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

Lewis lung adenocarcinoma growth was retarded by the oral administration of delta9-tetrahydrocannabinol (delta9-THC), delta8-tetrahydrocannabinol (delta8-THC), and cannabinol (CBN), but not cannabidiol (CBD). Animals treated for 10 consecutive days with delta9-THC, beginning the day after tumor implantation, demonstrated a dose-dependent action of retarded tumor growth. Mice treated for 20 consecutive days with delta8-THC and CBN had reduced primary tumor size. CBD showed no inhibitory effect on tumor growth at 14, 21, or 28 days. Delta9-THC, delta8-THC, and CBN increased the mean survival time (36% at 100 mg/kg, 25% at 200 mg/kg, and 27% at 50 mg/kg, respectively), whereas CBD did not. Delta9-THC administered orally daily until death in doses of 50, 100, or 200 mg/kg did not increase the life-spans of (C57BL/6 times DBA/2)F1 (BDF1) mice hosting the L1210 murine leukemia. However, delta9-THC administered daily for 10 days significantly inhibited Friend leukemia virus-induced splenomegaly by 71% at 200 mg/kg as compared to 90.2% for actinomycin D. Experiments with bone marrow and isolated Lewis lung cells incubated in vitro with delta9-THC and delta8-THC showed a dose-dependent (10(-4)-10(-7)) inhibition (80-20%, respectively) of tritiated thymidine and 14C-uridine uptake into these cells. CBD was active only in high concentrations (10(-4)).
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PMID:Antineoplastic activity of cannabinoids. 115 36

A 69-year-old man with an enlarged spleen, found by computed tomography scan to be multicystic, underwent a splenectomy. Pathological examination revealed a Low-grade mucinous cystadenocarcinoma that was histologically analogous to a mucinous tumor of the ovary. The serum level of tumor markers carcinoembryonic antigen (CEA)and CA19-9 were elevated preoperatively and returned to normal after the operation. In the absence of a primary tumor elsewhere, we considered this tumor to be primary in the spleen, and it was presumed that the tumor arose either from invaginated capsular mesothelium of the spleen or from heterotopic pancreatic or enteric tissue within the spleen.
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PMID:Low-grade mucinous cystadenocarcinoma in the spleen. 141 9

Effects of dietary vitamin B6 at levels ranging from deficiency to megadoses on the development of herpes simplex virus type 2-transformed (H238) cell-induced tumors and on in vitro responses relating to cell-mediated immunity were examined. Male BALB/cByJ mice (n = 260), 5 weeks of age, were fed 20% casein diets containing pyridoxine (PN) at 0.2, 1.2 for the control diet, 7.7, or 74.3 mg/kg diet for 4-11 weeks. After 4 weeks of dietary treatment, 120 of the mice received an injection of H238 cells; mice without H238 injection served as controls. At 4, 8, and 11 weeks, animals from each group were euthanized and blood and spleen samples obtained. Mice fed 0.2 mg PN developed mild deficiency symptoms and gained significantly less weight than those fed 1.2-, 7.7-, and 74.3-mg PN diets. Thirteen to 16 days after tumor cell injection, primary tumor incidence was lowest in mice fed 74.3 mg PN; later, incidence among groups was similar. Mice fed 1.2 mg PN had the largest primary tumor volume, the highest incidence of lung metastases, and the greatest number of metastatic nodules per animal at 7 weeks post injection. Overall, lower tumor volumes were found in animals fed 7.7 and 74.3 mg PN (14 and 32% less than the tumor volume for those fed 1.2 mg PN, respectively); mice fed 0.2 mg PN had the lowest tumor volume. Blood and spleen lymphoproliferative response to stimulation by phytohemagglutinin or concanavalin A generally tended to be higher in mice fed 7.7 and 74.3 mg PN as compared to that in animals fed either 0.2 or 1.2 mg PN. However, decreased mitogen-stimulated responsiveness was observed in all animals with progressive tumor growth. Tumor growth also resulted in splenomegaly and increased thymic atrophy. Significant negative relationships between tumor volume and tumor pyridoxal 5-phosphate (PLP) concentrations were observed for 1.2-, 7.7-, and 74.3-mg PN diet groups. These data suggest that high dietary intake of vitamin B6 may have suppressed tumor development by either immune enhancement or PLP growth regulation of this tumor.
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PMID:Suppression of tumor growth and enhancement of immune status with high levels of dietary vitamin B6 in BALB/c mice. 347 3

Natural killer (NK) cell activity of spleen and thymus was studied in Lewis lung carcinoma (3LL)-bearing mice. A high level of hydrocortisone-sensitive NK cell cytotoxicity was found in the thymus after excision of the primary tumor, but not in nonamputated mice. Conversely, splenic NK cell activity was diminished in nonamputated tumor-bearing mice and remained unmodified in amputated tumor-bearing mice. Excision of the primary tumor prevented tumor-induced thymic atrophy and splenomegaly. Histological study of the thymus revealed the presence of metastatic cells within the cortex. These data suggest that NK cells or their precursors are present in the thymus and can be triggered or unmasked in situ by tumor cells migrating from the primary tumor.
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PMID:Studies of the thymus in mice bearing the Lewis lung carcinoma. I. Thymic natural killer cell activity in 3LL tumor-bearing mice. 687 7

