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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Proposing that a blend of the chemical diversity of small synthetic molecules with the immunological characteristics of the antibody molecule will lead to therapeutic agents with superior properties, we here present a device that equips small synthetic molecules with both effector function and long serum half-life of a generic antibody molecule. As a prototype, we developed a targeting device that is based on the formation of a covalent bond of defined stoichiometry between a 1,3-diketone derivative of an integrin alpha(v)beta(3) and alpha(v)beta(5) targeting Arg-Gly-Asp peptidomimetic and the reactive lysine of aldolase antibody 38C2. The resulting complex was shown to (i) spontaneously assemble in vitro and in vivo, (ii) selectively retarget antibody 38C2 to the surface of cells expressing integrins alpha(v)beta(3) and alpha(v)beta(5), (iii) dramatically increase the circulatory half-life of the Arg-Gly-Asp peptidomimetic, and (iv) effectively reduce tumor growth in animal models of human Kaposi's sarcoma and colon cancer. This immunotherapeutic has the potential to target a variety of human cancers, acting on both the vasculature that supports tumor growth as well as the tumor cells themselves. Further, by use of a generic antibody molecule that forms a covalent bond with a 1,3-diketone functionality, essentially any compound can be turned into an immunotherapeutic agent thereby not only increasing the diversity space that can be accessed but also multiplying the therapeutic effect.
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PMID:Chemically programmed monoclonal antibodies for cancer therapy: adaptor immunotherapy based on a covalent antibody catalyst. 1270 56

Paclitaxel is one of the best antineoplastic drugs found from nature in the past decades, which has been found effective against a wide spectrum of cancers including ovarian cancer, breast cancer, small and non small cell lung cancer, colon cancer, head and neck cancer, multiple myeloma, melanoma, and Kaposi's sarcoma. Like many other anticancer drugs, it has difficulties in clinical administration due to its poor solubility in water and most pharmaceutical reagents. In its current clinical application, an adjuvant called Cremophor EL has to be employed, which has been found to be responsible for many serious side effects. Nanoparticles of biodegradable polymers can provide an ideal solution to such an adjuvant problem and realize a controlled and targeted delivery of the drug with better efficacy and less side effects. With further development, such as particle size optimization and surface coating, nanoparticle formulation of paclitaxel can promote a new concept of chemotherapy to realize its full efficacy and to improve quality of life of the patients, which includes personalized chemotherapy, local chemotherapy, sustained chemotherapy, oral chemotherapy, chemotherapy across the blood-brain barrier, chemotherapy across the microcirculation barrier, etc. The present research proposes a novel formulation for fabrication of nanoparticles of poly(lactic-co-glycolic acid) (PLGA) by a modified solvent extraction/evaporation technique, in which natural emulsifiers, such as phospholipids, cholesterol and vitamin E TPGS are creatively applied to achieve high drug encapsulation efficiency, desired drug released kinetics, high cell uptake and high cytotoxicity. The nanoparticles composed of various recipes and manufactured under various conditions were characterized by laser light scattering (LLS) for size and size distribution, scanning electron microscopy (SEM) and atomic force microscopy (AFM) for morphological properties, X-ray photoelectron spectroscopy (XPS) and Fourier Transformation Infrared Spectroscopy (FTIR) for surface chemistry, zeta-potential for surface charge, and differential scanning calorimetry (DSC) for the thermogram properties. The drug encapsulation efficiency and the drug release kinetics under in vitro conditions were measured by high performance liquid chromatography (HPLC). It was found that these natural emulsifiers have great advantages for nanoparticle formulation of paclitaxel over the traditional macromolecular emulsifiers, such as polyvinyl alcohol (PVA). Nanoparticles of desired small size and narrow size distribution can be obtained. The drug encapsulation efficiency can be achieved as high as 100 %. The released kinetics can be made under control. The HT-29 cancer cell line experiment showed that after 24 hours of incubation, the cell mortality caused by the drug administered by such nanoparticle formulation could be more than 13 times higher than that caused by the free drug under similar conditions.
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PMID:Nanoparticles of biodegradable polymers for clinical administration of paclitaxel. 1496 22

