper suggests a way to prevent some late relapses (4) and a second retrospective clinical trial was reported (5).  

Biography:

Bogdan Czerniak, MD, PhD, is a Professor of Pathology in the Department of Pathology at The University of Texas MD Anderson Cancer Center, Houston, Texas. He received his MD, PhD from the Pomeranian Medical Academy in Szczecin, Poland in 1973 and 1976 respectively. In 1982- 1984 he was an NIH Fellow at Montefiore Medical Center in New York. Since 1993, he has been working at The University of Texas MD Anderson Cancer Center. His laboratory conducts research on mechanisms of bladder cancer development with a focus of early incipient events of urothelial carcinogenesis.

Abstract:

Identifying the mechanisms of cancer initiation is essential for the development of early detection and prevention strategies to intercept carcinogenesis in its occult phases before it progresses to a clinically aggressive and incurable disease. We used bladder cancer as a model for such studies as the simple anatomy of the organ facilitates the mapping of precursor lesions and field effects in microscopically intact adjacent mucosa on the scale of the entire organ. We performed whole-organ mapping of molecular changes in the evolution of human bladder cancer by multi-platform genomic analysis. This approach identified over 100 dysregulated pathways affecting immunity, tissue differentiation, and transformation as early events of bladder carcinogenesis. Extensive dysregulations of interleukin signalling combined with aberrant methylation of HOX genes in a background of multiple activated oncogenic pathways were the dominant features of the field effects. There were three types of mutations based on their geographic distribution and frequencies of variant alleles. The most common were low-frequency mutations restricted to individual mucosal samples. Two additional types of mutations were associated with clonal expansion. The first exhibited low mutational frequencies and the second increased in their frequencies with disease progression. Time modeling showed that bladder cancer evolves over 10-15 years and its development can be divided into dormant and progressive phases. The progressive phase lasted 1-2 years and was driven by a specific subset of mutations involving genes with high proliferative advantage. This is the first comprehensive characterization of bladder cancer evolving from field effects on the whole-organ scale.