Triple negative cancer

lymphoid tissue can be detected [14]. In contrast, increased numbers of lymphocytes are frequently detectable around and within breast cancers [15-18]. The clinical significance of TILs in breast cancer is still controversial. In some studies, TILs were associated with unfavorable characteristics such as high grade tumors, estrogen receptor negativity, basal-like molecular subtype as well as her2/neu positive tumors [19,20]. High CD4⁺ and CD8⁺ lymphocytic infiltration has been associated with positive lymph node status as well as worse overall survival [21]. Furthermore, in early stage breast cancer, CD8⁺ lymphocytic infiltration has been suggested to correlate with lymph node involvement [22]. Other groups, however, have shown that breast cancers with increased TIL number display a better prognosis in comparison with breast cancers with lesser lymphocyte infiltration [23], as also confirmed by data from our institution for CD8⁺ TILs in the ER negative subgroup [24]. Additionally, high TIL counts may represent an independent predictor of response to neo-adjuvant chemotherapy [25]. Notably, infiltration by FOXP3⁺ lymphocytes in breast cancer has been proposed to represent an independent unfavorable prognostic factor, especially in the nodal positive subgroup [26] and to correlate with tumor invasiveness [27]. In contrast, a complete clinical response has been suggested to be associated with disappearance of tumor infiltrating FOXP3⁺ T-cells during treatment [28].

While the clinical significance of TILs is controversial, their distribution within stromal and intratumoral compartments in breast cancers is largely unknown. Furthermore, T-cell infiltration in different histological subtypes as well as the occurrence of IL-17⁺ lymphocytes in breast cancer tissue has not been reported to date. Here, we addressed these issues by using a tissue microarray (TMA) including a large number (> 1000) of breast cancers stratified according to ductal and lobular histological subtypes. By taking advantage of a comprehensive clinical follow-up database, numbers of CD4⁺, FOXP3⁺ and IL-17⁺ TILs and their occurrence in different tumor compartments was correlated with clinico-pathological features and survival data.

Chagas Disease its treatment/ Th2,Th1 and its side effects

subject: Current status of Chagas disease chemotherapy
object_opposite: Chagas disease current treatment / Benznidazole and nifurtimox /side effects/American trypanosomiasis (Chagas' disease) is an endemic parasitic disease afflicting more than 20 million persons in Latin America. Two drugs are currently being used for treatment of the acute phase of Chagas' disease: 4-[(5-nitrofurfurylidene)amino-3-methylthiomorpholine-1,1-di oxide] (Nifurtimox; Nfx) and (N-benzl-2-nitro-1-imidazole acetamide) (Benznidazole; Bz). Nfx and Bz have serious undesirable effects, which have been reported during their clinical use, including anorexia and weight loss, nausea and vomiting, nervous excitation, insomnia, psyche depressions, convulsions, vertigo, headache, sleepiness, myalgias, arthralgias, loss of balance, disorientation, forgetfulness, paresthesias, adynamia, acoustic phenomena, peripheral neuropathies, gastralgia, mucosal edema, hepatic intolerance, skin manifestations, and intolerance to drinking alcohol. Effects in the central and peripheral nervous system of Nfx were also reproduced in animals/Biomed Environ Sci. 1988 Jun;1(1):19-33/ Toxic effects of nifurtimox and benznidazole, two drugs used against American trypanosomiasis (Chagas' disease)/Castro JA1, Diaz de Toranzo EG.
misc: Chagas disease affects 7.7 million people and 28 million people are at risk of acquiring the disease in 15 endemic countries of Latin America. Benznidazole and nifurtimox are drugs that have been used to treat the disease. However, both drugs induce severe side effects. Treatment with benznidazole has been recommended for the acute phase (0-4 months after infection), recent chronic phase (children 0-14 years of age, treated 4 months after infection) and congenital infection. Average cure rates for Chagas disease patients obtained from clinical trials were 97.9% (congenital infection, treatment performed 0-6 months of age), 71.5% (acute phase), 57.6% (recent chronic phase, children 0-13 years of age) and 5.9% (late chronic phase, great majority of patients between 15 and 69 years of age). Clinical evidence about the capacity of antiparasitic treatment to avoid, stop or revert heart pathology in indeterminate and cardiac chronic patients is contradictory. The investigation of novel therapeutic strategies against Chagas disease remains a priority in the research of tropical diseases. Unfortunately, Chagas disease remains neglected in the formulation of strategies toward control of this disease. This article focuses on current therapeutic approaches to Chagas disease/2nd American trypanosomiasis (Chagas' disease) is an endemic parasitic disease afflicting more than 20 million persons in Latin America. Two drugs are currently being used for treatment of the acute phase of Chagas' disease: 4-[(5-nitrofurfurylidene)amino-3-methylthiomorpholine-1,1-di oxide] (Nifurtimox; Nfx) and (N-benzl-2-nitro-1-imidazole acetamide) (Benznidazole; Bz). Nfx and Bz have serious undesirable effects, which have been reported during their clinical use, including anorexia and weight loss, nausea and vomiting, nervous excitation, insomnia, psyche depressions, convulsions, vertigo, headache, sleepiness, myalgias, arthralgias, loss of balance, disorientation, forgetfulness, paresthesias, adynamia, acoustic phenomena, peripheral neuropathies, gastralgia, mucosal edema, hepatic intolerance, skin manifestations, and intolerance to drinking alcohol. Effects in the central and peripheral nervous system of Nfx were also reproduced in animals. Signs of testicular and ovarian injury were reported for both Nfx and Bz, the effects of Bz being in general less intense than those of Nfx. Both drugs evidenced mutagenicity. In light of the present knowledge about the toxicity of Nfx and Bz, further studies on the mutagenic, teratogenic, carcinogenic, and reproductive effects of both drugs are recommended. Lack of information is particularly serious for Bz. Studies on Nfx and Bz biotransformation, activation to reactive metabolites, and potential mechanisms for their toxic effects were analyzed. Risk-benefit considerations of the use of Nfx and Bz were made and an analysis of the need for research on Chagas' disease chemotherapy was also performed
author_year: Guedes PM/Silva GK/Gutierrez FR/Silva JS/ 2011
journal_volume_page: Expert Rev Anti Infect Ther./ May;9(5):609-20