Chemotherapy-induced cancer cell secretomes promote resistance due, in part, to a predominant glycolytic energy metabolism, which drives aggressive cancer cell proliferation. However, the characterization of these secretomes and the molecular events that associate them with acquired drug resistance remain poorly understood. In this study, we show that secretomes of cancer cells with high-level paclitaxel resistance stimulated cell proliferation and suppressed drug-induced apoptosis of drug-sensitive cells. We also found that drug (docetaxel)-stimulated induction of interferon-α (IFN-α), IFN-λ and tumor necrosis factor-α (TNF-α) release in drug-sensitive cells was lowered by these secretomes. The promotion of cell proliferation by paclitaxel-resistant (PacR) cancer cell secretomes was associated, in part, with an increase in S phase of the cell cycle and downregulation of the cell death pathway that supports escape from apoptosis. In addition, we also found that the regulation of targeted glycolysis in PacR cancer cells alters the effects of the secretomes on cell growth, apoptosis, ATP generation and acquired drug resistance. Further study revealed that the deletion of FOXO3a transcription exacerbates glycolytic shift-induced apoptosis by rescuing TRAIL expression. By generating a docetaxel–cross-resistant PacR cancer cell line (PacR/DCT), we further clarified the role of FOXO3a in glycolysis-associated mediation of P-glycoprotein/ABCB1 hyperactivity that induces docetaxel cross-resistance. These findings suggest that suppression of the cellular energy supply by targeting glycolysis may inhibit the multiplicity of acquired chemotherapy resistance. Therefore, the therapeutic inhibition of FOXO3a might direct glycolysis to induce apoptosis and overcome multidrug resistance in cancer cells.
Adenosine Triphosphate ; Apoptosis* ; Cell Cycle ; Cell Death ; Cell Line ; Cell Proliferation ; Down-Regulation ; Drug Resistance ; Drug Resistance, Multiple ; Drug Therapy ; Energy Metabolism ; Glycolysis ; Necrosis ; Negotiating ; Paclitaxel ; S Phase ; United Nations*

Red cell antigens, A, B, and H can be weakened or lost especially in patients with hematologic malignancies. We report a 42-year-old female patient with acute myeloid leukemia, who showed loss of A antigen on her red cells. She showed the persistence of leukemia in spite of three cycles of induction chemotherapy. Her ABO blood group showed a discrepancy: the cell type was O and the serum type was A. Adsorption/elution test could not identify the presence of A antigen on her red cells, and the test for A and B transferases was negative. ABO genotyping using PCR/restriction fragment length polymorphism and sequencing of exons 6 and 7 of the ABO gene demonstrated 467 C>T substitution in exon 7 and confirmed the genotype of A102/O01. She was transfused with leukapheresis products collected from donors with blood group A, but expired of severe sepsis. This is the first Korean case, in which red cell A antigen loss was genetically proven using sequencing, and underscores the necessity of ABO genotyping to solve the ABO discrepancy and to transfuse effectively.
Adult ; Exons ; Female ; Genotype ; Hematologic Neoplasms ; Humans ; Induction Chemotherapy ; Leukapheresis ; Leukemia ; Leukemia, Myeloid, Acute ; Sepsis ; Tissue Donors ; Transferases

Variant Burkitt-type translocation, t(8;22)(q24;q11), is very rare in plasma cell myeloma. We report a 51-year-old male patient with plasma cell myeloma, who showed t(8;22) (q24;q11). He suffered from pelvic pain for two months, and showed IgG, lambda type of monoclonal gammopathy (5.14 g/dL; 49.9% of protein). His bone marrow examination showed increased plasma cells (66.9% of all nucleated cells). Plasma cells (74.9% of all nucleated cells) and monoclonal spike (3.38 g/dL; 42.2%) persisted after three cycles of thalidomide and dexamethasone. Cytogenetic analysis showed complex chromosomal abnormalities: 44,XY,-1,t(2;5)(q33;q13),add(8)(q24.1),t(8;22)(q24.1;q11.2),add(10) (p15), der(11)t(1;11)(q21;p11.2),del(12)(p11.2p13),-13,-14,add(14)(q32),der(15)t(1;15)(p2 2;p11.2),-16,add(17)(q11.2),+21,+1-3mar[cp6]/46,XY[19]. To the best of our knowledge, this is the first report on plasma cell myeloma with a variant Burkitt-type t(8;22)(q24;q11) in the Korean patient. A review of 11 such cases in the literature, including the present case, implicated that plasma cell myeloma with t(8;22)(q24;q11) might be related to advanced stage and poor prognosis.
Bone Marrow Examination ; Cytogenetic Analysis ; Dexamethasone ; Humans ; Immunoglobulin G ; Male ; Middle Aged ; Multiple Myeloma ; Paraproteinemias ; Pelvic Pain ; Plasma ; Plasma Cells ; Prognosis ; Thalidomide

