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1.
BACKGROUND: Hemangiosarcoma (HSA) is a highly metastatic and often rapidly fatal tumor of dogs. At present, adjuvant chemotherapy is the only proven effective treatment for dogs with HSA, though the benefits from chemotherapy are modest. Administration of immunotherapy together with chemotherapy has also been reported to improve survival in dogs with HSA. Therefore, we evaluated safety and immunologic responses to a novel tumor vaccine administered together with doxorubicin chemotherapy in dogs with different stages of HSA. HYPOTHESIS: That tumor vaccination could be safely and effectively combined with doxorubicin chemotherapy for treatment of dogs with HSA. ANIMALS: Twenty-eight dogs with various stages of HSA were enrolled in the study. METHODS: The HSA vaccine was prepared with lysates of allogeneic canine HSA cell lines mixed with an adjuvant composed of liposome-DNA complexes. Dogs received a series of 8 immunizations administered over a 22-week period, and most also received chemotherapy. Clinical adverse effects were noted, immune responses were measured by enzyme-linked immunosorbent assay (ELISA) and flow cytometry, and survival times were calculated. RESULTS: The most common adverse effects observed in vaccinated dogs also treated with doxorubicin chemotherapy were diarrhea and anorexia. Vaccinated dogs were found to mount strong humoral immune responses against a control antigen and, most dogs also mounted antibody responses against canine HSA cells. Thirteen dogs with stage II splenic HSA that received the tumor vaccine plus doxorubicin chemotherapy had an overall median survival time of 182 days. CONCLUSIONS: We conclude that an allogeneic tumor lysate vaccine is safe in dogs with HSA and can elicit humoral immune responses in dogs that are receiving concurrent doxorubicin chemotherapy.  相似文献   

2.
Anticancer vaccines.   总被引：1，自引：0，他引：1  
With the tools of molecular biology and a greater understanding of mechanisms to harness the immune system, effective tumor immunotherapy is becoming a reality. This new class of therapeutics offers a more targeted, and therefore precise, approach to the treatment of cancer. The recent conditional licensure of a xenogeneic DNA vaccine for advanced canine malignant melanoma strongly suggests that immunotherapy can play an extremely important role alongside the classic cancer treatment triad components of surgery, radiation therapy, and chemotherapy.  相似文献   

3.
The ability of the immune system to protect against tumor development and to attack malignant cells once they arise has been recognized for more than 50 years. Since this time, our understanding of the complex relation between the immune system and the development of cancer has increased dramatically, largely because of improvements in the tools used to study tumor immunology at the molecular level. These advances are leading to the development of increasingly sophisticated and effective immunotherapeutics for human and veterinary oncology patients; indeed, some forms of immunotherapy already have a place alongside more conventional treatment modalities, such as surgery, radiation therapy, and chemotherapy.  相似文献   

4.
Melanoma is a common neoplastic disease of dogs with variable presentation and biological behavior. Canine malignant melanoma is a rapidly metastatic disease that generally is incurable. The loss of function of cellular safeguards built into the genetic program and of immune surveillance systems that cooperate to prevent tumor formation and progression appear to be important underlying causes of canine malignant melanoma. In effect, many existing cancer treatments restore the function of 1 or the other of these mechanisms. For example, chemotherapy and radiotherapy often kill tumor cells by initiating a genetic suicide mechanism (apoptosis), and immunotherapy initiates or enhances a response by the body's immune cells to identify and destroy cancer cells by mechanisms that rely on direct cytotoxicity or apoptotic cell death. Nevertheless, standard therapeutic approaches have not proved effective in treatment of canine malignant melanoma, with only marginal improvement in the outcome of dogs with this disease. The advantages of an improved understanding of the molecular basis of canine cancer are underscored by recent promising advances in diagnosis and in immunologic and genetic therapies that may help reduce the mortality of dogs affected with malignant melanoma.  相似文献   

5.
We report a case of ovarian malignant intermediate-type trophoblastic tumor in a clinically normal, nonpregnant 4-year-old rhesus monkey (Macaca mulatta). A large solid lobulated mass replaced the right ovary and filled the pelvis. Multiple metastases were observed within the lungs and the liver. The tumor was histologically identified as predominantly composed of intermediate trophoblastic cells, without prominent hemorrhages and the classic bilaminar pattern of cyto- and syncytiotrophoblastic cells characteristic of choriocarcinoma. Immunohistochemical analysis showed the presence of placental lactogen hormone in many tumor cells and chorionic gonadotropin in a few multinucleated cells consistent with syncytiotrophoblastic differentiation. No other germ cell differentiation was identified in the pelvis mass nor in the metastases. In the absence of previous and present pregnancy, this neoplasm has to be considered as a nongestational malignant placental site trophoblastic tumor of the ovary.  相似文献   

