• Biomolecules & Therapeutics
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• 제32권4호
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• pp.424-431
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• 2024

Among the therapeutic strategies in cancer immunotherapy-such as immune-modulating antibodies, cancer vaccines, or adoptive T cell transfer-T cells have been an attractive target due to their cytotoxicity toward tumor cells and the tumor antigen-specific binding of their receptors. Leveraging the unique properties of T cells, chimeric antigen receptor-T cells and T cell receptor (TCR)-T cells were developed through genetic modification of their receptors, enhancing the specificity and effectiveness of T cell therapy. Adoptive cell transfer of chimeric antigen receptor-T cells has been successful for the treatment of hematological malignancies. To expand T cell therapy to solid tumors, T cells are modified to express defined TCR targeting tumor associated antigen, which is called TCR-T therapy. This review discusses anti-tumor T cell therapies, with a focus on engineered TCR-T cell therapy. We outline the characteristics of TCR-T cell therapy and its clinical application to non-hematological malignancies.

• 임상간호연구
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• 제20권3호
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• pp.384-394
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• 2014

Purpose: To improve professional intensive care by analyzing admission causes, causes of death, disease conditions, and treatment processes in patients with hematological malignancies admitted to intensive care units (ICUs) in South Korea. Methods: This was a retrospective study approved by IRB, and conducted on admission with 559 adults, in the hematology ICU of a hospital located in Seoul. The study was carried out from April 2009 to March 2012. Data were analyzed using SAS. Results: Pneumonia was the most frequent cause of ICU admission and death, followed by sepsis. The condition at discharge was death (53.6%), recovery (39.9%), or hopeless (5.1%). Mortality of patients in states of incomplete remission was higher than that of patients with complete remission and of patients with multiple myeloma, severe aplastic anemia, and lymphoma. Conclusion: Results show that pneumonia and sepsis are the most frequent causes of ICU admission and for the death of patients with hematological malignancies. The most frequent status at discharge of patients with hematological malignancies was death (53.6%), with mortality of patients at Incomplete Remission status, of mechanically ventilated patients, and of patients on continuous renal replacement therapy (CRRT) being higher than others.

• Asian Pacific Journal of Cancer Prevention
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• 제17권4호
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• pp.1847-1850
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• 2016

Background: It is reported that the percentage of smudge cells in the blood smear could be a prognostic indicator in chronic lymphocytic leukemia. However, the clinical significance of smudge cells in other hematological malignancies, solid tumors or non-malignant diseases is less clear. Hence, this study was conducted to survey the clinical significance of smudge cells in hematological cancers and other disorders. Materials and Methods: From January to November, 2015, the clinical data of patients who received blood examination with differential counts for clinical purpose and were found to have smudge cells in the peripheral blood film in Far Eastern Memorial Hospital were selected. The percentage of smudge cells and patient outcomes were evaluated for further univariate and survival analyses. Results: A total of 102 patients with smudge cells in their blood smears were included. Smudge cells were frequently presented in out-of-hospital cardiac arrest (OHCA; n=30), infections (n=23), hematological cancers (n=23) and solid cancers (n=10). There was no relationship between the percentage of smudge cells and the patient mortality in all diseases (OR: 1.08, 95% CI: 0.47-2.48, P=1.000) as well as the OHCA group (OR: 1.91, 95% CI: 0.38-9.60, P=0.694). It was observed that in patients with all cancers with the percentage of smudge cells less than 50% had a lower mortality rate in comparison with those who had the percentage of smudge cells of 50% or more (OR: 22.29, 95% CI: 2.38-208.80, P<0.001). Additionally, it was seemingly that patients with smudge cells of 50% or more had a lower survival rate than those with smudge cells less than 50% in all cancers with follow-up at 2-month intervals, but without statistical significance (P=0.064). Conclusions: Our survey indicated that in all cancers, those who had higher percentage of smudge cells were prone to have poor outcomes when compared with the subjects with lower percentage of smudge cells. This finding was quite different from the results of previous studies in which the race-ethnicity of most study populations was non-Asian; hence, further investigations are required. Besides, there was no apparent association of the percentage of smudge cells with patient outcomes in all diseases, including OHCA.

• Asian Pacific Journal of Cancer Prevention
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• 제13권5호
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• pp.2415-2418
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• 2012

Objective: To investigate the efficacy and safety of voriconazole in treating Chinese patients with hematological malignancies and invasive aspergillosis. Methods: From March 2007 to April 2012, patients with diagnoses confirmed by CT, GM test and/or PCR assays, were recruited into this study. Aspergillosis of all patients were treated with voriconazole 6 mg/kg intravenous infusion (iv) every 12 h for 1 day, followed by 4 mg/kg IV every 12 h for 10-15 days; Then, switch to oral administration that was 200mg every 12h for 4-12 weeks. Efficacy and safety were evaluated according to Practice Guideline of Infectious Diseases Society of America. Results: The overall response rate of 38 patients after voriconazole treatment was 81.6%. The median time to pyretolysis was 4.5 days. Treatment related side effects were mild and found in only 15.8% of cases. No treatment related deaths occurred. Conclusions: Voriconazole can considered to be a safe and effective front-line therapy to treat patients with hematological malignancies and invasive aspergillosis. Alternatively it could be used as a remedial treatment when other antifungal therapies are ineffective.

