Cytokines in cancer pathogenesis and cancer therapy

[1]  G. Forni,et al.  Helper strategy in tumor immunology: Expansion of helper lymphocytes and utilization of helper lymphokines for experimental and clinical immunotherapy , 1988, Cancer and Metastasis Reviews.

[2]  R. Zinkernagel On natural and artificial vaccinations. , 2003, Annual review of immunology.

[3]  Wancai Yang,et al.  γδ T Cells Provide an Early Source of Interferon γ in Tumor Immunity , 2003, The Journal of experimental medicine.

[4]  Hideo Negishi,et al.  Integration of interferon-α/β signalling to p53 responses in tumour suppression and antiviral defence , 2003, Nature.

[5]  G. Dranoff,et al.  CD1d-restricted T cells regulate dendritic cell function and antitumor immunity in a granulocyte–macrophage colony-stimulating factor-dependent fashion , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[6]  Thomas A. Davis,et al.  Cancer regression and autoimmunity induced by cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[7]  F. Alt,et al.  Deficiencies of GM-CSF and Interferon γ Link Inflammation and Cancer , 2003, The Journal of experimental medicine.

[8]  D. Hanahan,et al.  Immune Enhancement of Skin Carcinogenesis by CD4+ T Cells , 2003, The Journal of experimental medicine.

[9]  Piero Musiani,et al.  Nonredundant roles of antibody, cytokines, and perforin in the eradication of established Her-2/neu carcinomas. , 2003, The Journal of clinical investigation.

[10]  Thomas Davis,et al.  Biologic activity of cytotoxic T lymphocyte-associated antigen 4 antibody blockade in previously vaccinated metastatic melanoma and ovarian carcinoma patients , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[11]  Ken Jung,et al.  Melanoma inhibitor of apoptosis protein (ML-IAP) is a target for immune-mediated tumor destruction , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[12]  A. Davidoff,et al.  Local and systemic effects of an allogeneic tumor cell vaccine combining transgenic human lymphotactin with interleukin-2 in patients with advanced or refractory neuroblastoma. , 2003, Blood.

[13]  Mark M. Davis,et al.  Chronic myelogenous leukemia shapes host immunity by selective deletion of high-avidity leukemia-specific T cells. , 2003, The Journal of clinical investigation.

[14]  Y. Iwakura,et al.  IL-1 is required for tumor invasiveness and angiogenesis , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[15]  D. Neuberg,et al.  Vaccination with irradiated autologous tumor cells engineered to secrete granulocyte-macrophage colony-stimulating factor augments antitumor immunity in some patients with metastatic non-small-cell lung carcinoma. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[16]  George Coukos,et al.  Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. , 2003, The New England journal of medicine.

[17]  V. Weinberg,et al.  Prostate-specific antigen kinetics as a measure of the biologic effect of granulocyte-macrophage colony-stimulating factor in patients with serologic progression of prostate cancer. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[18]  F. Hodi,et al.  MUC1-like tandem repeat proteins are broadly immunogenic in cancer patients. , 2003, Cancer immunity.

[19]  F. Belardelli,et al.  ICSBP Is Essential for the Development of Mouse Type I Interferon-producing Cells and for the Generation and Activation of CD8α+ Dendritic Cells , 2002, The Journal of experimental medicine.

[20]  S. Pawlowski,et al.  Elimination of colon cancer in germ-free transforming growth factor beta 1-deficient mice. , 2002, Cancer research.

[21]  R. Schreiber,et al.  Cancer immunoediting: from immunosurveillance to tumor escape , 2002, Nature Immunology.

[22]  S. Kaneko,et al.  Prevention of Hepatocellular Carcinoma Development Associated with Chronic Hepatitis by Anti-Fas Ligand Antibody Therapy , 2002, The Journal of experimental medicine.

[23]  A. Diefenbach,et al.  The innate immune response to tumors and its role in the induction of T‐cell immunity , 2002, Immunological reviews.

