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Journal of Clinical Haematology
ISSN: 2766-4686
Volume 1, Issue 4, p107-143
Articles published in this issue are Open Access and licensed under Creative Commons Attribution License (CC BY NC) where the readers can reuse, download, distribute the article in whole or part by mentioning proper credits to the authors.
Gemcitabine in the Era of Cancer Immunotherapy
Gemcitabine is a synthetic pyrimidine nucleoside analogue which is administered intravenously as a chemotherapeutic to treat numerous cancers. Gemcitabine requires transport into cells and activation by phosphorylation, the resulting gemcitabine triphosphate is incorporated into newly synthesized DNA during cell division, inhibiting further DNA synthesis and causing cell death. Gemcitabine is used to treat cancers including those of the pancreas, lung, breast, colon, and ovary either as first or second line treatments as a single agent or in combination.
J Clin Haematol, 2020, Volume 1, Issue 4, p107-120 | DOI: 10.33696/haematology.1.016Targeted Immune Therapy as Example of Paul Ehrlich’s “Magic Bullets” Developed More than 100 Years Ago
In the article by Gerhard Zugmaier, Antibodies in hematology by the example of acute lymphoblastic leukemia, Der Internist 10 (2019) 1032–1035, the application of antibodies in hematology was described by using the example of acute lymphoblastic leukemia. Antibodies have become an essential element of treatment for patients with hematological tumors. This concept was developed more than 100 years ago in a different context. The German physician Paul Ehrlich (1854-1915) said, that for the defense against bacteria “antibodies” were be responsible. In the antibodies Ehrlich saw therapeutic compounds, that like “magic bullets” would find their target and only destroy this target without affecting the organism. Paul Ehrlich became inspired by a scene in the German opera “Der Freischütz” (“The marksman”) by the composer Carl Maria von Weber.
J Clin Haematol, 2020, Volume 1, Issue 4, p121-122 | DOI: 10.33696/haematology.1.017CART Cells: A New Dawn in Cancer Immunotherapy
Over the last 10 to 15 years the treatment of patients with hematologic malignancies has seen the blossom of a large number of new agents and even new treatment strategies. Monoclonal antibodies (MoAb), TKI inhibitors, checkpoint inhibitors have been introduced in the daily clinical practice and contributed significantly to the improvement of the outcome of hematologic patients. Along with the development of these new drugs, cellular therapies, namely chimeric antigen receptor-engineered T (CART) cells, have revolutionized the therapeutic paradigm of patients with B-cell lymphoid malignancies and acute lymphoblastic leukemia (ALL).
J Clin Haematol, 2020, Volume 1, Issue 4, p123-124 | DOI: 10.33696/haematology.1.018Unmasking the Master of Disguise: Defining Advancements in Diagnosis of Intravascular Large B-cell Lymphoma
Intravascular B cell lymphoma (IVBCL) is notoriously difficult to diagnose as the clinical manifestations are protean, and the patterns seen with routine labs and imaging are non-specific. Furthermore, the disease follows an aggressive course and is often fatal within a matter of weeks to months from symptom onset, unless recognized and treated appropriately. This has historically meant that diagnosis was made at autopsy for many patients. Over the past few decades, however, scientific and clinical literature have slowly accumulated to better characterize and raise clinical awareness of this disease. In this paper, we will review the characteristics that make this diagnosis challenging, and then discuss new and emerging diagnostic avenues.
J Clin Haematol, 2020, Volume 1, Issue 4, p125-131 | DOI: 10.33696/haematology.1.019Anticancer and Antiviral Activity of the Pyridine-Biphenyl Glycoside System
According to the report published recently by the World Health Organization, the number of cancer cases in the world will increase to 22 million by 2030. So, the anticancer drug research and development is taking place in the direction where the new entities are developed which are low in toxicity and are with improved activity. Pyridine and their pyridine-biphenyl system derivatives represent a very important class of heterocyclic compounds, which have a diverse therapeutic area. Recently, many active compounds synthesized are very effective; natural products isolated with pyridine moiety have also shown to be potent towards cancer.
J Clin Haematol, 2020, Volume 1, Issue 4, p132-143 | DOI: 10.33696/haematology.1.020Karyotypic Profile of Chronic Myeloid Leukemia in Patients Diagnosed at Tertiary Level in Afghanistan
Balanced translocation resulting in fusion of the Abelson gene (ABL1) from chromosome 9q34 with the breakpoint cluster region (BCR) gene on chromosome 22q11.2 is the pathognomonic molecular driver of CML. The resulting BCRABL 1 fusion gene is both the diagnostic as well as therapeutic target of CML. The first agent with tyrosine kinase inhibitor activity that was licenced in 2000 for treatment of CML patients, was Imatinib, gradually followed by multiple agents with higher efficacy.