• Molecules and Cells
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• 제38권6호
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• pp.482-495
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• 2015

Sphingolipids such as ceramide, sphingosine-1-phosphate and sphingomyelin have been emerging as bioactive lipids since ceramide was reported to play a role in human leukemia HL-60 cell differentiation and death. Recently, it is well-known that ceramide acts as an inducer of cell death, that sphingomyelin works as a regulator for microdomain function of the cell membrane, and that sphingosine-1-phosphate plays a role in cell survival/proliferation. The lipids are metabolized by the specific enzymes, and each metabolite could be again returned to the original form by the reverse action of the different enzyme or after a long journey of many metabolizing/synthesizing pathways. In addition, the metabolites may serve as reciprocal biomodulators like the rheostat between ceramide and sphingosine-1-phosphate. Therefore, the change of lipid amount in the cells, the subcellular localization and the downstream signal in a specific subcellular organelle should be clarified to understand the pathobiological significance of sphingolipids when extracellular stimulation induces a diverse of cell functions such as cell death, proliferation and migration. In this review, we focus on how sphingolipids and their metabolizing enzymes cooperatively exert their function in proliferation, migration, autophagy and death of hematopoetic cells, and discuss the way developing a novel therapeutic device through the regulation of sphingolipids for effectively inhibiting cell proliferation and inducing cell death in hematological malignancies such as leukemia, malignant lymphoma and multiple myeloma.

• Asian Pacific Journal of Cancer Prevention
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• 제15권3호
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• pp.1411-1414
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• 2014

Background: Hepatitis B and C are the leading causes of liver diseases worldwide. For hematological and solid malignancy patients undergoing chemotherapy, increases in HBV DNA and HCV RNA levels can be detected which may result in reactivation and hepatitis-related morbidity and mortality. The aim of this study was to determine the seroprevalence of Hbs ag and Anti HCV positivity in patients with solid malignancies undergoing chemotherapy and consequences during follow-up. Materials and Methods: The files of 914 patients with solid malignancies whose hepatitis markers were determined serologically at diagnosis were reviewed retrospectively. All underwent adjuvant/palliative chemotherapy. For the cases with HBV and/or HCV positivity, HBV DNA and HCV RNA levels, liver function tests at diagnosis and during follow-up and the treatment modalities that were chosen were determined. Results: Of 914 cases, Hbs Ag, anti Hbs and anti HCV positivity were detected in 40 (4.4%), 336 (36.8%) and 26 (2.8%) of the cases respectively. All of the Hbs ag positive patients received prophylactic lamuvidine before the start of chemotherapy. In the Hbs ag and anti HCV positive cases, liver failure was not detected during chemotherapy and a delay in chemotherapy courses because of hepatitis was not encountered. Conclusions: Just as with hematological malignancies, screening for HBV and HCV should also be considered for patients with solid tumors undergoing chemotherapy. Prophylactic antiviral therapy for HBV reduces both the reactivation rates and HBV related mortality and morbidity. The clinical impact of HCV infection on patients undergoing chemotherapy is still not well characterized.

• Asian Pacific Journal of Cancer Prevention
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• 제16권18호
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• pp.8525-8531
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• 2016

Background: Cancer has become a major health problem associated with high mortality worldwide, especially in developing countries. The aim of our study was to evaluate the incidence rates of different types of cancer in Sulaymaniyah from January-2006 to January-2014. The data were compared with those reported for other middle east countries. Materials and Methods: This retrospective study depended on data collected from Hiwa hospital cancer registry unit, death records and histopathology reports in all Sulaymaniyah teaching hospitals, using international classification of diseases. Results: A total of 8,031 cases were registered during the eight year period, the annual incidence rate in all age groups rose from 38 to 61.7 cases/100,000 population/year, with averages over 50 in males and 50.7 in females. The male to female ratio in all age groups were 0.98, while in the pediatric age group it was 1.33. The hematological malignancies in all age groups accounted for 20% but in the pediatric group around half of all cancer cases. Pediatric cancers were occluding 7% of total cancers with rates of 10.3 in boys and 8.7 in girls. The commonest malignancies by primary site were leukemia, lymphoma, brain, kidney and bone. In males in all age groups they were lung, leukaemia, lymphoma, colorectal, prostate, bladder, brain, stomach, carcinoma of unknown primary (CUP) and skin, while in females they were breast, leukaemia, lymphoma, colorectal, ovary, lung, brain, CUP, and stomach. Most cancers were increased with increasing age except breast cancer where decrease was noted in older ages. High mortality rates were found with leukemia, lung, lymphoma, colorectal, breast and stomach cancers. Conclusions: We here found an increase in annual cancer incidence rates across the period of study, because of increase of cancer with age and higher rates of hematological malignancies. Our study is valuable for Kurdistan and Iraq because it provides more accurate data about the exact patterns of cancer and mortality in our region.