[24]  J. Lafaille,et al.  Interleukin 2 Signaling Is Required for CD4+ Regulatory T Cell Function , 2002, The Journal of experimental medicine.

[25]  J. Trapani,et al.  Suppression of Lymphoma and Epithelial Malignancies Effected by Interferon γ , 2002, The Journal of experimental medicine.

[26]  T. Blankenstein,et al.  Inhibition of Methylcholanthrene-induced Carcinogenesis by an Interferon γ Receptor–dependent Foreign Body Reaction , 2002, The Journal of experimental medicine.

[27]  D. Neuberg,et al.  ATP6S1 elicits potent humoral responses associated with immune-mediated tumor destruction , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[28]  Julia M. Lewis,et al.  Resident Skin-specific γδ T Cells Provide Local, Nonredundant Regulation of Cutaneous Inflammation , 2002, The Journal of experimental medicine.

[29]  K. Kärre NK Cells, MHC Class I Molecules and the Missing Self , 2002, Scandinavian journal of immunology.

[30]  G. Freeman,et al.  The B7–CD28 superfamily , 2002, Nature Reviews Immunology.

[31]  M. Smyth,et al.  Critical Role for Tumor Necrosis Factor–related Apoptosis-inducing Ligand in Immune Surveillance Against Tumor Development , 2002, The Journal of experimental medicine.

[32]  R. Flavell,et al.  Immune-mediated eradication of tumors through the blockade of transforming growth factor-β signaling in T cells , 2001, Nature Medicine.

[33]  C. Thompson,et al.  Induction of Cytotoxic T Lymphocyte Antigen 4 (Ctla-4) Restricts Clonal Expansion of Helper T Cells , 2001, The Journal of experimental medicine.

[34]  Julia M. Lewis,et al.  Regulation of Cutaneous Malignancy by γδ T Cells , 2001, Science.

[35]  T. Schumacher,et al.  Synergism of Cytotoxic T Lymphocyte–Associated Antigen 4 Blockade and Depletion of Cd25+ Regulatory T Cells in Antitumor Therapy Reveals Alternative Pathways for Suppression of Autoreactive Cytotoxic T Lymphocyte Responses , 2001, The Journal of experimental medicine.

[36]  E. Shevach,et al.  Control of T‐cell activation by CD4+ CD25+ suppressor T cells , 2001, Immunological reviews.

[37]  H Nagura,et al.  Proliferative activity of intratumoral CD8(+) T-lymphocytes as a prognostic factor in human renal cell carcinoma: clinicopathologic demonstration of antitumor immunity. , 2001, Cancer research.

[38]  Rolf M. Zinkernagel,et al.  Roles of tumour localization, second signals and cross priming in cytotoxic T-cell induction , 2001, Nature.

[39]  C. Biron Interferons α and β as Immune Regulators—A New Look , 2001 .

[40]  Charles A. Janeway,et al.  INAUGURAL ARTICLE by a Recently Elected Academy Member:How the immune system works to protect the host from infection: A personal view , 2001 .

[41]  Elise C. Kohn,et al.  The microenvironment of the tumour–host interface , 2001, Nature.

[42]  V. Sondak,et al.  High-dose interferon alfa-2b significantly prolongs relapse-free and overall survival compared with the GM2-KLH/QS-21 vaccine in patients with resected stage IIB-III melanoma: results of intergroup trial E1694/S9512/C509801. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[43]  R. Schreiber,et al.  IFNγ and lymphocytes prevent primary tumour development and shape tumour immunogenicity , 2001, Nature.

[44]  J. Egen,et al.  CTLA-4-mediated inhibition in regulation of T cell responses: mechanisms and manipulation in tumor immunotherapy. , 2001, Annual review of immunology.

[45]  Andrew V. Nguyen,et al.  Colony-Stimulating Factor 1 Promotes Progression of Mammary Tumors to Malignancy , 2001, The Journal of experimental medicine.