Chimeric Antigen Receptor CAR NK Cells Emerging Immunotherapy for the Treatment of Cancer
Although NK cells are recognized as effector lymphocytes of the innate immune system, they also regulate the adaptive immune response by releasing inflammatory cytokines and developing immunological memory. Unlike other lymphocytes such as T or B cells, NK cells do not express rearrangeable, antigen-specific receptors.
Angioimmunoblastic T cell Lymphoma Microenvironment
Angioimmunoblastic T cell lymphoma (AITL) is one of the most common T-cell lymphomas, second only to peripheral T-cell lymphoma not otherwise specified (PTCL-NOS). Initially AITL was considered a non-malignant lymphadenopathy with immune hyperactivation, nowadays being classified as a PTCL.
Safety of Using Rituximab Therapy During COVID-19 Pandemic
Our modern world is facing extraordinary circumstances while passing through a serious pandemic caused by the novel coronavirus (COVID-19) which may lead to multi-organ system failure & death. Bcell depletion could compromise antiviral immunity, which makes the safety of rituximab use in the COVID19 era unclear.
Deubiquitinase as Potential Targets for Cancer Immunotherapy
During the last few decades, immunotherapy is considered to be an important approach to help our immune system to fight various kinds of diseases, such as tumor. Sometimes, it works very well for some types of cancers, for example: bladder cancer, colorectal cancer, breast cancer and lymphoma.
Reduced BCR Signaling and a Metabolic Shift Accompanies Malignant Progression of Follicular Lymphoma: A Lesson from Transcriptomics
In the manuscript entitled “The ion channels and transporters gene expression profile indicates a shift in excitability and metabolisms during malignant progression of Follicular Lymphoma”, we reported recent advances in our understanding of how the gene expression profile of ion channels and transporters (ICT-GEP) contributes to identify specific signatures associated with Follicular Lymphoma (FL), with those FL that acquire chemoresistance after a relapsing-remitting course, and with the more aggressive Diffuse Large Cell Lymphoma (DLBCL), which in some cases represent the evolution of FLs.
Role of the Gut Microbiome in the Modulation of Cancer Immunotherapy Response
The gut microbiome or gut flora is a vast community of microorganisms such as bacteria, viruses, protozoa, and fungi that inhabit the digestive tract of the human and other animals. In the human body, bacterial species colonize into the oral cavity, skin, vagina, and placenta, however, the largest population of microorganisms resides in the intestine. The majority of gut microbiota belong to the phyla Firmicutes, Bacteroidetes, Proteobacteria and Actinobacteria.
Sentinel Lymph Node Biopsy after Neoadjuvant Chemotherapy for Breast Cancer
Breast cancer is the second most common cancer worldwide, affecting nearly one in eight women. Accurate cancer staging is essential for determining the patient’s prognosis and for choosing the appropriate treatment. The staging system most often used is the American Joint Committee on Cancer (AJCC) TNM system, where T refers to the size of the tumor, N refers to spread of the primary cancer to nearby lymph nodes, and M refers to the spread of metastasis to distant sites in the body.
Botulinum Toxin: The Promising Future of Prostate Cancer Treatment
Peripheral nerves have been shown to modulate the growth and spread of tumours in the prostate, feeding both cancer cells and the stroma in the tumour environment. Several in vitro and in vivo studies have reported the effect of botulinum toxin (BT) on tumour tissue in the prostate. BT in humans has been observed to cause increased apoptosis of cancer cells, with morphological changes characterized by extensive degenerative and atrophic areas of cancer, reduced cytoplasm, and pyknotic nuclei, compared to the characteristics of cancer tissues injected with saline solution.
Molecular Biology for BCR-ABL1 Quantification for Chronic Myeloid Leukemia Monitorization and Evaluation
Chronic Myeloid Leukemia (CML) is a clonal disorder originated by a pluripotent hematopoietic stem cell, which presents the translocation t(9;22) (q34;q11) in 90% of the cases. This genetic abnormality is a balanced translocation between Abelson Murine Leukemia (ABL) located in chromosome 9 with the Breakpoint Cluster Region (BCR) gene at chromosome 22, generating Philadelphia chromosome (Ph) or BCR-ABL1, which codes an oncoprotein of 210 kDa. This alteration represents a hallmark in oncology and for CML research, diagnosis, and prognosis.
