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Abstract Acute myeloid leukemia (AML) is a serious, life-threatening, and hardly curable hematological malignancy that affects the myeloid cell progenies and challenges patients of all ages but mostly occurs in adults. Although several therapies are available including chemotherapy, allogeneic hematopoietic stem cell transplantation (alloHSCT), and receptor-antagonist drugs, the 5-year survival of patients is quietly disappointing, less than 30%. alloHSCT is the major curative approach for AML with promising results but the treatment has severe adverse effects such as graft-versus-host disease (GVHD). Therefore, as an alternative, more efficient and less harmful immunotherapy-based approaches such as the adoptive transferring T cell therapy are in development for the treatment of AML. As such, chimeric antigen receptor (CAR) T cells are engineered T cells which have been developed in recent years as a breakthrough in cancer therapy. Interestingly, CAR T cells are effective against both solid tumors and hematological cancers such as AML. Gradually, CAR T cell therapy found its way into cancer therapy and was widely used for the treatment of hematologic malignancies with successful results particularly with somewhat better results in hematological cancer in comparison to solid tumors. The AML is generally fatal, therapy-resistant, and sometimes refractory disease with a disappointing low survival rate and weak prognosis. The 5-year survival rate for AML is only about 30%. However, the survival rate seems to be age-dependent. Novel CAR T cell therapy is a light at the end of the tunnel. The CD19 is an important target antigen in AML and lymphoma and the CAR T cells are engineered to target the CD19. In addition, a lot of research goes on the discovery of novel target antigens with therapeutic efficacy and utilizable for generating CAR T cells against various types of cancers. In recent years, many pieces of research on screening and identification of novel AML antigen targets with the goal of generation of effective anti-cancer CAR T cells have led to new therapies with strong cytotoxicity against cancerous cells and impressive clinical outcomes. Also, more recently, an improved version of CAR T cells which were called modified or smartly reprogrammed CAR T cells has been designed with less unwelcome effects, less toxicity against normal cells, more safety, more specificity, longer persistence, and proliferation capability. The purpose of this review is to discuss and explain the most recent advances in CAR T cell-based therapies targeting AML antigens and review the results of preclinical and clinical trials. Moreover, we will criticize the clinical challenges, side effects, and the different strategies for CAR T cell therapy.

Abstract Objectives Metastases are common in non-cirrhotic livers but are considered unlikely in the setting of cirrhosis. However, the degree of fibrosis in cirrhosis may vary; thus metastases may still access the liver vasculature and present as a mass in cirrhotic livers. This possibility may affect pathologists’ diagnostic algorithms when faced with a liver mass biopsy. Methods We hypothesized that metastases can occur in cirrhotic livers if fibrous remodeling is not severe or abnormal veno-arterial shunting exists to override an obstructed portal system. We searched departmental archives for cirrhotic livers with masses, categorizing fibrosis by Laennec staging: 4A = mild cirrhosis, 4B = moderate, 4 C = severe. Results Of 1453 cirrhotic livers with masses, 1429 were primary tumors and 24 were metastases (1.7 %). Of livers with metastases, most had 4A or 4B cirrhosis by Laennec staging (n = 17; 71 %). Eleven patients were evaluated by ultrasound Doppler; 2 of 5 with Laennec 4 C had reversal of portal vein flow, but all 4A & 4B patients had patent portal veins without reversed flow. Echocardiograms (13 patients) showed no ventricular or atrial septal defects or arteriovenous shunts. Conclusions Metastases are uncommon in cirrhotic livers, accounting for 1.7 % of masses. Most involved livers had mild or moderate cirrhosis (Laennec 4A/4B) and patent portal veins; however, as some Laennec 4 C cases also contained metastases, obstructed portal access may not be enough to deter metastatic access.

AimBarrett's esophagus (BE) is a predisposing factor of esophageal adenocarcinoma/gastroesophageal junction adenocarcinoma (ECA/GEJ Aca). BE patients are stratified and subsequently monitored according to the risk of malignant progression by the combination of endoscopy and biopsy. This study is to evaluate the maspin expression patterns as early diagnostic markers of malignancy in BE patients.Materials and methodsImmunohistochemistry (IHC) staining was performed on 62 archival core biopsies from 35 patients, including BE without dysplasia (intestinal metaplasia, IM), BE with low grade dysplasia, BE with high grade dysplasia, carcinoma in situ, and well to poorly differentiated ECA/GEJ Aca (PD-ECA/GEJ Aca). The intensity and the subcellular distribution of immunoreactivity were evaluated microscopically. Statistical analysis was performed using the χ2 and Fisher exact tests.ResultsThe level of epithelial-specific tumor suppressor maspin protein inversely correlated with the progression from IM to PD-ECA/GEJ Aca. Lesions of each pathological grade could be divided into subtypes that exhibited distinct maspin subcellular distribution patterns, including nuclear only (Nuc), combined nuclear and cytoplasmic (Nuc+Cyt), cytoplasmic only (Cyt) and overall negligible (Neg). The Cyt subtype, which was minor in both IM and dysplasia (approximately 10%), was predominant in ECA/GEJ Aca as early as well-differentiated lesions (more than 50%: p = 0.0092). In comparison, nuclear staining of the tumor suppressor TP53 was heterogeneous in dysplasia, and did not correlate with the differentiation grades of ECA/GEJ Aca.ConclusionThe Cyt subtype of maspin expression pattern in core biopsies of BE patients may serve as a molecular marker for early diagnosis of ECA/GEJ Aca.