[46]  K. Uchida,et al.  Intestinal microflora are necessary for development of spontaneous adenocarcinoma of the large intestine in T-cell receptor beta chain and p53 double-knockout mice. , 2001, Cancer research.

[47]  P. Srivastava,et al.  CD91 is a common receptor for heat shock proteins gp96, hsp90, hsp70, and calreticulin. , 2001, Immunity.

[48]  T. Mcclanahan,et al.  Involvement of chemokine receptors in breast cancer metastasis , 2001, Nature.

[49]  E. Jaffee,et al.  The collaboration of both humoral and cellular HER-2/neu-targeted immune responses is required for the complete eradication of HER-2/neu-expressing tumors. , 2001, Cancer research.

[50]  M. Caligiuri,et al.  Fatal Leukemia in Interleukin 15 Transgenic Mice Follows Early Expansions in Natural Killer and Memory Phenotype Cd8+ T Cells , 2001, The Journal of experimental medicine.

[51]  J. Bluestone,et al.  Complexities of CD28/B7: CTLA-4 costimulatory pathways in autoimmunity and transplantation. , 2001, Annual review of immunology.

[52]  L. Grochow,et al.  Novel allogeneic granulocyte-macrophage colony-stimulating factor-secreting tumor vaccine for pancreatic cancer: a phase I trial of safety and immune activation. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[53]  M. Smyth,et al.  Perforin and interferon-gamma activities independently control tumor initiation, growth, and metastasis. , 2001, Blood.

[54]  Jay A. Berzofsky,et al.  NKT cell–mediated repression of tumor immunosurveillance by IL-13 and the IL-4R–STAT6 pathway , 2000, Nature Immunology.

[55]  R. Siegel,et al.  The multifaceted role of Fas signaling in immune cell homeostasis and autoimmunity , 2000, Nature Immunology.

[56]  D. Hanahan,et al.  MMP-9 Supplied by Bone Marrow–Derived Cells Contributes to Skin Carcinogenesis , 2000, Cell.

[57]  G. Dranoff,et al.  Cytokine-secreting tumor cell vaccines. , 2000, Current opinion in immunology.

[58]  K. Seibert,et al.  The cyclooxygenase-2 inhibitor celecoxib is a potent preventive and therapeutic agent in the min mouse model of adenomatous polyposis. , 2000, Cancer research.

[59]  J. Trapani,et al.  Perforin-Mediated Cytotoxicity Is Critical for Surveillance of Spontaneous Lymphoma , 2000, The Journal of experimental medicine.

[60]  H. Adami,et al.  Infections as a major preventable cause of human cancer , 2000, Journal of internal medicine.

[61]  Mark M. Davis,et al.  Evidence that specific T lymphocytes may participate in the elimination of chronic myelogenous leukemia , 2000, Nature Medicine.

[62]  B. Levin,et al.  The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis. , 2000, The New England journal of medicine.

[63]  M. Mihm,et al.  Differences in dendritic cells stimulated in vivo by tumors engineered to secrete granulocyte-macrophage colony-stimulating factor or Flt3-ligand. , 2000, Cancer research.

[64]  S. Soong,et al.  Adjuvant therapy of stage III and IV malignant melanoma using granulocyte-macrophage colony-stimulating factor. , 2000, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[65]  M. Carrington,et al.  Interleukin-1 polymorphisms associated with increased risk of gastric cancer , 2000, Nature.

[66]  J. Trapani,et al.  Differential Tumor Surveillance by Natural Killer (Nk) and Nkt Cells , 2000, The Journal of experimental medicine.

[67]  R. Ren,et al.  Expression of Interferon Consensus Sequence Binding Protein (ICSBP) Is Downregulated in Bcr-Abl-Induced Murine Chronic Myelogenous Leukemia-Like Disease, and Forced Coexpression of ICSBP Inhibits Bcr-Abl-Induced Myeloproliferative Disorder , 2000, Molecular and Cellular Biology.