The objective of this study was to analyse incidence and mortality cancer trends in the Italian Network of Cancer Registries (about 8,000,000 inhabitants) during the period 1986-1997. Included were 525,645 newly diagnosed cancers and 269,902 cancer deaths (subjects > 14 years). Joinpoints (points in time where trend significantly changes from linearity) were found and estimated annual percentage changes (EAPC) used to summarize tendencies. Overall cancer incidence increased in both sexes and cancer mortality significantly decreased (since 1991 among men). Lung cancer showed significantly decreasing incidence (EAPC = -1.4%) and mortality (EAPC = -1.6%) among men and increasing trends among women. In women, breast cancer incidence significantly increased (EAPC= +1.7%) and mortality decreased since 1989 (EAPC= -2.0%). Stomach cancer incidence and mortality decreased in both sexes. Prostate incidence sharply increased since 1991 and mortality decreased. Colon cancer incidence increased and rectum mortality decreased significantly in both sexes. Significant increases in incidence were also found for kidney (up to 1991 among men), urinary bladder, skin epithelioma, melanoma, liver (up to 1993 among men), pancreas, mesothelioma, Kaposi's sarcoma (up to 1995 among men), testis, thyroid, non-Hodgkin's lymphomas and multiple myeloma. Mortality significantly decreased for cancers of the oral cavity and pharynx, oesophagus, liver (women), larynx (men), bone, cervix (since 1990), central nervous system, urinary bladder, thyroid, Hodgkin's lymphomas and leukaemias (men). Non-Hodgkin's lymphoma mortality increased in both sexes. In conclusion, most of the changes seen can be explained as the effect of changes in smoking habits and of the extension of secondary prevention activities. The Italian health care system will also have to cope with growing cancer diagnostic and therapeutic needs due to population ageing.
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PMID:Population-based incidence and mortality cancer trends (1986-1997) from the network of Italian cancer registries. 1555 57

ILEX Oncology is developing the dihydrofolate reductase inhibitor, piritrexim (discovered originally by Burroughs Wellcome), for the potential treatment of cancer. It is in phase II clinical trials for malignant fibrous histiocytoma. ILEX conducted phase II clinical trials in the US and Europe with piritrexim in bladder cancer patients; however, development for this indication was discontinued in the third quarter of 1998 due to lack of efficacy. The company also initiated phase III trials in early 1997 for the treatment of AIDS-related Kaposi's sarcoma, but no further development for this indication has been reported since that time. Piritrexim was discovered by Burroughs Wellcome, which conducted phase I and II clinical trials in more than 700 patients. Due to its potentially superior properties to those of methotrexate, it was expected that piritrexim would be active in certain methotrexate-resistant tumors. Tumor responses were noted in patients with advanced bladder cancer, Kaposi's sarcoma, colon cancer, melanoma, head and neck cancer and other cancer types. In published phase II studies, piritrexim demonstrated objective response rates ranging from 23 to 75% in patients with advanced bladder cancer who failed a standard first-line chemotherapy regimen. In March 1995, ILEX acquired an exclusive, worldwide license to patents held by Burroughs Wellcome covering the composition and use of piritrexim for all cancer indications. Under the terms of the agreement, ILEX paid a licensing fee and is obligated to pay Wellcome royalties on net sales of piritrexim. In December 1996, ILEX formed a joint venture with MPI Enterprises for the manufacture and marketing of piritrexim.
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PMID:Piritrexim (ILEX Oncology). 1611 90

During the last 2 decades, long-term survival after lung transplantation has significantly improved. However, among the complications related to the continuous administration of immunosuppressive drugs, malignancy plays an important role. We retrospectively revisited our series of patients to report our experience. From January 1991 we performed 134 lung transplantations in 128 recipients (mean age, 33.4 +/- 13.5 years). In all patients the first-line immunosuppressive regimen was based on a calcineurin inhibitor (cyclosporine or tacrolimus), an antimetabolic agent (azathioprine), and steroids. Five patients (4.2%) developed malignancy and the mean time of occurrence after the transplantation was 46.4+/-23 months. The mean age was 41 +/- 16 years (P = not significant [ns]). The tumors were as follows: laryngeal cancer (radiotherapy), colon cancer (surgery plus adjuvant chemotherapy), gastric cancer (surgery plus adjuvant chemotherapy), endobronchial non-Hodgkin lymphoma (NHL) (endoscopic resection plus chemoradiotherapy), and cutaneous and visceral Kaposi's sarcoma (KS) (chemotherapy). All patients have reduced the dose of immunosuppressive drugs; in 1 of them, tacrolimus was changed to rapamycin. Two patients died because of neoplastic dissemination, another 1 due to obliterans bronchiolitis. The 2 patients with NHL and KS are alive at 6 and 9 months, respectively, without signs of recurrence. Malignancies after lung transplantation represent an important problem. A multidisciplinary approach is mandatory to obtain satisfactory results in terms of improved quality of life and long-term survival.
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PMID:Malignancies following lung transplantation. 1769 72

The occurrence of malignancies is a well-known serious complication after organ transplantation. Despite the fact that many factors may be involved, the pathogenesis is still unclear. The aim of the present study was to examine the incidence and clinical characteristics of de novo malignancies that arise after renal transplantation over a 13-year experience in a single center in the Balkan Peninsula. During this period, 185 renal transplantations (139 living related and 46 cadaveric) were followed in our department. Overall, 19 malignancies (9.78%) were observed in 15 patients (7.8%). The mean age of these patients was 45 years (range, 21-53 years). Ten patients (55%) developed skin cancers: 8 squamous and 2 basal cell. Kaposi's sarcomas were found in 3 patients (16.6%, 1 visceral form). We also detected 1 breast cancer, 1 seminoma, 1 colon cancer, 1 urogenital-transitional cell-like cancer, 1 renal cell carcinoma, 1 plasmacytoma, and 1 retroperitoneal sarcoma after an ABO incompatible transplantation. All cancers were de novo malignancies that presented at a mean time of 21 months (range, 2-52 months) after surgery. In conclusion, the incidence of malignancy in the present series was similar to that reported elsewhere. The predominance of skin cancers was understandable bearing in mind the sunshine. The appearance of skin malignancies in our group of patients was earlier, more severe, and multiple sites. No cases of posttransplantation lymphoproliferative disorders were observed. Careful clinical examination and long-term screening protocols are needed for early detection and treatment of this life-threatening complication among the transplant population.
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PMID:De novo malignancies after renal transplantation--a single-center experience in the Balkans. 1795 84