6.
Five dogs with ostoegenic sarcoma were treated by surgical removal of the primary tumor and by adjuvant chemotherapy. Methotrexate at dosages of 3 to 6 g/m2 was used with leucovorin rescue. All dogs tolerated E g of methotrexate/m2 of body surface, but granulocytopenia precluded escalation beyond this dosage in 4 dogs. The rate and time of appearance of pulmonary metastases were not altered by treatment, with all dogs developing metastases at a median time of 4 months after amputation.  相似文献   

7.
A three-year-old male crossbred dog was presented with multiple cutaneous nodules on the dorsum. Unilateral testicular enlargement ensued. Histopathological examination of testicular tissue and the skin lesions revealed a malignant seminoma. Despite the initiation of adjuvant chemotherapy, the dog died three months later due to systemic metastases of the seminoma to the skin, scrotum, eyes, liver, kidney and peritoneum.  相似文献   

8.
Canine malignant melanoma (CMM) is a common and aggressive form of cancer in dogs. Established therapeutic approaches such as surgery, chemotherapy, and radiation therapy (RT) have not proven curative. As a coadjuvant of RT and to enhance the antimelanoma immune response, we characterized dendritic cells (DCs) from the bone marrow (BM) of dogs with CMM, ex vivo, for use in therapeutic vaccines. BM mononuclear cells from 3 dogs with melanoma and from 1 healthy dog were cultured for 12 days in media supplemented with recombinant human granulocyte-macrophage colony stimulating factor, stem cell factor, tumor necrosis factor, and Flt-3 ligand. On day 11, DCs were transduced with an adenovirus vector encoding a xenoantigen, human melanoma antigen gp100. Each dog received 3 subcutaneous vaccinations over a 4-month period. Phenotypic analysis of the expanded DC population demonstrated expression of CD11c/CD18 and major histocompatibility complex class II surface markers, and ultrastructural features characteristic of DCs were observed on electron microscopy. On functional analysis, these DCs were able to stimulate allo-reactivity and capture and express gp100. One dog demonstrated antigen-specific cytotoxic T lymphocyte (CTL) activity in peripheral blood lymphocytes. This dog has displayed no clinical signs, either locally or systemically, of recurrent melanoma 48 months after initial DC injection. However, another dog, which was CTL negative, relapsed 22 months after vaccination. Ex vivo DC expansion is feasible for immunotherapy of spontaneous cancers in outbred dogs.  相似文献   

9.
These last years, significant progress has been made in the design of strategies empowering T cells with efficient anti-tumor activities. Hence, adoptive T cell therapy and the use of monoclonal antibodies against the immunosuppressive surface molecules CTLA-4 and PD-1 appear as the most promising immunotherapies against cancer. One of the challenges ahead is to render these therapeutic interventions even more effective as a still elevated fraction of cancer patients is refractory to these treatments. A frequently overlooked determinant of the success of T cell-based immunotherapy relates to the ability of effector T cells to migrate into and within tumors, as well as to have access to tumor antigens. Here, we will focus on recent advances in understanding T cell trafficking into and within tumors. Both chemoattractant molecules and structural determinants are essential for regulating T cell motile behavior along with cellular interactions-mediated antigen recognition. In addition, we will review evidence that the microenvironment of advanced tumors creates multiple obstacles limiting T cells from migrating and making contact with their malignant targets. We will particularly focus on the extracellular matrix and tumor-associated macrophages that make tumors a hostile environment for T cell ability to contact and kill malignant cells. Finally, we will discuss possible strategies to restore a tumor microenvironment more favorable to T cell migration and functions with a special emphasis on approaches targeting the dysregulated extracellular matrix of growing tumors.  相似文献   

10.
Canine mammary tumours are generally treated with surgery alone, despite the fact that 50% of them are malignant and many will eventually lead to recurrence or metastases. A prospective clinical trial in which dogs with aggressive mammary carcinoma of clinical stages IV and V were treated with surgical excision (n = 9) or with surgery and adjuvant weekly gemcitabine (n = 10) for at least four cycles was conducted. Gemcitabine was given as an intravenous infusion at the dose of 800 mg m?2. Aim of the study was to explore potential beneficial effects of gemcitabine on time to local recurrence (TTR), time to distant metastases (TTM) and overall survival (OS) in canine patients with operated mammary tumours bearing high risk for locoregional failure and distant metastases. Also, factors associated with OS, including neutering status, body weight, age, clinical stage at presentation, tumour size, histological grade and, in dogs receiving chemotherapy, the number of gemcitabine treatments, were investigated. Finally, acute toxicities related to chemotherapy and quality of life were assessed in dogs receiving gemcitabine. Dogs treated with surgery alone or surgery followed by gemcitabine had no difference in TTR, TTM or OS (P > 0.05). In the group of dogs receiving adjuvant chemotherapy, the number of gemcitabine treatments was positively correlated with OS (P = 0.017). Gemcitabine treatment was well tolerated, with no dogs experiencing clinically relevant haematological or gastrointestinal toxicity. Despite being safe at the present dose, gemcitabine chemotherapy as an adjunct treatment to surgical excision may not be recommended in dogs with aggressive mammary carcinoma.  相似文献   