[68]  D. Hanahan,et al.  The Hallmarks of Cancer , 2000, Cell.

[69]  F. Marincola,et al.  Escape of human solid tumors from T-cell recognition: molecular mechanisms and functional significance. , 2000, Advances in immunology.

[70]  Y. Shima,et al.  Improvement in Castleman's disease by humanized anti-interleukin-6 receptor antibody therapy. , 2000, Blood.

[71]  G. Hannon,et al.  A Proinflammatory Cytokine Inhibits P53 Tumor Suppressor Activity , 1999, The Journal of experimental medicine.

[72]  F. Marshall,et al.  Induction of immunity to prostate cancer antigens: results of a clinical trial of vaccination with irradiated autologous prostate tumor cells engineered to secrete granulocyte-macrophage colony-stimulating factor using ex vivo gene transfer. , 1999, Cancer research.

[73]  J. Sloan,et al.  Aerosol granulocyte macrophage-colony stimulating factor: a low toxicity, lung-specific biological therapy in patients with lung metastases. , 1999, Clinical cancer research : an official journal of the American Association for Cancer Research.

[74]  E. Sotomayor,et al.  A universal granulocyte-macrophage colony-stimulating factor-producing bystander cell line for use in the formulation of autologous tumor cell-based vaccines. , 1999, Human gene therapy.

[75]  J. Allison,et al.  Combination Immunotherapy of B16 Melanoma Using Anti–Cytotoxic T Lymphocyte–Associated Antigen 4 (Ctla-4) and Granulocyte/Macrophage Colony-Stimulating Factor (Gm-Csf)-Producing Vaccines Induces Rejection of Subcutaneous and Metastatic Tumors Accompanied by Autoimmune Depigmentation , 1999, The Journal of experimental medicine.

[76]  G. Kollias,et al.  Mice deficient in tumor necrosis factor-α are resistant to skin carcinogenesis , 1999, Nature Medicine.

[77]  N. Iizuka,et al.  Tumour cells engineered to secrete interleukin-15 augment anti-tumour immune responses in vivo , 1999, British Journal of Cancer.

[78]  C. Rauch,et al.  Tumoricidal activity of tumor necrosis factor–related apoptosis–inducing ligand in vivo , 1999, Nature Medicine.

[79]  R. Mulligan,et al.  Tumor metastasis biopsy as a surrogate marker of response to melanoma immunotherapy. , 1999, Pathology.

[80]  C. Lowenstein,et al.  The Central Role of CD4+ T Cells in the Antitumor Immune Response , 1998, The Journal of experimental medicine.

[81]  D. Neuberg,et al.  Vaccination with irradiated autologous melanoma cells engineered to secrete human granulocyte-macrophage colony-stimulating factor generates potent antitumor immunity in patients with metastatic melanoma. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[82]  Loise M. Francisco,et al.  Immature Dendritic Cells Phagocytose Apoptotic Cells via αvβ5 and CD36, and Cross-present Antigens to Cytotoxic T Lymphocytes , 1998, The Journal of experimental medicine.

[83]  M. Kris,et al.  Quality-of-life benefit in chemotherapy patients treated with epoetin alfa is independent of disease response or tumor type: results from a prospective community oncology study. Procrit Study Group. , 1998, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[84]  H Nagura,et al.  CD8+ T cells infiltrated within cancer cell nests as a prognostic factor in human colorectal cancer. , 1998, Cancer research.

[85]  Piero Musiani,et al.  Interleukin 12–mediated Prevention of Spontaneous Mammary Adenocarcinomas in Two Lines of Her-2/neu Transgenic Mice , 1998, The Journal of experimental medicine.

[86]  F. Chisari,et al.  Immune Pathogenesis of Hepatocellular Carcinoma , 1998, The Journal of experimental medicine.

[87]  R. Schreiber,et al.  Demonstration of an interferon γ-dependent tumor surveillance system in immunocompetent mice , 1998 .

