Histone acetyltransferases (HATs) and histone deacetylases (HDACs) counteract with each other to regulate gene expression by altering chromatin structure. Aberrant HDAC activity was reported in many human diseases including wide range of cancers, viral infections, cardiovascular complications, auto-immune diseases and kidney diseases. HDAC inhibitors are small molecules designed to block the malignant activity of HDACs. Chemokines and cytokines control inflammation, immunological and other key biological processes and are shown to be involved in various malignancies. Various HDACs and HDAC inhibitors were reported to regulate chemokines and cytokines. Even though HDAC inhibitors have remarkable anti-tumor activity in hematological cancers, they are not effective in treating many diseases and many patients relapse after treatment. However, the role of HDACs and cytokines in regulating these diseases still remain unclear. Therefore, understanding exact mechanisms and effector functions of HDACs are urgently needed to selectively inhibit them and to establish better a platform to combat various malignancies. In this review, we address regulation of chemokines and cytokines by HDACs and HDAC inhibitors and update on HDAC inhibitors in human diseases.

Introduction: Survivors of childhood cancer have an increased risk of developing a subsequent secondary malignant neoplasm (SMN). Among five-year survivors of primary cancer, SMNs account for nearly half of non-relapse deaths, which make them the most frequent cause of non-relapse mortality. Leukemia is the most common childhood cancer and the five-year survival rate of leukemia has drastically improved over the past two decades. Therefore, the chances of developing SMNs are higher in pediatric (0–19 years) leukemia survivors. Methods: The US based Surveillance, Epidemiology, and End Results (SEER-18) database (1973–2014) was probed for SMNs in the pediatric population (age ≤ 19). Variables Sequence-number central, primary site and ICCC3WHO were used to identify the first and second cancers among patients who developed SMN. Results: Our SEER database analysis found 99,380 cases of pediatric primary malignancies (0–19 years), of which 1803 (1.81%) patients developed SMN. The breakdown of SMNs in pediatric leukemia survivors (n = 251) showed thyroid carcinoma (18.33% of cases) as the most common second cancer, followed by sarcoma (15.14%), astrocytoma (10.36%), lymphoma (9.56%), salivary gland carcinoma (7.17%), melanoma (4.38%), and breast cancer (3.98%). Interestingly, we found that over 76% of SMNs that were developed by leukemia patients occurred within 20 years after initial leukemia diagnosis. However, some SMNs occur during later age, for example, the mean age for breast cancer occurrence in leukemia survivors is 26.20 ± 8.53 years after initial leukemia diagnosis. Conclusions: Our study presented comprehensive rates of SMNs among pediatric cancers survivors, and the potential SMNs for pediatric leukemia survivors. This information could we used by oncologists, patients, patient families, and cancer researchers to understand the long-term risks that are associated with the development of SMNs in pediatric leukemia survivors.

The majority of pediatric patients are cured of their primary cancer with current advanced developments in pediatric cancer therapy. However, survivors often experience long-term complications from therapies for primary cancer. The delayed mortality rate has been decreasing with the effort to reduce the therapeutic exposure of patients with pediatric cancers. Our study investigates the incidence of sarcoma as second cancer in pediatric cancer survivors. We present a 9-year-old male who survived embryonal hepatoblastoma diagnosed at 22 months of age. At 4.5 years of age, he presented with a non-metastatic primitive neuroectodermal tumor (PNET) of the left submandibular area. He has no evidence of recurrence of either cancer for 51 months after finishing all chemotherapy and radiotherapy. We used the Surveillance, Epidemiology, and End Results (SEER) database to identify the current rate of second sarcomas in pediatric cancer survivors. Our literature review and large population analysis emphasize the impact of sarcoma as a second malignancy and provide help to physicians caring for pediatric cancer survivors.