M-S Dai

Acute respiratory distress syndrome following intrathecal methotrexate administration : a case report and review of literature

Abstract Acute Respiratory distress syndrome (ARDS) is a rare complication following intrathecal (IT) injection of methotrexate (MTX) in adult acute lymphoblastic leukemia (ALL) patients. A 19-year-old man with ALL developed strikingly acute respiratory failure during central nervous system (CNS) prophylaxis with IT MTX administration and cranial irradiation. Histopathologic study of the lungs revealed a pattern of diffuse alveolar damage with interstitial cellular infiltration. His symptoms were relieved soon following treatment with corticosteroids and the pulmonary infiltrates resolved gradually. Pulmonary symptoms did not recur as he was continuously treated with oral corticosteroids.

Stenotrophomonas maltophilia septicemia with pyomyositis in a chemotherapy-treated patient

Pyomyositis is a rare complication of chemotherapy. A 35-year-old male patient with myelodysplastic syndrome developed Stenotrophomonas maltophilia bacteremia shortly after chemotherapy, and Stenotrophomonas maltophilia-related pyomyositis was encountered after recovery from neutropenia. He recovered completely after surgical drainage and a protracted course of antibiotic treatment. It is postulated that subclinical myopathy, immunosuppression secondary to the malignancy, or chemotherapeutic drugs may predispose to pyomyositis. Early recognition of this unusual complication in a cancer patient undergoing chemotherapy can prevent further catastrophes.

Suppurative salmonella thyroiditis in a patient with chronic lymphocytic leukemia.

We describe an 82-year-old man with undiagnosed chronic lymphocytic leukemia (CLL) who presented with acute swelling of the thyroid goiter. Subsequent thyroid aspirate and blood culture yielded group B Salmonella thyroid abscess with septicemia. Infectious complications are the major cause of morbidity and mortality in patients with CLL since most of them can be timely detected and few can arise from innocent-looking lesions.

Lymphoma of bone with initial presentation as a calvarial mass

Abstract A 21-year-old man was examined for a right frontal skull mass that had been present for 4 months. Excision biopsy of the mass revealed diffuse large B-cell lymphoma. Subsequent studies showed right preauricular lymphadenopathy but no systemic involvement. The patient was treated with six courses of CHOP (cyclophosphamide, adriamycin, vincristine, and prednisolone) with adjuvant whole brain irradiation and achieved a complete remission.

Abstract P1-03-08: Tartrate-resistant acid phosphatase (TRAcP) dependent polarization of breast cancer-promoting macrophages

Background: Breast cancer associated macrophages often promote tumor growth and metastasis by conditioning the tumor microenvironment and suppressing adaptive immune responses. Tartrate-resistant acid phosphatase (TRACP) is a novel serum biomarker associated with systemic macrophage burden in a variety of chronic inflammatory diseases and is strongly expressed by tumor-associated macrophages. We tested the hypothesis that TRACP is required for M2 macrophage polarization. Methods: Macrophage cell lines were polarized in vitro and tested for TRACP, iNOS and Arg-1 expression and their ability to promote or repress breast cancer cell growth and invasion in vitro and in vivo. A novel TRACP deficient, Acp5 mutant mouse was used as a macrophage source and as a breast cancer host to confirm a role for TRACP for macrophages to support cancer growth. Results: TRACP was up-regulated in concert with M2 polarization and down-regulated in M1 polarized cells. TRACP expression correlated with macrophage promotion of tumor growth and invasion in vitro. Although TRACP-deficient macrophages could be induced to express Arg-1 when stimulated with IL-4 plus IL-13 (M2 phenotype), the TRACP deficient macrophages behaved like M1 cells suppressing tumor growth and invasion compared to than WT cells. Tumor xenografts grew slower in primary subcutaneous grafts and metastasized less extensively in intravenous grafts in TRACP deficient mice compared to WT. Furthermore, the tumor metastatic patterns could be reversed in WT animals by co-grafting TRACP-deficient macrophages and in TRACP deficient hosts by co-grafting WT macrophages. Conclusions: TRACP expression is normally a phenotypic marker for alternatively activated macrophages, but not necessary for expression of Arg-1. In a host environment of TRACP deficiency, Arg-1 positive macrophages can be generated by cytokine stimulation in vitro and by tumor in vivo, however, TRACP deficiency still conveyed a tumor suppressive phenotype in cell based studies and in intact animals. TRACP plays a role in functional polarization of M2 macrophages and their ability to promote breast cancer growth and metastasis. Citation Format: Dai M-S, Janckila A, Lo H-C, Wu C-C, Chao T-Y, Yu J-C. Tartrate-resistant acid phosphatase (TRAcP) dependent polarization of breast cancer-promoting macrophages. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-03-08.

Abstract P4-04-07: Tartrate-resistant Acid Phosphatase (TRAcP)-Expressed Tumor-Associated Macrophages Promote Breast Cancer Progression

Purpose: Tumor-associated macrophages (TAMs) can promote or dampen breast cancer progression, depending on phenotypic changes within the cancer microenvironment. Two contrasting activation states were described in the literature: the M1 anti-tumoral and M2 pro-tumoral subtype of TAMs. In clinical observation, we analyzed the TRAcP expression in breast cancer TAM and correlated to patient9s chemotherapy responses and survival. In animal models, we aim to investigate the tumor-promoting or inhibiting properties among tartrate-resistant acid phosphatase (TRAcP) expressed TAMs. Methods: TRAcP expression, T lymphocytes, and other macrophage relevant markers were determined by immunohistochemical staining in the human breast cancer tissue from the patients before neoadjuvant chemotherapy. The expression of TRAcP within the TAMs were calculated and correlated to the patient9s chemotherapy responsiveness and outcome. The polarized M1/M2 macrophages and breast cancer hematogenous metastasis were created in the animal model. Activated macrophages from TRAcP+/+ or TRAcP−/− mice were injected with JC (Balb/c breast cancer) cells in the metastatic model. Results: The presence of Foxp3+ regulatory T cell (Treg) correlates to the tumor proliferation (Ki-67 and Her2 expression) and higher Foxp3+ Treg prevalence and tumor Ki-67 expression inferred poorer chemotherapy response. TRAcP staining within the CD68+ macrophages were observed with better chemotherapy response. In animal model, M2 polarized macrophages have higher TRAcP expression, promote breast cancer metastasis, and attract Treg infiltrating in tumor, consistent with the clinical observation. Conclusion: TRAcP-expressing TAMs, representing M2-polarized macrophage, demonstrat local tumor-promoting and immune-suppressive effects, and chemotherapy resistance. TRAcP expression within TAM can be a potential prognostic marker for breast cancer. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-04-07.