Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038002 (splenomegaly)
 9,873 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The development of therapeutic anti-cancer vaccines designed to elicit CTL responses with anti-tumor activity has become a reality thanks to the identification of several tumor-associated Ags and their corresponding peptide T cell epitopes. However, peptide-based vaccines, in general, fail to elicit sufficiently strong CTL responses capable of producing therapeutic anti-tumor effects (i.e., prolongation of survival, tumor reduction). Here we report that repeated administration of synthetic oligonucleotides containing foreign cytosine-phosphorothiolated guanine (CpG) motifs increased 10- to 100-fold the CTL response to immunization with various synthetic peptides corresponding to well-known T cell epitopes. Moreover, repeated CpG administration allowed the induction of CTL to soluble protein even in the absence of additional adjuvant. Our results indicate that the potentiating effect of CpG in CTL responses required the participation of Th lymphocytes. Repeated CpG administration resulted in overt splenomegaly and lymphadenopathy with a significant increase in the numbers of CTL precursors and dendritic cells. Protein vaccination in combination with repeated CpG therapy was effective in delaying tumor cell growth and extending survival in mice bearing melanoma tumors. These findings support the contention that repeated administration of CpG-oligonucleotides enhances the effect of peptide and protein vaccines leading to potent anti-tumor responses, presumably through the induction of Th1 and dendritic cells, which are essential for optimal CTL responses. The immunostimulatory properties of CpG motifs may be key in inducing a consistent long term immunity to tumor-associated Ags when using peptides or proteins as T cell-inducing vaccines.
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PMID:Repeated administration of cytosine-phosphorothiolated guanine-containing oligonucleotides together with peptide/protein immunization results in enhanced CTL responses with anti-tumor activity. 1086 Oct 94

A thirty-five year old woman presented with bilateral neck, chest wall and back masses. She was 16 weeks pregnant. Lymph node excision revealed metastatic poorly differentiated adenocarcinoma of unknown primary. Abdominal ultrasound showed a mildly enlarged spleen and a 2-3 cm porta hepatis node. All other investigations were negative. The lymph node and cutaneous metastases progressed rapidly so it was decided to initiate systemic chemotherapy with a view to delivery at 28 weeks gestation by Caesarean section. Shortly after the second 3-weekly cycle of cisplatinum chemotherapy the patient suffered severe lower back and hip pain with MRI scan showing multiple bony metastases in the pelvic girdle. Ultrasound revealed the fetus to have been dead for at least 10 days. The products of conception were delivered following medical induction of labour. Two days later the patient suffered a cardiac arrest from which she could not be resuscitated. Placental histology revealed extensive metastases. With the exception of melanoma this has rarely been reported in solid adult malignancy. As a cause of fetal death, placental metastases are extremely rare.
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PMID:Intra-uterine death resulting from placental metastases in adenocarcinoma of unknown primary. 1210 24

The Bcl-2 antisense oligonucleotide (AS-ODN) G3139 chemosensitizes human malignancies by downregulating the antiapoptotic protein Bcl-2. Because G3139 contains two potential immunostimulatory CpG motifs, we asked if immune stimulation contributes to the antitumor activity observed previously. 5'-Methylation of cytosines in CpG motifs abrogates immune stimulation by oligonucleotides. We, therefore, studied the antitumor and immunostimulatory potential of G3139 vs. an identical oligonucleotide, except for methylation of cytosines in the two CpG motifs (G4232). In a human melanoma SCID mouse xenotransplantation model, G3139 or G4232 was administered by continuous subcutaneous (s.c.) or bolus intraperitoneal (i.p.) infusion. Both G3139 and G4232 significantly reduced tumor growth by about one third relative to the saline-treated group. Furthermore, we noted a similar downregulation of Bcl-2 expression and increase in tumor cell apoptosis caused by G3139 and G4232 compared with saline controls. However, mice treated with G3139 had a pronounced increase in spleen weight and interleukin-12 (IL-12) plasma levels relative to mice treated with either G4232 or saline. Splenomegaly and elevated IL-12 plasma levels suggest that G3139 can be immunostimulatory. However, there is clear evidence that the antitumor effect of G3139 in this model appears to be a Bcl-2 antisense effect that is independent of immune stimulation, as G3139 and its immune-silent counterpart G4232 caused similar tumor suppression and apoptosis induction.
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PMID:Antitumor effect of G3139 Bcl-2 antisense oligonucleotide is independent of its immune stimulation by CpG motifs in SCID mice. 1256 10

