Chemotherapy Induced Cardiomyopathy: Pathogenesis, Monitoring and Management

The survival rate of cancer patients has greatly increased over the last 20 years. However, to achieve this result, a considerable price has been paid in terms of the side effects associated with the intensive anticancer treatment. The most common adverse effect is cardiotoxicity which may compromise the clinical effectiveness of chemotherapy, affecting the patient's survival and quality of life independently of the oncological prognosis. There are 2 types of cardiac toxicities, type I which is more serious and result in permanent damage to the myocardium and type II which is usually reversible. Chemotherapies varies in their incidence of inducing cardiomyopathy, and the onset which may occur acutely (during or shortly after treatment), sub-acutely (within days or weeks after completion of chemotherapy) or chronically (weeks to months after drug administration). Cardiac events associated with chemotherapy may consist of mild blood pressure changes, thrombosis, Electrocardiographic (ECG) changes, arrhythmias, myocarditis, pericarditis, myocardial infarction, cardiomyopathy, cardiac failure (left ventricular failure), and congestive heart failure (CHF). The risk for such effects depends upon: cumulative dose, rate of drug administration, mediastinal radiation, advanced age, younger age, female gender, pre-existing heart disease and hypertension. Serial measurements of LVEF and fractional shortening are the most common indices monitored to assess left ventricular systolic function and cardiotoxicity. This can be achieved by 2-dimensional, M-mode and color Doppler echocardiographic examination; also Cardiac troponins as a biological marker for myocardial damage can be used for monitoring in patients received anthracyclines. Angiotensin-converting enzyme (ACE) inhibitors (ACEIs) have been shown to slow the progression of left ventricular dysfunction in several different clinical settings, including anthracycline-induced cardiomyopathy. Carvedilol and probably with anti-oxidants like Probucol and vitamin E benefits also

Characterization of regulatory sequences in alternative promoters of hypermethylated genes associated with tumor resistance to cisplatin

The development of cisplatin resistance in human cancers is controlled by multiple genes and leads to therapeutic failure. Hypermethylation of specific gene promoters is a key event in clinical resistance to cisplatin. Although the usage of multiple promoters is frequent in the transcription of human genes, the role of alternative promoters and their regulatory sequences have not yet been investigated in cisplatin resistance genes. In a new approach, we hypothesized that human cancers exploit the specific transcription factor-binding sites (TFBS) and CpG islands (CGIs) located in the alternative promoters of certain genes to acquire platinum drug resistance. To provide a useful resource of regulatory elements associated with cisplatin resistance, we investigated the TFBS and CGIs in 48 alternative promoters of 14 hypermethylated cisplatin resistance genes previously reported. CGIs prone to methylation were identified in 28 alternative promoters of 11 hypermethylated genes. The majority of alternative promoters harboring CGIs (93%) were clustered in one phylogenetic subclass, whereas the ones lacking CGIs were distributed in two unrelated subclasses. Regulatory sequences, initiator and TATA-532 prevailed over TATA-8 and were found in all the promoters. B recognition element (BRE) sequences were present only in alternative promoters harboring CGIs, but CCAAT and TAACC were found in both types of alternative promoters, whereas downstream promoter element sequences were significantly less frequent. Therefore, it was hypothesized that BRE and CGI sequences co-localized in alternative promoters of cisplatin resistance genes may be used to design molecular markers for drug resistance. A more extensive knowledge of alternative promoters and their regulatory elements in clinical resistance to cisplatin is likely to usher novel avenues for sensitizing human cancers to treatment.Cancer Prevention and Research Institute of Texas (CPRIT; no. RP130266

The Role of Extracellular Vesicles as Modulators of the Tumor Microenvironment, Metastasis and Drug Resistance in Colorectal Cancer.