• Molecules and Cells
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• 제41권8호
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• pp.717-723
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• 2018

Chimeric antigen receptor (CAR) T-cell therapy, an emerging immunotherapy, has demonstrated promising clinical results in hematological malignancies including B-cell malignancies. However, accessibility to this transformative medicine is highly limited due to the complex process of manufacturing, limited options for target antigens, and insufficient anti-tumor responses against solid tumors. Advances in gene-editing technologies, such as the development of Zinc Finger Nucleases (ZFNs), Transcription Activator-Like Effector Nucleases (TALENs), and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR/Cas9), have provided novel engineering strategies to address these limitations. Development of next-generation CAR-T cells using gene-editing technologies would enhance the therapeutic potential of CAR-T cell treatment for both hematologic and solid tumors. Here we summarize the unmet medical needs of current CAR-T cell therapies and gene-editing strategies to resolve these challenges as well as safety concerns of gene-edited CAR-T therapies.

• Nuclear Medicine and Molecular Imaging
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• 제40권2호
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• pp.66-73
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• 2006

Monoclonal antibodies are designed to bind specifically to certain antigen, give therapeutic effect to the target and to be produced in large scale with homogeneity. The monoclonal antibodies conjugated with radionuclide can deliver therapeutic irradiation to the target, and showed successful results in certain malignancies, which is known as radioimmunotherapy. The target-to-background ratio depends on the antigen expression in the target and normal tissues, which is related to the therapeutic efficacy and toxicity in radioimmunotherapy. For the solid tumor beta-ray energy should be high, but lower beta energy is better for the hematological malignancies. I-l31 is widely used in thyroid cancer with low cost and high availability. Labeling monoclonal antibody with I-131 is relatively simple and reproducible. Some preclinical data for the I-131 labeled monoclonal antibodies including acute toxicity and efficacy are available from already published literatures in KIRAMS, physician sponsored clinical trial protocols using Rituximab, KFDA approved anti-CD20 chimeric monoclonal antibody and I-131 were approved by KFDA and currently are ongoing.

• Annals of Clinical Neurophysiology
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• 제25권2호
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• pp.84-92
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• 2023

Background: Clinical spectrum of immunoglobulin M (IgM) monoclonal gammopathy varies from IgM monoclonal gammopathy of unknown significance (IgM-MGUS) to hematological malignancies. We evaluated the clinical features, electrophysiological characteristics, and prognosis of patients with peripheral neuropathy associated with IgM monoclonal gammopathy (PN-IgM MG). Methods: We retrospectively evaluated 25 patients with PN-IgM MG. Peripheral neuropathy was classified as axonal, demyelinating, or undetermined, based on electrophysiological studies. We classified the enrolled patients into the IgM-MGUS and malignancy groups, and compared the clinical and electrophysiological features between the groups. Results: Fifteen patients had IgM-MGUS and 10 had hematologic malignancies (Waldenström's macroglobulinemia: two and B-cell non-Hodgkin's lymphoma: eight). In the electrophysiological evaluation, the nerve conduction study (NCS) criteria for demyelination were met in 86.7% of the IgM-MGUS group and 10.0% of the malignancy group. In particular, the distal latencies of the motor NCS in the IgM-MGUS group were significantly prolonged compared to those in the malignancy group (median, 9.1 ± 5.1 [IgM-MGUS], 4.2 ± 1.3 [malignancy], p = 0.003; ulnar, 5.4 ± 1.9 [IgM-MGUS], 2.9 ± 0.9 [malignancy], p = 0.001; fibular, 9.3 ± 5.1 [IgM-MGUS], 3.8 ± 0.3 [malignancy], p = 0.01; P-posterior tibial, 8.3 ± 5.4 [IgM-MGUS], 4.4 ± 1.0 [malignancy], p = 0.04). Overall treatment responses were significantly worse in the malignancy group than in the IgM-MGUS group (p = 0.004), and the modified Rankin Scale score at the last visit was higher in the malignancy group than in the IgM-MGUS group (2.0 ± 1.1 [IgM-MGUS], 4.2 ± 1.7 [malignancy], p = 0.001), although there was no significant difference at the initial assessment. Conclusions: The risk of hematological malignancy should be carefully assessed in patients with PN-IgM MG without electrophysiological demyelination features.