OBJECTIVETo explore the action mechanism of chlorambucil against mantle cell lymphoma cell line Jeko-1.

METHODSThe effect of chlorambucil on Jeko-1 cell proliferation was measured by MTT method. The effect of chlorambucil on the apoptosis of Jeko-1 cell was detected by Hoechst staining and Annexin V-FITC dual staining. The activation of PI3K/AKT signaling pathway and the expression of BAX, BCL-2, procaspase 3, procaspase 8 and procaspase 9 were detected by Western blot.

RESULTS0, 5, 10, 20 µmol/L chlorambucil could inhibit Jeko-1 cell proliferation at 24, 48, 72 h in a time- and dose-dependent manner. Chlorambucil of 0, 5, 10, 20 µmol/L increased the apoptotic rate of Jeko-1 cells, upregulated the expression of BAX, procaspase 3, procaspase 8, procaspase 9 and PI3K, increased the phosphorylation of AKT and down-regulated the expression of BCL-2.

CONCLUSIONThe chlorambucil can induce the apoptosis of mantle cell lymphoma Jeko-1 cells via blocking PI3K/AKT signaling pathway.

Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Chlorambucil ; Down-Regulation ; Humans ; Lymphoma, Mantle-Cell ; Phosphatidylinositol 3-Kinases ; Phosphorylation ; Signal Transduction

OBJECTIVETo evaluate the efficacy and safety of MAC regimen in the treatment of acute myeloid leukemia(AML) patients older than 55 years.

METHODSA total of 33 relapsed or non-remission AML patients older than 55 years were enrolled in this research. MAC regimen was given as the salvage treatment. Complete remission rate(CR), partial remission rate(PR), overall survival(OS), relapse-free survival(RFS) and adverse effect were analysed.

RESULTSCR rate after the salvage therapy with MAC was 51.1%, partial remission (PR) rate was 6.1%, the overall response rate (ORR) was 57.6%, the median OS was 8 months (1.0-66.0 months), the median relapse-free survival (RFS) was 10.1 months (2.3-40.4 months). Mortality related with salvage treatment in 30 days was 9.1%. Low incidence of severe organ damage were found.

CONCLUSIONMAC can be used as a relative effective and safe regimen for the salvage treatment of the older AML patients.

Antineoplastic Combined Chemotherapy Protocols ; Chlorambucil ; Cytarabine ; Dactinomycin ; Humans ; Leukemia, Myeloid, Acute ; Methotrexate ; Middle Aged ; Recurrence ; Remission Induction ; Salvage Therapy

An Australian cattle dog (case 1: 6-year-old castrated male) and a Shih-Tzu dog (case 2: 8-year-old castrated male) were referred to the Gyeongsang Animal Medical Center due to anorexia and depression. Physical examinations, complete blood counts, serum chemical analysis, radiography, ultrasonography, and bone marrow biopsy were performed. Upon physical examinations of cases 1 and 2, enlargement of superficial lymph nodes was not identified. Hematologic findings in these dogs included leukocytosis with severe lymphocytosis, anemia, and thrombocytopenia. Upon radiography, both dogs showed splenomegaly. Upon examination of a peripheral blood smear in case 1, immature lymphoid cells, featuring decreased nuclear chromatin condensation and nuclear pleomorphism, were present. Biopsy samples of the bone marrow in case 1 revealed hypercellularity as well as a large number of immature lymphoblastic cells similar in shape to cells in the peripheral blood. The characteristic morphological features of peripheral blood and bone marrow samples in case 2 were small lymphocytes. Thus, the dogs were tentatively diagnosed with acute lymphoblastic leukemia (ALL) and chronic lymphocytic leukemia (CLL), respectively. After diagnosis, the CLL patient was administered chlorambucil and prednisolone therapy. Due to its similarity to human leukemia, the canine leukemia model provides a valuable model for research into human leukemia.
Anemia ; Animals ; Anorexia ; Biopsy ; Blood Cell Count ; Bone Marrow ; Cattle ; Child ; Chlorambucil ; Chromatin ; Depression ; Diagnosis ; Dogs* ; Humans ; Leukemia ; Leukemia, Lymphocytic, Chronic, B-Cell* ; Leukocytosis ; Lymph Nodes ; Lymphocytes ; Lymphocytosis ; Lymphoma ; Physical Examination ; Precursor Cell Lymphoblastic Leukemia-Lymphoma* ; Prednisolone ; Radiography ; Splenomegaly ; Thrombocytopenia ; Ultrasonography