Kaposi's sarcoma (KS) is a multicentric, malignant neoplasm of a complex and still unclear etiology. We present the case of 87-year-old man referred to our dermatology department with the coexistence of two separate malignances: nodular KS and colon cancer. The patient observed the cutaneous nodules 3 months after colon cancer surgery. The question arises of whether the intestinal malignancy-associated weakened immune system exacerbated what was potentially preexisting but unapparent KS, or actually triggered development of KS.
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PMID:Nodular Kaposi's sarcoma associated with colon cancer. 2199 7

The role of cyclooxygenase-2 (COX-2), its lipid metabolite prostaglandin E2 (PGE2), and Eicosanoid (EP) receptors (EP; 1-4) underlying the proinflammatory mechanistic aspects of Burkitt's lymphoma, nasopharyngeal carcinoma, cervical cancer, prostate cancer, colon cancer, and Kaposi's sarcoma (KS) is an active area of investigation. The tumorigenic potential of COX-2 and PGE2 through EP receptors forms the mechanistic context underlying the chemotherapeutic potential of nonsteroidal anti-inflammatory drugs (NSAIDs). Although role of the COX-2 is described in several viral associated malignancies, the biological significance of the COX-2/PGE2/EP receptor inflammatory axis is extensively studied only in Kaposi's sarcoma-associated herpes virus (KSHV/HHV-8) associated malignancies such as KS, a multifocal endothelial cell tumor and primary effusion lymphoma (PEL), a B cell-proliferative disorder. The purpose of this review is to summarize the salient findings delineating the molecular mechanisms downstream of COX-2 involving PGE2 secretion and its autocrine and paracrine interactions with EP receptors (EP1-4), COX-2/PGE2/EP receptor signaling regulating KSHV pathogenesis and latency. KSHV infection induces COX-2, PGE2 secretion, and EP receptor activation. The resulting signal cascades modulate the expression of KSHV latency genes (latency associated nuclear antigen-1 [LANA-1] and viral-Fas (TNFRSF6)-associated via death domain like interferon converting enzyme-like- inhibitory protein [vFLIP]). vFLIP was also shown to be crucial for the maintenance of COX-2 activation. The mutually interdependent interactions between viral proteins (LANA-1/vFLIP) and COX-2/PGE2/EP receptors was shown to play key roles in the biological mechanisms involved in KS and PEL pathogenesis such as blockage of apoptosis, cell cycle regulation, transformation, proliferation, angiogenesis, adhesion, invasion, and immune-suppression. Understanding the COX-2/PGE2/EP axis is very important to develop new safer and specific therapeutic modalities for KS and PEL. In addition to COX-2 being a therapeutic target, EP receptors represent ideal targets for pharmacologic agents as PGE2 analogues and their blockers/antagonists possess antineoplastic activity, without the reported gastrointestinal and cardiovascular toxicity observed with few a NSAIDs.
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PMID:Cyclooxygenase-2-prostaglandin E2-eicosanoid receptor inflammatory axis: a key player in Kaposi's sarcoma-associated herpes virus associated malignancies. 2356 32

Primary vascular tumors of the lymph nodes other than Kaposi's sarcoma are rare. The present study describes the case of a primary hemangioendothelioma in a cervical lymph node in a patient treated for a carcinoma of the large bowel. Microscopically, the structure of the lymph node was completely substituted by tumoral proliferation, with an architectural pattern consisting of anastomosing vascular channels, a number of which contained papillary projections or a tuft-like structure. This study demonstrates the potential diagnostic errors and hypothesizes the pathogenesis of this type of lesion; a vascular endothelial growth factor (VEGF)/VEGF receptor-3 (VEGFR-3) autocrine loop may be activated.
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PMID:A rare case of primary nodal hemangioendothelioma. 2426 72

Ameboma is a rare complication of amebic colitis presenting as a mass of granulation tissue with peripheral fibrosis and a core of inflammation related to amebic chronic infection. The initial presentations are usually obstruction and low gastrointestinal bleeding. The most common sites are the ascending colon and the cecum. It may mimic colon carcinoma, Crohn's disease, carcinoma of the colon, non-Hodgkin's lymphoma, tuberculosis, fungal infection, AIDS-associated lymphoma and Kaposi's sarcoma in colonoscopy findings. The therapeutic strategy should be combined with antibiotics for invasive dysentery and eradication of luminal cysts.
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PMID:Ameboma: a colon carcinoma-like lesion in a colonoscopy finding. 2440 82


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