11.
Even after using the first arms against tumour (surgery and radiotherapy) 70% of solid tumours reappear. Chemotherapy cannot eliminate ‘the last cell’. Specific and/or non specific immunotherapy helps the organism to eliminate the last cells by stimulating its immune capacity.

The different generations of adjuvants, agents of immunotherapy were studied successively. BCG belongs to the first generation of adjuvants. We considered its association with specific immunotherapy (of irradiated tumour cells) and/or chemotherapy (cyclophosphamide), then we analysed the problems of dose and the ways of administration, advantages and disadvantages (stimulation of suppressor cells).

Second generation of adjuvant (Corynebacterium parvum, nucleotids and levamisole) allowed to specify the parameters of the efficiency of adjuvants. They have the same disadvantages as BCG.

Finally the third generation share the following characteristics: their side-effects will be minimal (they will not induce suppressor cells), their action will be limited to stimulate one population of cells only and they will be well defined chemical compounds. Thymosin, Bestatin and MDP belong to this generation. Combinations of adjuvants may also be envisaged with the objective of stimulating a particular mechanism of antitumoural activity.  相似文献   


12.
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13.
Osteosarcoma is a malignant mesenchymal neoplasm that accounts for the majority of primary bone tumors in dogs and shares biological and clinical similarities with osteosarcoma in humans. Despite dose intensification with conventional cytotoxic therapies, survival times for dogs and humans diagnosed with high‐grade osteosarcoma have not changed in the past 20 years, with the principal cause of mortality being the development of pulmonary metastases. Given the therapeutic plateau reached for delaying metastatic progression with cytotoxic agents, exploration of alterative adjuvant therapies for improving management of osteosarcoma micrometastases is clinically justified. Evidence suggests that osteosarcoma is an immunogenic tumor, and development of immunotherapies for the treatment of microscopic lung metastases might improve long‐term outcomes. In this review, the history and foundational knowledge of immune interactions to canine osteosarcoma are highlighted. In parallel, immunotherapeutic strategies that have been explored for the treatment of canine osteosarcoma are summarized. With a greater understanding and awareness for how the immune system might be redirected toward combating osteosarcoma metastases, the rational development of diverse immune strategies for managing osteosarcoma holds substantial promise for transforming the therapeutic landscape and improving disease management in both dogs and human beings.  相似文献   

14.
Orbital epithelial tumors in dogs are rare and most frequently malignant. Distinguishing their origin from the lacrimal or zygomatic gland is often challenging and is based mostly on tumor location. A case of adenoma involving the orbit in a 13-year-old, female, standard Schnauzer is reported. Histologically, the neoplasm was characterized by nests and cords of epithelial cells mostly forming small glandular structures. The origin of the tumor from the zygomatic gland was determined by histochemical characteristics (alcian blue pH 1 positive staining) of a small remnant of normal gland included within the tumor capsule. The benign nature of our finding was confirmed by follow-up information: 2 years after complete surgical removal of the mass no tumor recurrence or metastases was recorded.  相似文献   

15.
The safety and efficacy of intra‐incisional 5‐fluorouracil (5‐FU) in the management of incompletely resected malignant spindle cell tumours of extremities was evaluated in six dogs. After marginal surgery, the dogs underwent weekly intra‐incisional 5‐FU for a minimum of six cycles. Treatment was well tolerated by all dogs, with no systemic adverse effects and only one episode of local cutaneous hyperpigmentation, which completely and spontaneously resolved. Median follow‐up for all the dogs was 546 days (mean 619; range 297–1207). At the date of analysis, four dogs were still alive with no evidence of local recurrence, and two dogs had died as a result of their disease. The cause of death was development of distant metastases in one dog and tumour regrowth in the other. Despite the small sample size, this study documents that intra‐incisional 5‐FU chemotherapy is a safe and efficacious adjuvant treatment in the case of incompletely resected malignant spindle cell tumours in dogs and that long disease control can be achieved.  相似文献   

16.
端粒是一段存在于真核细胞染色体末端,随着细胞分裂而缩短的特殊结构。端粒酶可延长端粒,但在正常人体细胞内活性较低或无活性。大多数肿瘤细胞通过激活端粒酶活性,延伸端粒达到细胞无限增殖的可能。端粒酶的活性与肿瘤的发生密切相关。本文以近年来临床常见的恶性肿瘤为出发点,综述了其与端粒酶活性关系及端粒酶抑制剂的最新研究。  相似文献   