Metastatic disease involving the spleen is uncommon, and isolated metastasis to the spleen is extremely rare. Most patients with splenic metastases have widely disseminated metastatic disease. A current literature review shows the incidence of isolated splenic metastasis ranges from 0 to 26% of all patients with splenic metastases. The reported primary malignancies of patients with splenic metastases include lung, colorectal, endometrial, ovarian, thyroid, pancreatic, gastric cancers, and, most commonly, melanoma. Although most patients with splenic metastases are clinically asymptomatic for splenic lesions, there have been reports of painful splenomegaly, splenic vein thrombosis, and splenic rupture, making diagnosis and consideration of prompt therapeutic intervention important. The time from diagnosis of a primary lung tumor to the discovery of splenic metastases ranges from 0 to 8 years in the literature. We report a rare case of an asymptomatic, isolated splenic metastasis in a 72-year-old man diagnosed 25 months after resection of an adenocarcinoma of the lung.
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PMID:Isolated splenic metastasis from primary lung adenocarcinoma. 1504 41

A 63-year-old woman presented to the internist with fatigue, cough, low-grade fever, splenomegaly and leucocytosis up to 130 x 10(9)/l. Although a diagnosis of chronic myelogenous leukaemia was initially entertained, she turned out to have a metastasised melanoma. The differential diagnosis and workup is discussed, as well as potential mechanisms by which the tumour could have induced the leucocytosis, such as the production of G-CSF or similar mediators, and the prognostic significance of this phenomenon.
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PMID:Extreme leucocytosis and splenomegaly in metastasised melanoma. 1536 1

The existence of helper-T cell (Th) subsets, types I and II (Th1/Th2), provides a framework for understanding pathological immune responses. We previously reported that a benzoimidazole derivative, M50367, acted directly on naive Th cells to inhibit their differentiation into Th2 cells. Oral treatment with this compound reduced the Th2 response in vivo and suppressed disease progression in a murine model of atopic asthma. In this study, we investigated the effect of M50367 on 2 other murine disease models, such as atopic dermatitis and intradermal tumor-bearing mice, the pathogenesis of which may be related to the Th2 response. NC/Nga mice treated with a repeated application of picryl chloride developed atopic dermatitis-like skin lesions together with IgE hyper-production. M50367 (30 mg/kg) significantly inhibited the IgE hyper-production without affecting the skin lesions. In C57BL/6 mice bearing intradermal B16F10 melanoma, M50367 (30, 100 mg/kg) significantly inhibited splenomegaly and enhanced spontaneous interferon-gamma release from cultured splenocytes in a dose-dependent manner, though its effect on tumor volume was limited. These results suggest that M50367 could reduce the Th2 response (IgE hyper-production) and enhance the Th1 response (splenocytes interferon-gamma production) in these models. In contrast to previous results in the asthma model, its immunomodulation did not lead to the suppression of disease progression, indicating that the pathogenesis of these models might not simply depend on Th2 response.
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PMID:A novel benzoimidazole derivative, M50367, modulates helper T type I/II responses in atopic dermatitis mice and intradermal melanoma-bearing mice. 1563 67