Aged ; Cardiac Catheters ; Combined Modality Therapy ; Coronary Restenosis ; therapy ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Paclitaxel ; administration & dosage ; therapeutic use ; Percutaneous Coronary Intervention ; instrumentation ; Stents ; Treatment Outcome ; Tubulin Modulators ; administration & dosage ; therapeutic use

Mucormycosis is a fungal infection, which is difficult to treat due to its rapid dissemination and low susceptibility to anti-fungal agents. Peritonitis preceded by gastrointestinal mucormycosis is very rare, and only a few cases have been reported. We present a case of peritonitis and disseminated mucormycosis caused by Mucor circinelloides in an immunocompromised patient. A 59-year-old man, diagnosed with nodal marginal zone B-cell lymphoma, was diagnosed with liver failure due to severe septic shock. A white, woolly cotton-like growth, which was consistent with that of Mucor species, was isolated from ascites and sputum specimens. Targeted DNA sequencing confirmed the isolate as M. circinelloides with 100% identity. Despite anti-fungal treatment, the patient died after four days. This is a rare case of peritonitis and disseminated mucormycosis that was probably preceded by gastrointestinal mucormycosis caused by M. circinelloides, as determined by molecular methods. Accurate and rapid identification of mold using molecular methods might be necessary for early treatment in critical cases, and more cases should be clinically evaluated further.

BACKGROUND/AIMS: Helicobacter pylori (H. pylori) infection appears to subvert the human iron regulatory mechanism and thus upregulates hepcidin, resulting in unexplained iron-deficiency anemia (IDA). We evaluated serum prohepcidin levels before and after eradication of H. pylori in IDA patients to assess whether it plays a role in IDA related to H. pylori infection. METHODS: Subjects diagnosed with unexplained IDA underwent upper gastrointestinal endoscopy and colonoscopy to confirm H. pylori infection and to exclude gastrointestinal bleeding. Blood was sampled before treatment to eradicate H. pylori and again 1 month later. Serum prohepcidin levels were measured using a commercial enzyme-linked immunosorbent assay kit. RESULTS: Serum prohepcidin levels decreased significantly after oral iron replacement combined with H. pylori eradication (p = 0.011). The reduction ratio of serum prohepcidin levels after the treatment did not differ among the combined oral iron replacement and H. pylori eradication groups, the H. pylori eradication only group, and the iron replacement only group (p = 0.894). CONCLUSIONS: Serum prohepcidin levels decrease after both H. pylori eradication and oral iron administration, with improvement in IDA. Serum concentration of prohepcidin is related to the anemia status, rather than to the current status of H. pylori infection, in IDA patients.
Administration, Oral ; Adult ; Aged ; Anemia, Iron-Deficiency/*blood/drug therapy/*microbiology ; Antimicrobial Cationic Peptides/*blood ; Endoscopy, Gastrointestinal ; Female ; Follow-Up Studies ; Helicobacter Infections/*blood/*complications/pathology ; *Helicobacter pylori ; Humans ; Iron/administration & dosage ; Male ; Middle Aged ; Prospective Studies ; Protein Precursors/*blood ; Severity of Illness Index