Burkholderia pseudomallei is a Gram-negative, facultative intracellular bacillus and the etiologic agent of melioidosis, a severe disease in Southeast Asia and Northern Australia. Like other multidrug-resistant pathogens, the inherent antibiotic resistance of B. pseudomallei impedes treatment and highlights the need for alternative therapeutic strategies that can circumvent antimicrobial resistance mechanisms. In this work, we demonstrate that host prostaglandin E2 (PGE2) production plays a regulatory role in the pathogenesis of B. pseudomallei. PGE2 promotes B. pseudomallei intracellular survival within macrophages and bacterial virulence in a mouse model of pneumonic melioidosis. PGE2-mediated immunosuppression of macrophage bactericidal effector functions is associated with increased arginase 2 (Arg2) expression and decreased nitric oxide (NO) production. Treatment with a commercially-available COX-2 inhibitor suppresses the growth of B. pseudomallei in macrophages and affords significant protection against rapidly lethal pneumonic melioidosis when administered post-exposure to B. pseudomallei-infected mice. COX-2 inhibition may represent a novel immunotherapeutic strategy to control infection with B. pseudomallei and other intracellular pathogens.

A comprehensive review was performed for the identification of female-specific cancer from 1st January 1980 up to 31st May 2016. Overall, the risk of breast cancer was noticed to be the highest among Chinese women (RD 0.42, CI 0.41 - 0.43). Malay women were noticed to have a 22.0% higher likelihood of breast cancer than Indian women (RD 0.22, CI 0.21 - 0.22), but 20% lower than Chinese women (RD -0.20, CI -0.21 -0.19). Cervical cancer was ranked second in Malaysia, with an average ASR of 17.3. Indians had the lowest risk of developing cervical cancer as compared to Malays (RD 0.22, CI 0.18 - 0.26) and Chinese (RD 0.46, CI 0.41 - 0.51). Ovarian cancer was ranked fourth among Malaysians with an average ASR of 7.3 over the seven-year cancer registry. Indians had a lower ovarian cancer risk than Chinese (RD 0.29, CI 0.27 - 0.31) and Malays (RD 0.36, CI 0.34 - 0.38). In 2008, endometrial cancer was ranked sixth in the most-occurring cancers among Malaysian females (average ASR 6.5). Malay females were noticed to have a slightly lower risk of corpus uteri carcinoma than Chinese women (RD -0.06, CI -0.09 -0.03), but are at a higher risk than Indian women (RD 0.25, CI 0.23, - 0.28). The age group of 50-59 has the peak incidence for breast cancer and cervical cancer. Endometrial cancer incidence peaked in the age group of 60-69 years while ovarian cancer incidence rose sharply after the age of 40 years. [ABSTRACT FROM AUTHOR]

Cancer is considered a life-threatening disease, and several factors are involved in its development. Chemokines are small proteins that physiologically exert pivotal roles in lymphoid and non-lymphoid tissues. The imbalance or dysregulation of chemokines has contributed to the development of several diseases, especially cancer. CCL19 is one of the homeostatic chemokines that is abundantly expressed in the thymus and lymph nodes. This chemokine, which primarily regulates immune cell trafficking, is involved in cancer development. Through the induction of anti-tumor immune responses and inhibition of angiogenesis, CCL19 exerts tumor-suppressive functions. In contrast, CCL19 also acts as a tumor-supportive factor by inducing inflammation, cell growth, and metastasis. Moreover, CCL19 dysregulation in several cancers, including colorectal, breast, pancreatic, and lung cancers, has been considered a tumor biomarker for diagnosis and prognosis. Using CCL19-based therapeutic approaches has also been proposed to overcome cancer development. This review will shed more light on the multifarious function of CCL19 in cancer and elucidate its application in diagnosis, prognosis, and even therapy. It is expected that the study of CCL19 in cancer might be promising to broaden our knowledge of cancer development and might introduce novel approaches in cancer management. This study is focused on the role of CCL19 in cancer development. It has been shown that CCL19 exerts conflicting functions in the tumor microenvironment. Using CCL19-based therapies might introduce novel approaches in cancer treatment. [ABSTRACT FROM AUTHOR]