Paraneoplastic leukemoid reaction (PLR) is a rare condition of leucocytosis in cancer patients. Here we report the rapid progression of a patient suffering from a metastasized malignant melanoma and PLR. The patient's white blood cell count exceeded 200,000 cells per mul and the serum level of Granulocyte Colony-Stimulating Factor (G-CSF) was elevated up to 780 pg/mul. A Tc-m99-labeled anti-NCA90/95 based granulocyte scan demonstrated reactive bone marrow expansion, splenomegaly and granulocyte infiltration into the tumor. KT293, a S100, gp100 and CD68 positive melanoma cell line derived from an axillary metastasis, produced large amounts of G-CSF in vitro and induced rapidly growing tumors and PLR after subcutaneous inoculation in SCID mice. In contrast to G-CSF-secreting cancer cells of other tissue origin, G-CSF-neutralizing antibodies failed to inhibit the growth of KT293 cells. In addition, KT293 cells did not express G-CSF-receptor. These observations suggest that paracrine effects of G-CSF-secretion and PLR might promote an aggressive melanoma phenotype, as seen in this patient.
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PMID:Paraneoplastic leukemoid reaction and rapid progression in a patient with malignant melanoma: establishment of KT293, a novel G-CSF-secreting melanoma cell line. 1566 34

A 71-year-old woman with a history of stage III melanoma was hospitalized for evaluating fever of unknown origin and severe left upper quadrant abdominal pain. A computed tomography scan of the abdomen revealed a solitary lesion in the spleen, 10.5 x 10.4 x 10.1-cm, causing splenomegaly. Fused F-18 FDG PET/CT images revealed a solitary splenic metastasis and a focus of increased uptake in the region of the previously removed melanoma at the right scapula. Based on the clinical findings and CT and PET scans, malignant melanoma (stage IV) was diagnosed. Splenectomy was performed subsequently. The histopathologic finding was consistent with a metastasis of a melanoma.
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PMID:Solitary splenic metastasis in a patient with a malignant melanoma diagnosed with F-18-FDG PET scanning. 1602 64

Although thalidomide (Thd) is being extensively investigated for its effects on cytokine production and T cell costimulation, it is poorly understood whether it is capable of modulating the activities of natural killer (NK) cells. In this study, Thd effects on NK cell activity were examined with a murine model of melanoma, which is mostly rejected by NK cell-dependent mechanism. Administration of Thd significantly (p<0.01 on Day 21) suppressed the growth of subcutaneous B16F1 melanoma. In Thd-treated mice, marked splenomegaly and augmented splenocyte count were observed. Additionally, the percentage of splenic NK1.1+ cells was elevated to approximately 2.5-fold within 10 days after Thd treatment. The expression of interferon inducible protein (IP)-10, interferon (IFN)-gamma, interleukin (IL)-12 and IL-18 was remarkably upregulated. Production of the cytotoxic molecule perforin was also augmented. These data suggest that Thd strongly activates NK cell activity in mice, possibly resulting in enhanced tumor surveillance defense.
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PMID:Thalidomide suppresses melanoma growth by activating natural killer cells in mice. 1708 43

Interferon-alfa (IFN-alpha) is used in patients with various inflammatory and neoplastic disorders. We recently encountered fluorodeoxyglucose (FDG) uptake in generalized lymphadenopathy, splenomegaly, and the marrow in a patient receiving high dose interferon-alpha-2b (IFN-alpha) as adjuvant therapy for the treatment of malignant melanoma. Biopsy of an enlarged hypermetabolic axillary lymph node revealed only a reactive node. Discontinuation of IFN-alpha caused regression of splenomegaly and lymphadenopathy within 3 months.A marrow "hyperstimulation" pattern that can include the spleen is a well-recognized phenomenon on (fluorodeoxyglucose) FDG positron emission tomography/computed tomography (PET/CT) scans in patients receiving chemotherapeutic agents like interferon, though classically due to colony stimulating factors, but does not generally include lymphadenopathy. This case, which likely reflects an interferon-induced pseudolymphoma, highlights the importance of a drug history and clinical correlation for the proper interpretation of FDG PET/CT scans.
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PMID:PET positive generalized lymphadenopathy and splenomegaly following interferon-alfa-2b adjuvant therapy for melanoma. 1788 61


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