Chronic lymphocytic leukemia (CLL) is a unique indolent B-cell leukemia which is rare in Korea. Many patients with early stage CLL do not require immediate treatment, while those with advanced stage or symptoms need systemic chemotherapy. As our understanding about the pathophysiology of CLL increases, significant advances have been achieved in the treatment of this disease. Modern molecular genetics have been revealing remarkable heterogeneity of various genetic alterations and the corresponding prognostic stratification in CLL. The treatment of CLL had been developed from nitrogen mustard alkylating agent like chlorambucil to combination therapy including purine analogues like pentostatin and fludarabine until early 2000s. Since the introduction of targeted agent like anti-CD20 and anti-CD52 monoclonal antibodies in the treatment of CLL, the treatment outcome of CLL has leaped further. In conclusion, one of the current standard regimens in patients with untreated CLL is the combination of rituximab, cyclophosphamide and fludarabine. We recently passed the entrance for the era of targeted therapy, and are exploring various new agents and their combinations.
Antibodies, Monoclonal ; Antibodies, Monoclonal, Murine-Derived ; Chlorambucil ; Cyclophosphamide ; Humans ; Korea ; Leukemia, B-Cell ; Leukemia, Lymphocytic, Chronic, B-Cell ; Mechlorethamine ; Molecular Biology ; Pentostatin ; Population Characteristics ; Prognosis ; Purines ; Treatment Outcome ; Vidarabine ; Rituximab

Healthcare workers are exposed to a variety of chemical agents used in many different areas and purposes. The chemicals could cause health problems to healthcare workers using them. Glutaraldehyde is a kind of disinfectant and used for endoscopes, catheters, and many kinds of operating apparatus. It may cause allergic contact dermatitis. Formaldehyde is another disinfectant and can be used for fixing tissues. Formaldehyde was classified to a Group 1 carcinogen by IARC and it may cause lung or nasal cancer. Ethylene Oxide gas is the most popular disinfectant these days and may be applied to many health care sets or linens. EO gas may cause allergic contact dermatitis and breast cancer or leukemia. It is also classified as Group 1 carcinogen despite limited evidence for human cancers. Anesthetics are related to genotoxicities, sister chromatid exchange, and might be related to spontaneous abortion, stillbirth or birth defects. Some of the anti-neoplastic drugs such as Busulfan, Chlorambucil, cyclophosphamide, melphalan are Group 1 carcinogens. They could cause nausea, pruritus, or decreasing leukocytes or platelets. Other miscellaneous chemical agents are heavy metals such as elementary mercury or lead and organic solvents such as toluene, xylene and acetone. Although some of these chemical agents including EO gas have occasionally exceeded to permissible level, air levels of most above chemicals in Korean hospitals were relatively low. However, we have to make every effort to reduce the exposure level of these chemicals.
Abortion, Spontaneous ; Acetone ; Anesthetics ; Bedding and Linens ; Blood Platelets ; Breast Neoplasms ; Busulfan ; Carcinogens ; Catheters ; Chlorambucil ; Congenital Abnormalities ; Cyclophosphamide ; Delivery of Health Care ; Dermatitis, Allergic Contact ; Endoscopes ; Ethylene Oxide ; Ethylenes ; Female ; Formaldehyde ; Glutaral ; Humans ; Leukemia ; Leukocytes ; Lung ; Melphalan ; Metals, Heavy ; Nausea ; Nose Neoplasms ; Pregnancy ; Pruritus ; Sister Chromatid Exchange ; Solvents ; Stillbirth ; Toluene ; Xylenes

Cold agglutinin disease (CAD) is an autoimmune hemolytic anemia (AIHA) induced by cold antibodies. CAD constitutes 16~32% of AIHA cases and the causative cold autoantibodies are commonly specific against blood group I or i antigens. CAD is closely related to lymphoid neoplasia and infections such as Mycoplasma and Epstein-Barr virus (EBV). Primary CAD has a tendency to develop into malignant lymphoma over its course. We experienced a case of small lymphocytic lymphoma during the treatment of primary CAD over 11 years. The patient was a 67-year-old man who complained of a neck mass. Node biopsy revealed diffuse neoplastic proliferation of small monotonous lymphoid cells with polygonal or oval nuclei;these cells were CD20- and CD5-positive. Follow-up chest and neck computed tomography after treatment with chlorambucil and prednisolone showed partial resolution and stable disease status for over 2 years. We report a case of small lymphocytic lymphoma that developed in a patient with long-standing cold agglutinin disease for 11 years and review the literature.
Aged ; Anemia ; Anemia, Hemolytic, Autoimmune ; Antibodies ; Autoantibodies ; Biopsy ; Chlorambucil ; Cold Temperature ; Follow-Up Studies ; Herpesvirus 4, Human ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell ; Lymphocytes ; Lymphoma ; Mycoplasma ; Neck ; Prednisolone ; Thorax