17.
Three dogs with advanced-stage adenocarcinoma of the gastrointestinal tract were treated by use of resection, adjuvant chemotherapy with cisplatin and 5-fluorouracil, and second-look laparotomy (SLL). In combination with histologic examination of biopsy specimens obtained during the procedure, SLL is the most accurate diagnostic procedure for identification of residual or recurrent microscopic or macroscopic abdominal neoplasia; however, to the authors' knowledge, there are no reports of its clinical use in the field of veterinary oncology. This lack of clinical use in animals is likely because of factors such as cost, procedure-associated risks perceived by the owners and veterinarians, lack of data to define proper clinical application, and, perhaps to some degree, an entrenched belief that treatment of advanced stage cancer in animals is inappropriate. Nevertheless, the use of SLL should be considered for evaluation of abdominal tumors or intra-abdominal metastases in dogs that appear to be in complete clinical remission near or at the anticipated completion of chemotherapy (especially if effective second-line chemotherapy protocols are available) or when secondary cytoreduction might be beneficial.  相似文献   

18.
CD47属于免疫球蛋白家族成员之一,广泛存在于细胞膜表面,特别是在肿瘤细胞中高表达。肿瘤细胞表面的CD47可与巨噬细胞表面的抑制性免疫受体--信号调节蛋白α(SIRPα)相结合,形成CD47-SIRPα信号复合体,该复合体能抑制巨噬细胞对肿瘤细胞的吞噬,使肿瘤细胞逃避免疫监视,从而促进肿瘤的发展。目前免疫治疗主要是通过抗CD47抗体抑制CD47-SIRPα信号通路,激活先天性免疫反应和适应性免疫反应,提高巨噬细胞靶向杀伤肿瘤细胞的能力。CD47-SIRPα正逐渐成为肿瘤免疫治疗的新型有效免疫治疗靶标,论文对CD47-SIRPα阻断剂在实体癌和血液癌的研究现进行以综述,以期为实体癌和血液癌的研究提供参考。  相似文献   

19.
The National Consensus Group recommends that all women with tumors larger than 1 cm be offered chemotherapy regardless of tumor histology of lymph node status. This recommendation is to ensure that everyone at risk for failing, even though the risk may be low in women with relatively small tumors and favorable histology, has a choice and receives the benefit of adjuvant chemotherapy. This type of treatment recommendation may also be made in dogs based on recognized, well-accepted prognostic factors such as tumor size, stage, type, and histologic differentiation. Based on the limited clinical information available in veterinary medicine, the drugs that are effective in human breast cancer, such as cyclophosphamide, 5-fluorouracil, and doxorubicin, may also have a role in the treatment of malignant mammary gland tumors in dogs. Randomized prospective studies are needed, however, to evaluate the efficacy of chemotherapy in dogs with high-risk mammary gland tumors and to determine which drugs and protocols are the most efficacious. Until such studies are performed, the treatment of canine mammary gland tumors will be based on the individual oncologist's understanding of tumor biology, experience, interpretation of the available studies, and a little bit of gut-feeling. Table 2 is a proposal for treatment guidelines for malignant canine mammary gland tumors according to established prognostic factors, results from published veterinary studies, and current recommendations for breast cancer treatment in women.  相似文献   

20.
Thirty-six dogs underwent pulmonary metastatectomy for osteosarcoma. All patients had been treated for histologically confirmed osteosarcoma of the appendicular skeleton. Treatment for the primary tumor consisted of amputation or a limb sparing procedure in conjunction with adjuvant chemotherapy, local radiation therapy, or both.
Significant factors in determining prognosis included the disease-free interval (DFI) between treatment of the primary tumor and development of pulmonary metastases and the number of metastatic nodules present at surgery. Dogs that developed pulmonary metastases 300 days or more after diagnosis of the primary tumor had a median DFI of 128 days after metastatectomy. Dogs that developed pulmonary metastases fewer than 300 days after diagnosis had a median DFI of 58 days. Dogs with one or two metastatic nodules removed had a median DFI of 95 days, whereas dogs with three or more nodules removed had a median DFI of 53 days. The results of this study indicate that prognostic variables exist for dogs with metastatic pulmonary osteosarcoma and can help predict survival after metastatectomy. These variables are similar to the prognostic variables that have been determined for human patients undergoing pulmonary metastatectomy because of osteosarcoma. Though a controversial procedure, pulmonary metastatectomy seems to be a valid treatment option for selected dogs with metastatic pulmonary osteosarcoma.  相似文献   

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