BACKGROUND: CD4+CD25+ regulatory T-cells (Tregs) play a critical role in immune responses. We explored the status of Tregs in neoplastic and autoimmune hematologic diseases. We also evaluated the technical aspects of Treg measurement in terms of sample type and detection markers. METHODS: A total of 68 subjects were enrolled: 11 with AML, 8 with MDS, 10 with autoimmune diseases, and 39 controls. Tregs were analyzed in peripheral blood (PB) and bone marrow (BM) samples from each subject. Flow cytometry and the Human Regulatory T cell Staining Kit (eBioscience, USA) for CD4, CD25, and FoxP3 (forkhead box P3) were used. RESULTS: The CD4+CD25high/CD4 and CD4+CD25highFoxP3+/CD4 populations were significantly correlated (P<0.0001). The AML and high-risk MDS groups had significantly larger CD4+CD25high/CD4 and CD4+CD25highFoxP3+/CD4 populations in PB than the autoimmune (P=0.007 and 0.012, respectively) and control groups (P=0.004 and 0.006, respectively). Comparable findings were observed in BM. The CD4+CD25highFoxP3+/CD4 population was significantly larger in PB than in BM (P=0.0003). CONCLUSIONS: This study provides comparison data for Tregs in AML, MDS, and autoimmune hematologic diseases, and would be helpful for understanding the different immunologic bases of various hematologic diseases. Treg measurement using CD4, CD25, and/or FoxP3 in PB rather than in BM seems to be practical for routine hematologic purposes. Large-scale analysis of the diagnostic role of Treg measurement is needed.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Autoimmune Diseases/diagnosis/immunology ; Bone Marrow Cells/cytology ; Female ; Flow Cytometry ; Forkhead Transcription Factors/*metabolism ; Hematologic Diseases/*diagnosis/immunology ; Humans ; Interleukin-2 Receptor alpha Subunit/*metabolism ; Leukemia, Myeloid, Acute/diagnosis/immunology ; Leukocytes, Mononuclear/cytology ; Male ; Middle Aged ; Myelodysplastic Syndromes/diagnosis/immunology ; T-Lymphocytes, Regulatory/immunology/*metabolism

Although lead intoxication is commonly mentioned as a cause of sideroblastic anemia, no well-documented case exists in the literature. We encountered a patient with sideroblastic anemia caused by lead-containing herbal medicine. A 34-year-old woman was admitted to our hospital with abdominal pain. She had taken herbal medicine for her general health. Anemia, hyperbilirubinemia, and elevated lactic dehydrogenase were found from the laboratory data. Bone marrow biopsy showed pathological ringed sideroblasts. Her serum level of lead was high and the lead content of the tablet was higher than permitted. We diagnosed her with sideroblastic anemia secondary to lead poisoning caused by herbal medicine. We stopped her from taking herbal medicine and she gradually recovered from anemia.
Abdominal Pain ; Adult ; Anemia ; Anemia, Sideroblastic ; Biopsy ; Bone Marrow ; Female ; Herbal Medicine ; Humans ; Hyperbilirubinemia ; Lead Poisoning ; Oxidoreductases

We report on a case of malignant pleural effusion as initial metastatic presentation of occult gastric cardia cancer in a young woman. To the best of our knowledge, this is the first report of gastric adenocarcinoma metastasized to pleura as an initial presentation. Location of cardia and signet ring cell histology may contribute to the manifestation. Utilization of positron emission tomography-computed tomography was helpful for proper diagnosis. For patients with such distinct clinical presentations, it would be appropriate to consider gastric cancer as one of the possible primary sites.
Adenocarcinoma ; Carcinoma, Signet Ring Cell ; Cardia* ; Diagnosis* ; Electrons ; Female ; Humans ; Neoplasm Metastasis* ; Pleura ; Pleural Effusion, Malignant ; Positron-Emission Tomography ; Stomach Neoplasms

Chemotherapy-induced alopecia and hair loss can be stressful in patients with cancer. The hair grows back, but sometimes the hair tends to stay thin. Therefore, understanding mechanisms regulating hair regeneration may improve the management of chemotherapy-induced alopecia. Previous studies have revealed that chemotherapeutic agents induce a hair follicle vascular injury. As hair growth is associated with micro-vessel regeneration, we postulated that the stimulation of angiogenesis might enhance hair regeneration. In particular, mice treated with 5-fluorouracil (5-FU) showed delayed anagen initiation and reduced capillary density when compared with untreated controls, suggesting that the retardation of anagen initiation by 5-FU treatment may be attributed to the loss of perifollicular micro-vessels. We investigated whether the ETS transcription factor ETV2 (aka ER71), critical for vascular development and regeneration, can promote angiogenesis and hair regrowth in a 5-FU-induced alopecia mouse model. Tie2-Cre; Etv2 conditional knockout (CKO) mice, which lack Etv2 in endothelial cells, presented similar hair regrowth rates as the control mice after depilation. Following 5-FU treatment, Tie2-Cre; Etv2 CKO mice revealed a significant reduction in capillary density, anagen induction, and hair restoration when compared with controls. Mice receiving lentiviral Etv2 injection after 5-FU treatment showed significantly improved anagen induction and hair regrowth. Two-photon laser scanning microscopy revealed that enforced Etv2 expression restored normal vessel morphology after 5-FU mediated vessel injury. Our data suggest that vessel regeneration strategies may improve hair regrowth after chemotherapeutic treatment.