[88]  T. Giese,et al.  Spontaneous Development of Plasmacytoid Tumors in Mice with Defective Fas–Fas Ligand Interactions , 1998, The Journal of experimental medicine.

[89]  Lloyd J. Old,et al.  New Paths in Human Cancer Serology , 1998, The Journal of experimental medicine.

[90]  R. Steinman,et al.  Dendritic cells and the control of immunity , 1998, Nature.

[91]  J. Waring,et al.  Lack of interferon consensus sequence binding protein (ICSBP) transcripts in human myeloid leukemias. , 1998, Blood.

[92]  H. Heimpel,et al.  Interferon alfa versus chemotherapy for chronic myeloid leukemia: a meta-analysis of seven randomized trials: Chronic Myeloid Leukemia Trialists' Collaborative Group. , 1997, Journal of the National Cancer Institute.

[93]  T. Tanimoto,et al.  Interleukin 18 induces the sequential activation of natural killer cells and cytotoxic T lymphocytes to protect syngeneic mice from transplantation with Meth A sarcoma. , 1997, Cancer research.

[94]  P. Musiani,et al.  Defective development of pristane-oil-induced plasmacytomas in interleukin-6-deficient BALB/c mice. , 1997, The American journal of pathology.

[95]  P Signorelli,et al.  Antitumor efficacy of adenocarcinoma cells engineered to produce interleukin 12 (IL-12) or other cytokines compared with exogenous IL-12. , 1997, Journal of the National Cancer Institute.

[96]  T. Blankenstein,et al.  Interleukin-10 prevents dendritic cell accumulation and vaccination with granulocyte-macrophage colony-stimulating factor gene-modified tumor cells. , 1997, Journal of immunology.

[97]  J. Ferlay,et al.  Cancer and infection: estimates of the attributable fraction in 1990. , 1997, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[98]  Robert E. Miller,et al.  Flt3 ligand induces tumor regression and antitumor immune responses in vivo , 1997, Nature Medicine.

[99]  F. Marshall,et al.  Bioactivity of autologous irradiated renal cell carcinoma vaccines generated by ex vivo granulocyte-macrophage colony-stimulating factor gene transfer. , 1997, Cancer research.

[100]  M. Atkins,et al.  Phase I evaluation of intravenous recombinant human interleukin 12 in patients with advanced malignancies. , 1997, Clinical cancer research : an official journal of the American Association for Cancer Research.

[101]  M Aguet,et al.  The IFN gamma receptor: a paradigm for cytokine receptor signaling. , 1997, Annual review of immunology.

[102]  R. Zinkernagel,et al.  Decreased tumor surveillance in perforin-deficient mice , 1996, The Journal of experimental medicine.

[103]  J. Waring,et al.  Immunodeficiency and Chronic Myelogenous Leukemia-like Syndrome in Mice with a Targeted Mutation of the ICSBP Gene , 1996, Cell.

[104]  N. Shastri,et al.  Interleukin 3 enhances cytotoxic T lymphocyte development and class I major histocompatibility complex "re-presentation" of exogenous antigen by tumor-infiltrating antigen-presenting cells. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[105]  Natale Cascinelli,et al.  Prognostic value of tumor infiltrating lymphocytes in the vertical growth phase of primary cutaneous melanoma , 1996, Cancer.

[106]  J. Ritz,et al.  Expansion and manipulation of natural killer cells in patients with metastatic cancer by low-dose continuous infusion and intermittent bolus administration of interleukin 2. , 1996, Clinical cancer research : an official journal of the American Association for Cancer Research.

[107]  P. Bruggen,et al.  Human tumor antigens recognized by T lymphocytes , 1996, The Journal of experimental medicine.

[108]  Y. Tao,et al.  Phase I study of continuous-infusion recombinant macrophage colony-stimulating factor in patients with metastatic melanoma. , 1996, Clinical cancer research : an official journal of the American Association for Cancer Research.