It is generally accepted that seroconversion of hepatitis B virus (HBV) surface antigen (HBsAg) to an antibody to HBsAg (anti-HBs) indicates clearance of HBV. Here we report a case of severe hepatitis that manifested during chemotherapy in a female patient with chronic lymphocytic leukemia (CLL) who had been initially seronegative for HBsAg and seropositive for anti-HBs. The patient received chlorambucil and prednisolone for the treatment of CLL. After 6 months the serum levels of aminotransferases were increased, and HBsAg and HBV DNA were present in serum. Lamivudine was administered immediately after confirming the HBV reactivation, which considerably improved jaundice and aminotransferase levels after 3 weeks. The patient was able to resume the chemotherapy whilst continuing lamivudine treatment. This case report highlights the need for physicians to be aware of the potential risk of HBV reactivation even in an HBsAg-negative person but with detectable anti-HBc and/or anti-HBs, underscoring the need for future studies that explore the role of antiviral prophylaxis in this setting.
Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Chlorambucil/*therapeutic use ; Female ; Hepatitis B/*diagnosis/virology ; Hepatitis B Antibodies/*blood/immunology ; Hepatitis B Surface Antigens/*blood/immunology ; Hepatitis B virus/isolation & purification/physiology ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/complications/*drug therapy ; Prednisolone/*therapeutic use ; Virus Activation

OBJECTIVETo explore the possible association between activation of rat microsomal glutathione S-transferase 1 (mGST1) and chlorambucil toxicity on selected cancer cell lines.

METHODSHepatic microsomes were prepared from male Sprague-Dawley rats and washed to remove cytosolic contamination. mGST1 was purified and its activity was measured. PC-3, K562, HepG2 and P388D1 cell lines were exposed to chlorambucil (CHB) alone or to CHB with mGST1 at concentrations of 0 ~ 100 micromol/L for 8, 24, 48, 72 h. Cytotoxic effects of CHB were determined by cell growth inhibition (MTT assay), mitochondrial transmembrane potential (DeltaPsim), and fluorescence morphological examination (AO/EB staining).

RESULTSThe decreased cytotoxic effects of CHB on the cell lines altered by mGST1 were demonstrated in concentration- and time-dependant manners. The CHB-induced apoptosis on PC-3 and K562 cell lines altered by mGST1 was confirmed using DeltaPsim examination, JC-1 or AO/EB staining.

CONCLUSIONmGST1 can reduce the cytotoxic effects of CHB in selected cancer cell lines.

Animals ; Antineoplastic Agents, Alkylating ; metabolism ; pharmacology ; Apoptosis ; drug effects ; Cell Line, Tumor ; Cell Survival ; drug effects ; Chlorambucil ; metabolism ; pharmacology ; Dose-Response Relationship, Drug ; Glutathione Transferase ; isolation & purification ; metabolism ; Humans ; K562 Cells ; Microsomes, Liver ; enzymology ; Rats ; Rats, Sprague-Dawley

Generalized granuloma annulare (GGA) is an uncommon type of granuloma annulare. It is frequently characterized by chronicity and unresponsiveness to a number of therapeutic modalities. A variety of systemic treatment modalities for GGA have been tried, including PUVA, dapsone, hydroxychloroquine, systemic corticosteroids, niacinamide, vitamin E and chlorambucil. However, their efficacy was not very encouraging. We present a case of GGA which showed a satisfactory response to isotretinoin. To conclude, isotretinoin may be considered as treatment for GGA in patients with unacceptable cosmetic disfigurements or symptoms.
Adrenal Cortex Hormones ; Chlorambucil ; Dapsone ; Granuloma Annulare* ; Granuloma* ; Humans ; Hydroxychloroquine ; Isotretinoin* ; Niacinamide ; Vitamin E ; Vitamins

In Behcet's disease, thrombocytopenia has rarely been reported in association with the hemolytic uremic syndrome, thrombotic thrombocytopenic purpura or in association with cyclosporine or chlorambucil in the treatment of ocular inflammatory disease and meningoencephalitis. In this paper we report a case of thrombocytopenia in a 33-year-old female with Behcet's disease who has taken no medications for three years. After history taking, physical examination, routine laboratory and bone marrow examination, we diagnosed her case as idiopathic thrombocytopenic purpura (ITP). She recovered with high dose steroid treatment. To our knowledge, this is the first report having ITP in a patient with Behcet's disease.
Adult ; Bone Marrow Examination ; Chlorambucil ; Cyclosporine ; Female ; Hemolytic-Uremic Syndrome ; Humans ; Meningoencephalitis ; Physical Examination ; Purpura, Thrombocytopenic, Idiopathic* ; Purpura, Thrombotic Thrombocytopenic ; Thrombocytopenia