Acute myeloid leukemia (AML) is a serious, life-threatening, and hardly curable hematological malignancy that affects the myeloid cell progenies and challenges patients of all ages but mostly occurs in adults. Although several therapies are available including chemotherapy, allogeneic hematopoietic stem cell transplantation (alloHSCT), and receptor-antagonist drugs, the 5-year survival of patients is quietly disappointing, less than 30%. alloHSCT is the major curative approach for AML with promising results but the treatment has severe adverse effects such as graft-versus-host disease (GVHD). Therefore, as an alternative, more efficient and less harmful immunotherapy-based approaches such as the adoptive transferring T cell therapy are in development for the treatment of AML. As such, chimeric antigen receptor (CAR) T cells are engineered T cells which have been developed in recent years as a breakthrough in cancer therapy. Interestingly, CAR T cells are effective against both solid tumors and hematological cancers such as AML. Gradually, CAR T cell therapy found its way into cancer therapy and was widely used for the treatment of hematologic malignancies with successful results particularly with somewhat better results in hematological cancer in comparison to solid tumors. The AML is generally fatal, therapy-resistant, and sometimes refractory disease with a disappointing low survival rate and weak prognosis. The 5-year survival rate for AML is only about 30%. However, the survival rate seems to be age-dependent. Novel CAR T cell therapy is a light at the end of the tunnel. The CD19 is an important target antigen in AML and lymphoma and the CAR T cells are engineered to target the CD19. In addition, a lot of research goes on the discovery of novel target antigens with therapeutic efficacy and utilizable for generating CAR T cells against various types of cancers. In recent years, many pieces of research on screening and identification of novel AML antigen targets with the goal of generation of effective anti-cancer CAR T cells have led to new therapies with strong cytotoxicity against cancerous cells and impressive clinical outcomes. Also, more recently, an improved version of CAR T cells which were called modified or smartly reprogrammed CAR T cells has been designed with less unwelcome effects, less toxicity against normal cells, more safety, more specificity, longer persistence, and proliferation capability. The purpose of this review is to discuss and explain the most recent advances in CAR T cell-based therapies targeting AML antigens and review the results of preclinical and clinical trials. Moreover, we will criticize the clinical challenges, side effects, and the different strategies for CAR T cell therapy. [ABSTRACT FROM AUTHOR]

Introduction: Coronavirus disease 2019 (COVID-19) is declared as pandemic by the World Health Orgnazation (WHO) on March 2020. One of the heavily utilized measures during this pandemic is vitamin C (aka ascorbic acid). Unfortunately, vitamin C has been associated with glucose measurement interference and thus this study highlights the elevated levels of blood glucose correlated with the presence of vitamin C interference. Methodology: Thirty samples were selected randomly and the blood glucose were measured prior and post the addition of spiked standard concentrations of vitamin C. The interference of vitamin C with glucose readings in COVID-19 pandemic were evaluated and observed employing the Auto Chemistry Analyzer machine. Results: The addition of ascorbic acid (vitamin C) standards (spikes) into the isolated samples shows a correlated increment in the reading measures. Thereafter, the increments of Random Blood Sugar (RBS) readings after being spiked with the vitamin C standards shows a logarithmic correlation with good interesting R-squared (R² = 0.9921). Conclusions: The authors find that the presence of vitamin C in blood actively and significantly alters the glucose level readings especially with the highly consumption of vitamin C during the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Background: Tranexamic acid is used to treat or prevent excessive blood loss. Moreover, tranexamic acid is reported to treat the UV lightinduced hyperpigmentation. Several tranexamic acid esters were approved to have topical skincare, however, tranexamic acid ethyl ester was not. In this work, a vehicle-controlled, double-blinded, and randomized clinical study was conducted for both tranexamic acid and its synthesized ethyl ester. Methods: a well-established protocol was adopted to synthesize ethyl-4-(Aminomethyl)Cyclohexanecarboxylate from tranexamic acid and ethanol. Three gel preparations were applied. These contained tranexamic acid, tranexamic acid ethyl ester, and vehicle (gel base). These three prepared gels were applied to thirty-six subjects of three equally-divided groups for thirty days' period. Results: The synthesis shows 90% yield with purity > 99.7%. While the clinical findings were significant for both tranexamic acid (P = .01) and tranexamic acid ethyl ester (P < .001) whereas it was insignificant for the gel vehicle (P = .176). Conclusion: The authors concluded that both tranexamic acid and tranexamic acid ethyl ester topical gels are considered favourable choices to counteract facial hyperpigmentation. [ABSTRACT FROM AUTHOR]