In two lines of transgenic rats (pX rats) from WKAH and F344 strains and carrying the HTLV-I pX gene under control of the mouse H-2Kd promoter, mammary carcinomas developed predominantly in females starting at about 5 months of age. The incidence of the tumor reached about 40% when the rats were 12 months old. Histology of the tumor was undifferentiated carcinoma with massive infiltration of granulocytes into the tumor tissue. Systemic granulocytosis and hepato-splenomegaly due to extramedullary granulocytopoiesis were seen in pX rats and nude mice bearing pX mammary tumor. mRNAs of both pX and host genes, Gro and MIP-2, which are granulocyte chemoattractants of the IL-8 family, were highly expressed in the tumor tissue. Since expression and point mutation of several oncogenes and anti-oncogene, related with mammary carcinomas, were not demonstrated, hitherto unidentified novel oncogenic pathways may be transactivated by the pX transgene in these pX rats. pX mammary carcinoma cell lines, which have similar characteristics to the primary tumor, were established and the cells underwent apoptosis under the serum deprived conditions. The pX rats and the pX mammary carcinomas appear to be suitable models for analyses of HTLV-I pX oncogenesis and immune pathogenesis in vivo and in vitro.
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PMID:HTLV-I pX transgenic rats: development of cytokine-producing mammary carcinomas and establishment of the pX mammary carcinoma cell lines. 920 2

A 70-year-old Japanese man presented to our hospital with a 1-month history of progressive general fatigue and anorexia. A physical examination revealed severe anemic condition, mild persistent splenomegaly, and no palpable surface lymph nodes. He had pleural effusion and ascites, though no malignant cells were detected in the effusion. He eventually died without any diagnosis of his disease. Immunohistochemical staining of his tumor after autopsy showed atypical cells that were negative for epithelial membrane antigen (EMA), keratin (AE1/3), keratin-20, vimentin, factor VIII, leukocyte common antigen (LCA/T200; CD45), myeloperoxidase (MPO), terminal deoxynucleotidyl transferase (TdT), lysozyme, CD1a, CD3, CD4, CD10, CD15, CD20 (L26), CD21, CD23, CD34, CD43, CD56, CD68, CD79a, CD138, and EBER-1 in situ. Only a few scattered cells expressed CD30, but they showed no staining for anaplastic large-cell lymphoma kinase (ALK). A few scattered cells expressed S-100 antigen and the majority of cells dominantly expressed dendritic cell-associated antigens (CD35, FDC, Ki-M1p). In conclusion, we found this unknown primary tumor to be consistent with a follicular dendritic cell tumor with anaplastic features.
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PMID:Follicular dendritic cell tumor as an unknown primary tumor. 1738 Apr 43

Sarcoidosis is a granulomatous disease of unknown origin, with pulmonary findings in more than 90% of patients. Extrapulmonary involvement is common and all organs can be involved (especially lymph nodes, eyes, joints, central nervous system) but it is rare to find an isolated extrapulmonary disease (less than 10% of patients). Granulomatous inflammation of the spleen and the liver is common in patients with systemic sarcoidosis, while hepatosplenic enlargement is unusual and splenic involvement rare. We report two cases of systemic sarcoidosis, that onset with splenic and hepatosplenic disease, and one case with splenic sarcoidosis without pulmonary involvement. In the first case a 53-year-old woman with mild abdominal pain underwent sonography and CT, which revealed one hypoechoic/hypodense splenic lesion. Laboratory tests were normal. In order to exclude a lymphoma, splenectomy was performed: histology revealed a sarcoid granuloma. After surgery the patient was asymptomatic and now, after two years, disease is silent. The second case is a 66-year-old woman with a recent weight loss (8 kg in two months) and alterated liver function tests (AST 61 U/l, ALT 72 U/l, Alkaline phosphatase 748 U/l, g-GT 381 U/l). Since she had a familiar history of colon cancer, abdominal US scan, abdominal CT scan and MRI were performed and showed inter-aorto-caval lymphadenopathies and discreet multiple bilobar hepatic and splenic substitutive lesions, with no signs of primary tumor. Upper and lower GI endoscopy, full gynecological workup, complete set of tumor markers, bone marrow biopsy were performed. All resulted negative for neoplasia. Small pulmonary infiltrations were observed on chest-CT scan but cytology on BAL was normal. Infections were also excluded. An exploratory laparotomy showed whitish peritoneal, hepatic and splenic nodules. The histological exam revealed chronic granulomatous lesions typical for sarcoidosis. During a two-year follow-up after the splenectomy the patient feels well without any treatment. The third patient is a 32-year-old woman with mild epigastric pain after meals. Neck-thoracic CT, bone scintigraphy and upper GI endoscopy were negative. Abdominal US and MR showed splenomegaly with multiple splenic lesions. Splenectomy was performed and histological exam showed chronic granulomatous lesions typical for sarcoidosis. Further laboratory tests were normal, except for ACE (66 UI/l). After the surgery ACE became normal and now, three years later, the patient is still asymptomatic. We conclude that hepatosplenic involvement is less rare than it is thought. It is often oligosymptomatic or accompanied with unspecific manifestations and laboratory abnormalities. The diagnosis could be difficult; in fact typical laboratory findings of sarcoidosis such as ACE, lysozyme, calcium, were not diagnostic. Ultrasonography and CT were important but the diagnosis was established only with the histological examination of suspected lesions. This latter required to differentiate liver and/or spleen sarcoidosis from tuberculosis and other infections, primary biliary cirrhosis, metastasis or malignant lymphoma.
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PMID:Atypical sarcoidosis: case reports and review of the literature. 2138 7