[109]  J. Kirkwood,et al.  Interferon alfa-2b adjuvant therapy of high-risk resected cutaneous melanoma: the Eastern Cooperative Oncology Group Trial EST 1684. , 1996, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[110]  M. Pfreundschuh,et al.  Human neoplasms elicit multiple specific immune responses in the autologous host. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[111]  H. Griesser,et al.  Lymphoproliferative Disorders with Early Lethality in Mice Deficient in Ctla-4 , 1995, Science.

[112]  J. Bluestone,et al.  Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4. , 1995, Immunity.

[113]  S. Rudikoff,et al.  Interleukin 6 is essential for in vivo development of B lineage neoplasms , 1995, The Journal of experimental medicine.

[114]  W C Willett,et al.  The causes and prevention of cancer. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[115]  W. Fair,et al.  Intravesical bacillus Calmette-Guérin therapy prevents tumor progression and death from superficial bladder cancer: ten-year follow-up of a prospective randomized trial. , 1995, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[116]  R. Fisher,et al.  Results of treatment of 255 patients with metastatic renal cell carcinoma who received high-dose recombinant interleukin-2 therapy. , 1995, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[117]  G. Dranoff,et al.  Gene transfer as cancer therapy. , 1995, Advances in immunology.

[118]  J. Folkman Angiogenesis in cancer, vascular, rheumatoid and other disease , 1995, Nature Medicine.

[119]  David Jones,et al.  A personal view , 1994, Nature.

[120]  K. Tracey,et al.  Tumor necrosis factor: a pleiotropic cytokine and therapeutic target. , 1994, Annual review of medicine.

[121]  L. Luistro,et al.  Antitumor and antimetastatic activity of interleukin 12 against murine tumors , 1993, The Journal of experimental medicine.

[122]  S. Steinberg,et al.  Prospective randomized trial of high-dose interleukin-2 alone or in conjunction with lymphokine-activated killer cells for the treatment of patients with advanced cancer. , 1993, Journal of the National Cancer Institute.

[123]  E. Jaffee,et al.  Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[124]  P. Leder,et al.  An eosinophil-dependent mechanism for the antitumor effect of interleukin-4. , 1992, Science.

[125]  A. Burgess,et al.  Granulocyte Colony-Stimulating Factor and Granulocyte-Macrophage Colony-Stimulating Factor , 1992 .

[126]  K. Ozato,et al.  Two upstream elements activate transcription of a major histocompatibility complex class I gene in vitro. , 1992, Nucleic acids research.

[127]  N. Renard,et al.  High-dose recombinant tumor necrosis factor alpha in combination with interferon gamma and melphalan in isolation perfusion of the limbs for melanoma and sarcoma. , 1992, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[128]  T. Blankenstein,et al.  Interleukin 7 induces CD4+ T cell-dependent tumor rejection , 1991, The Journal of experimental medicine.

[129]  D. Pardoll,et al.  Treatment of established renal cancer by tumor cells engineered to secrete interleukin-4. , 1991, Science.

[130]  E. Gilboa,et al.  Interleukin 2 gene transfer into tumor cells abrogates tumorigenicity and induces protective immunity , 1990, The Journal of experimental medicine.

[131]  B. Vogelstein,et al.  Interleukin-2 production by tumor cells bypasses T helper function in the generation of an antitumor response , 1990, Cell.

[132]  A. Halpern,et al.  Model predicting survival in stage I melanoma based on tumor progression. , 1989, Journal of the National Cancer Institute.

[133]  W. Paul Pleiotropy and redundancy: T cell-derived lymphokines in the immune response , 1989, Cell.

[134]  A. Lacic [A new look]. , 1989, Pielegniarka i polozna.

[135]  I. Penn Depressed immunity and the development of cancer. , 1981, Clinical and experimental immunology.

[136]  I. M. Neiman,et al.  [Inflammation and cancer]. , 1974, Patologicheskaia fiziologiia i eksperimental'naia terapiia.