Colorectal cancer (CRC) is one of the most common cancers worldwide, with high morbidity and mortality rates. A number of factors including modulation of the tumor microenvironment, high metastatic capability, and resistance to treatment have been associated with CRC disease progression. Recent studies have documented that tumor-derived extracellular vesicles (EVs) play a significant role in intercellular communication in CRC via transfer of cargo lipids, proteins, DNA and RNAs to the recipient tumor cells. This transfer influences a number of immune-related pathways leading to activation/differentiation/expression of immune cells and modulation of the tumor microenvironment that plays a significant role in CRC progression, metastasis, and drug resistance. Furthermore, tumor-derived EVs are secreted in large amounts in biological fluids of CRC patients and as such the expression analysis of EV cargoes have been associated with prognosis or response to therapy and may be a source of therapeutic targets. This review aims to provide a comprehensive insight into the role of EVs in the modulation of the tumor microenvironment and its effects on CRC progression, metastasis, and drug resistance. On the other hand, the potential role of CRC derived EVs as a source of biomarkers of response and therapeutic targets will be discussed in detail to understand the dynamic role of EVs in CRC diagnosis, treatment, and management

Patterns of Cancer Incidence Among the Population of Qatar: A Worldwide Comparative Study

Background: Cancer is a major public health problem all over the world. Monitoring the evolution of the cancer burden in the State of Qatar is of great value but has never been explored in depth. Aims: The aim of the study was to determine the incidence patterns of cancer cases, assess trends during the period 1991-2006 and make comparisons with other countries. Methods: This was a retrospective cohort study based on the Cancer disease registry of Al Amal Cancer hospital, State of Qatar, from 1991-2006. All Qataris and non-Qataris, males and females, who were diagnosed with any type of cancer were included in this study. The diagnostic classification of definite cancer cases was made according to the International Classification of Disease 10th revision (ICD-10). Results: A total of 5,825 cancer cases were registered in Qatar during the period 1991-2006 with 56.7% in males and 43.3% in females, 35.6% in Qataris and 64.4% in non-Qataris. Incidence rates per 100,000 population showed that lung (5.9), lymph node (5.9), bone marrow (4.1) and connective tissue (3.9) were the top major cancers in men. In women, breast (30.1), genital organs (9), lymph node (6.8), rectum (6.1) and thyroid (5.7) cancers were the leading cancers. There was a sharp rise in the total number of cancer cases during the period 2002-2006 of 57.1% compared to the period 1991-1996. The incidence rate of cancer cases increased with increasing age in all cancer types except for breast cancer in women above 65 years old. During the study period, the five most common cancers among women were different from those in men. The incidence rate per 100,000 population of all cancer types in Qatar (63.1) was remarkably lower than the other Middle East countries and the UK. Conclusions: Cancer is an important public health problem in Qatar, with increase in incidence with age. Incidence rates of all cancers were higher across all age groups of women compared to men. Lung cancer was the most frequent cancer diagnosed in men and breast cancer in women. More epidemiological studies are now required to elucidate the patterns of cancer and related risk factors

Inducing Angiogenesis, a Key Step in Cancer Vascularization, and Treatment Approaches

Angiogenesis is a term that describes the formation of new blood and lymphatic vessels from a pre-existing vasculature. This allows tumour cells to acquire sustenance in the form of nutrients and oxygen and the ability to evacuate metabolic waste. As one of the hallmarks of cancer, angiogenesis has been studied extensively in animal and human models to enable better understanding of cancer biology and the development of new anti-cancer treatments. Angiogenesis plays a crucial role in the process of tumour genesis, because solid tumour need a blood supply if they are to grow beyond a few millimeters in size. On the other hand, there is growing evidence that some solid tumour exploit existing normal blood supply and do not require a new vessel formation to grow and to undergo metastasis. This review of the literature will present the current understanding of this intricate process and the latest advances in the use of angiogenesis-targeting therapies in the fight against cancer

The first Middle East and North Africa expert consensus recommendations for management of advanced gastric cancer

Gastric cancer (GC) ranks as the fifth most prevalent cancer and the fourth deadliest cancer worldwide. In the Middle East and North Africa (MENA) region, GC represents about 4.8% of cancer cases with more than 35,000 new cases in 2020. To strengthen and improve the management of this cancer in the region, a group of MENA experts in the field of GC developed the first MENA consensus recommendations for the management of advanced GC. A total of 28 statements were drafted, discussed and voted on, using a modified Delphi process, during a virtual consensus meeting. The statements addressed the areas of epidemiology, biomarkers and treatment