Chronic lymphocytic leukemia (CLL) cells are susceptible to oxidative stress. The expanded porphyrin, motexafin gadolinium (MGd), reacts with intracellular reducing metabolites and protein thiols to generate reactive oxygen species (ROS). A phase II trial administered MGd 5 mg/kg/day IV for 5 days every 3 weeks until disease progression to patients with previously treated CLL and small lymphocytic lymphoma. Thirteen patients (median age 66 years) with a median of four prior therapies (range 2-9) were enrolled. Modest anti-tumor activity was seen in three patients, with improvement in lymphocytosis, lymphadenopathy and/or splenomegaly, but no patient achieved a partial or complete response by NCI 96 criteria. Flow cytometry confirmed tumor uptake of MGd. Serial increase in AKT phosphorylation in patient samples following MGd treatment was not observed, suggesting intracellular generation of ROS was not optimal. Therefore, this schedule of administration achieved MGd uptake into primary tumor cells in vivo, but clinical activity was modest.
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PMID:Effects of motexafin gadolinium in a phase II trial in refractory chronic lymphocytic leukemia. 1986 Jun 24

Despite evidence that antitumor immunity can be protective against renal cell carcinoma (RCC), few patients respond objectively to immunotherapy and the disease is fatal once metastases develop. We asked to what extent combinatorial immunotherapy with Adenovirus-encoded murine TNF-related apoptosis-inducing ligand (Ad5mTRAIL) plus CpG oligonucleotide, given at the primary tumor site, would prove efficacious against metastatic murine RCC. To quantitate primary renal and metastatic tumor growth in mice, we developed a luciferase-expressing Renca cell line, and monitored tumor burdens via bioluminescent imaging. Orthotopic tumor challenge gave rise to aggressive primary tumors and lung metastases that were detectable by day 7. Intra-renal administration of Ad5mTRAIL+CpG on day 7 led to an influx of effector phenotype CD4 and CD8 T cells into the kidney by day 12 and regression of established primary renal tumors. Intra-renal immunotherapy also led to systemic immune responses characterized by splenomegaly, elevated serum IgG levels, increased CD4 and CD8 T cell infiltration into the lungs, and elimination of metastatic lung tumors. Tumor regression was primarily dependent upon CD8 T cells and resulted in prolonged survival of treated mice. Thus, local administration of Ad5mTRAIL+CpG at the primary tumor site can initiate CD8-dependent systemic immunity that is sufficient to cause regression of metastatic lung tumors. A similar approach may prove beneficial for patients with metastatic RCC.
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PMID:Eradication of metastatic renal cell carcinoma after adenovirus-encoded TNF-related apoptosis-inducing ligand (TRAIL)/CpG immunotherapy. 2231 40

Adenosquamous carcinoma of the pancreas directly invading surrounding organs is rare. Here, we describe a case of pancreatic adenosquamous carcinoma directly invading the spleen and colon in a 44-year-old man. Imaging examinations revealed a huge heterogeneous mass in the enlarged spleen and a colonic lump, but showed no obvious space-occupying lesion in the pancreas. An exploratory laparotomy revealed that the enlarged spleen, pancreatic tail, and splenic flexure of the colon were firmly attached to one another. Splenectomy combined with resection of the distal pancreas and splenic flexure of the colon was performed. In the distal pancreatectomy specimen, a 0.8-cm solid mass was present in the tail. The tumor contained definite components of both adenocarcinoma and squamous cell carcinoma. The patient died of cachexia five months after admission. This case is unique in that the metastatic tumor involving the spleen was considerably larger than the primary tumor itself.
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PMID:Splenomegaly as the first manifestation of pancreatic adenosquamous carcinoma: a case report. 2386 60


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