NOXA the BCL-2 Family Member behind the Scenes in Cancer Treatment
NOXA is a critical mediator of stress responses to anticancer drugs. This BH3-only protein sets the apoptotic threshold in cancer cells in response to chemotherapies by counteracting the prosurvival BCL-2 family protein MCL-1. A complex and dynamic network relying on both highly controlled gene transcription activity and protein degradation by proteasome, regulates cellular NOXA levels from low in steady state to rapidly enhanced upon stressful condition.
Neoadjuvant Chemotherapy Followed by Fertility Sparing Surgery in Stage 1B2 Cervical Cancer
In 2020 we published a series of 18 patients who underwent neoadjuvant chemotherapy (NACT) and vaginal radical trachelectomy (VRT) as a fertility sparing alternative in stage 1B2 cervical cancer.
CTLA-4 and PD-L1 or PD-1 Pathways: Immune Checkpoint Inhibitors and Cancer Immunotherapy
The immune system developed certain checks and balance to control or inhibit the reactivity against normal cells of the body. Uncontrolled immune responses to the non-self entities such as bacteria, viruses, parasites, or mutated self-antigens can cause an inflammatory reaction and autoimmune diseases.
Cancer Nanomedicine: Strategies to Enhance Tumor Delivery and Immunotherapy
Cancer nanomedicine was originally developed for more efficient delivery of chemotherapeutic agents into tumor, and has been extensively employed as a therapeutic for cancer treatment owing to its unique features in drug delivery, diagnosis and imaging, as well as the therapeutic nature of some nanomaterials themselves.
Targeting "Do Not Eat Me" Signal CD47 in Cancer Immunotherapy
Cells of the innate and adaptive arm of the immune system including macrophages, natural killer (NK) cells, neutrophils, T cells, and B cells, etc. are crucial for the maintenance of the body’s homeostatic balance and prevention of multiple diseases including cancer.
Late ECG Changes after Cisplatin-Based Chemotherapy in Testicular Cancer Survivors
Introducing cisplatin-based therapy into testicular cancer treatment represents a substantial progress in therapy leading to a longer survival of patients and less adverse effects; currently it represents the standard therapy.
Immunotherapy in Pediatric Acute Lymphoblastic Leukemia
Leukemia is the most common childhood malignancy and cause of pediatric cancer death. Significant advances in the cure rates of B-cell acute lymphoblastic leukemia (B-ALL) and T-cell acute lymphoblastic leukemia (T-ALL) have been achieved; however, patients with refractory or relapsed B-ALL or T-ALL continue to have poor outcomes. Immunotherapy is a revolutionary treatment aimed to improve survival and reduce the toxicity of chemotherapy by harnessing the patient’s own immune system to target cancer cells.
Small-molecule Interferon Inducers for Cancer Immunotherapy Targeting Non-T cell-inflamed Tumors
Since the discovery of escaping mechanism of tumor from negative immune regulation, the paradigm of drug discovery for anti-cancer agents has been dramatically shifted to cancer immunotherapy (e.g., dendritic cell therapy, CAR-T cell therapy, or antibody therapy) by stimulating patient’s immune system to treat cancer.
New N-ribosides and N-mannosides of Rhodamine Derivatives for Suppressing Leukemia Cell Line Growth
Leukemia is a tumor of the primary blood-forming cells. leukemia is not only a cancer of the white blood cells but also it originates in other blood cell types. Types of leukemia are categorized based on the rate of growth to acute (fastgrowing) or chronic (slower growing), and whether it arises in myeloid cells or lymphoid cells. Different types of leukemia have a different line of treatment and prognosis.
Lack of Prognostic Significance of Pretreatment Total Metabolic Tumor Volume on Event-free Survival at 24 Months in Diffuse Large B-cell Lymphoma
Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease with variable outcomes. The majority of patients benefit from chemo-immunotherapy; however, 30 to 40% relapse after first-line treatment, and 10% are refractory to first-line treatment. This variability in outcome has led to the identification of prognostic factors to stratify patients based on their risk of relapse. The five-factor international prognostic index (IPI) was formulated for such risk stratification more than 20 years ago, based on clinical information obtained from patients with aggressive lymphomas treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-like chemotherapy. The addition of rituximab to CHOP chemotherapy led to improved outcomes, diminishing the discriminatory capacity of IPI amongst risk groups. Efforts to enhance the prognostic model by adding or defining new factors have only led to minor improvements without the ability to identify patients at risk of an inferior outcome.
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