Clinical Oncology and Molecular Diagnostics

Michael Retsky (PhD in Physics from University of Chicago) made a career change to cancer research thirty years ago. He is Research Associate at Harvard TH Chan School of Public Health and Honorary Reader at University College London. He was on Judah Folkman’s staff at Harvard Medical School for 12 years. Retsky is Editor of a Springer-Nature book on the breast cancer project published July 2017. After diagnosis of stage IIIc colon cancer in 1994, he was the first person to use what is now called metronomic adjuvant chemotherapy. He is a founder and for 10 years was on the Board of Directors of the Colon Cancer Alliance. He has published more than 70 papers in physics and cancer.

A bimodal pattern of hazard of relapse among early stage breast cancer patients has been identified in multiple databases from US, Europe and Asia. We are studying these data to determine if this can lead to new ideas on how to prevent relapse in breast cancer. Using computer simulation and access to a very high-quality database from Milan for patients treated with mastectomy only, we proposed that relapses within 3 years of surgery are stimulated somehow by the surgical procedure. Most relapses in breast cancer are in this early category. Retrospective data from a Brussels anesthesiology group suggests a plausible mechanism. Use of ketorolac, a common NSAID analgesic used in surgery was associated with far superior disease-free survival in the first 5 years after surgery. The expected prominent early relapse events in months 9-18 are reduced 5-fold. Transient systemic inflammation accompanying surgery (identified by IL-6 in serum) could facilitate angiogenesis of dormant micro metastases, proliferation of dormant single cells, and seeding of circulating cancer stem cells (perhaps in part released from bone marrow) resulting in early relapse and could have been effectively blocked by the perioperative anti-inflammatory agent. If this observation holds up to further scrutiny, it could mean that the simple use of this safe, inexpensive and effective anti-inflammatory agent at surgery might eliminate early relapses. We suggest this would be most effective for triple negative breast cancer and be especially valuable in low and middle-income countries. Similar bimodal patterns have been identified in other cancers suggesting a general effect. Based on the writings of Galen and Celsus, metastatic stimulation after surgery was known 2000 years ago.\r\n\r\n\r\nwritings of Galen and Celsus, such an effect was known to premodern physicians 2000 years ago.\r\n

Dr. Ebru Dundar Yenilmez, PhD-Medical Biochemistry, now is an Assistant Lecturer and Specialist of Medical Biochemistry, General Manager Assistant of the Prenatal Diagnosis Laboratory of the Department. Member of Turkish Biochemistry Society, International Federation of Clinical Chemistry (IFCC), Europan Society of Human Genetic (ESHG). She got her B Sc in Biology, M Sc in Medical Biochemistry, Specialist in Medical Biochemistry, Medicine doctor’s degree (Ph.D.) at Medicine Faculty of Cukurova University. Dr. Ebru Dündar Yenilmez researches focus on the molecular basis of the inherited blood disorders (Thalassemias, sickle cell anemias), cystic fibrosis, hemophilia’s, congenital adrenal hyperplasia etc., gene expression, donor chimerism monitoring of pediatric hematology/oncology patients. Now is specialist of the Prenatal Diagnosis Laboratory of Hemoglobinopathies

Hematopoietic stem cell transplantation (HSCT) is becoming an increasingly important approach to treatment children and adults with different malignant and nonmalignant diseases. Donor chimerism analysis has become a routine method for the following the newly developed hematopoietic system is of recipient or donor origin. This study aimed to evaluate the donor chimerism status using polymerase chain reaction (PCR) of short tandem repeat (STR) in pediatric patients with different malignant and nonmalignant diseases. rnOur study includes 96 children with malignant and nonmalignant disorders. Twenty-six were malignant (ALL, AML, KML) and 70 were nonmalignant (thalassemia, sickle cell disease, immunodeficiency diseases, osteopetrosis, severe aplastic anemia, etc.) Consent form was taken from the patients. The patients underwent transplantation at Balcalı Hospital Bone Marrow Transplant Clinic. Sixteen short tandem repeat alleles of donor and recipients analyzed. STR-based analyses were used before HSCT to determine the informative alelles and after for monitoring post-transplant chimerism.rnThe patients with malignant disorders (26), who underwent HSCT, post-transplant (30th day and 60th day period) monitoring results were 46% complete donor chimerism, 19% mix chimerism and 15% graft rejection or nonengraftment. The patients with nonmalignant disorders (70) chimeric status were 59% complete donor chimerism, 19% mix chimerism and 14% graft rejection or nonengraftment. rnQuantitative monitoring of recipient and donor-derived cells by molecular methods has become an indispensable diagnostic tool in the surveillance of patients undergoing allogeneic HSCT. Our analysis of patient/donor cell chimerism during the post-transplant period reveals donor and recipient information for preemptive therapeutic interventions for clinicians. Using STR–PCR-based serial analysis of microsatellite regions in short time intervals, it could be shown that patients with rapidly increasing mixed chimerism have the highest risk of relapse.rn