amphotericin-b and Adenocarcinoma

Topics: Adenocarcinoma; Amphotericin B; Antifungal Agents; Colonic Neoplasms; Diagnosis, Differential; Gastrointestinal Diseases; Histoplasmosis; Humans; Itraconazole; Male; Middle Aged; Omentum; Peritoneal Neoplasms

Cryptococcosis is an opportunistic fungal infection causes significant disease predominantly in immunocompromised patients. Here we present an excepcional case of disseminated cryptococcosis with pulmonary and cerebral involvement in an immunocompetent patient with no apparent predisposing factors at the time of hospital admission. We described a case of an apparently immunocompetent 66-years old man admitted to hospital with a one-month history of cough, fever and vertigo. During hospitalization, thorax imaging was suggestive of lung metastasis, therefore, he went through several investigations. During hospitalization, he developed neurological symptoms and subsequently underwent a lumbar puncture. Cerebrospinal fluid (CSF) culture was positive for Cryptococcus spp. isolated on Sabouraud's dextrose agar and bird seed agar. In addition, the direct microscopy examination was positive for the India ink test, as well as with the latex agglutination test for cryptococcal polysaccharide antigen (CrAg) in CSF, while serum CrAg was negative. Despite the absence of classic immunocompromising features, he was treated with amphotericin B and fluconazole due to suspected disseminated cryptococcal infection. Later, he was diagnosed with prostatic adenocarcinoma. Upon successful completion of treatment for disseminated cryptococcosis, the patient underwent radical prostate ablation surgery as a treatment forprostatic adenocarcinoma. This exceptional case emphasizes the high degree of suspicion of atypical infections, and in these cases, it is particularly important to consider fungal infections in hitherto healthy patients with no apparent predisposing factors. Although Cryptococcus spp. is predominantly reported in patients with hematological malignancies, cryptococcosis investigation should also be considered as part of the initial workup of patients with a new diagnosis of a solid tumour prior to chemotherapy or radiotherapy.

Topics: Adenocarcinoma; Aged; Amphotericin B; Antifungal Agents; Cryptococcosis; Fluconazole; Humans; Immunocompromised Host; Male; Prostatic Neoplasms

Topics: Adenocarcinoma; Aged; Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Biopsy; Bronchitis; Bronchoscopy; Chemoradiotherapy; Humans; Immunocompromised Host; Lung Neoplasms; Male; Tomography, X-Ray Computed; Tracheitis; Ulcer

A 73-y-old female with a history of adenocarcinoma of colon and refractory anemia developed febrile neutropenia following chemotherapy. Therapy with iv infusion of amphotericin B deoxycholate (AmBd) was initiated on day 8 of hospital admission. Premedications included acetaminophen, diphenhydramine and meperidine. Patient developed rigor, chill and elevated temperature approximately 100 min into the infusion. The infusion was temporarily discontinued and rigors subsided following administration of 25 mg meperidine im. Infusion was continued after cessation of the rigors with no further sequelae. During each infusion of AmBd over the next 3 d, the patient developed rigor, chill and elevated temperature which was managed with meperidine. However, on day 4 she developed respiratory distress, bronchospasm and visible cyanosis with oxygen saturation of 88% while on 2 L oxygen. The infusion was stopped and the symptoms subsided with administration of albuterol via nebulizer. Amphotericin lipid formulation infusion was reinstituted after 3 d because of the patient's worsening clinical status. However, the patient developed severe respiratory distress approximately 130 min into the infusion. The infusion was discontinued and she was treated with albuterol via nebulizer. Itraconazole therapy was instituted without any adverse sequelae. Clinicians should be aware of this potential adverse event since it can occur with all formulation of amphotericin.

Topics: Adenocarcinoma; Aged; Amphotericin B; Anemia; Antifungal Agents; Colonic Neoplasms; Drug Combinations; Female; Fever; Humans; Infusions, Intravenous; Leukemia, Myeloid, Acute; Neutropenia; Phosphatidylcholines; Phosphatidylglycerols; Respiratory Distress Syndrome

An in vitro study of the combined cytotoxicity of either cisplatin (CDDP) or carboplatin and amphotericin B (AmB) was undertaken on a set of different ovarian carcinoma (IGROVI, IGROVI-C10, OAW42) and peritoneal malignant mesothelioma (CFB-CARP1) cell lines and ascitic cells freshly obtained from ovarian cancer patients so as to investigate the possibility of overcoming their resistance to platinum compounds. Growth-inhibition curves obtained 6 days after a 2-h period of exposure to the drugs showed that AmB at 5-10 mg/l allowed a 5- to 10-fold decrease in the 50% growth-inhibitory concentrations (IC50) of CDDP and carboplatin on either sensitive or resistant cells. Intracellular platinum assays with IGROVI cells showed that AmB acted by increasing dramatically the platinum uptake at a proportion that accounted for the increase in cytotoxicity. In the subline IGROVI-C10, a 10-fold resistant subline of IGROVI, AmB at 10 mg/l allowed recovery to the level of sensitivity seen in the parental cell line in the absence of AmB but not to the level observed in the presence of AmB. Acquisition of resistance mechanisms that are independent of the regulation of platinum uptake might be involved in this cell line. Thus, AmB might act by increasing the intracellular concentration of platinum without modifying the resistance mechanism involved downstream. However, in our models an increase in the intracellular level of platinum was always sufficient for the recovery of chemosensitivity in vitro. We also show that the phosphodiesterase inhibiting methylxanthines act synergistically with AmB. The latter drugs are weakly toxic and could also attenuate the nephrotoxicity of AmB.

Topics: Adenocarcinoma; Amphotericin B; Antineoplastic Agents; Carboplatin; Cisplatin; Drug Synergism; Female; Humans; Mesothelioma; Ovarian Neoplasms; Peritoneal Neoplasms; Treatment Outcome; Tumor Cells, Cultured

To explore the mechanism of cisplatin resistance and its reversion in human ovarian cancer.. A cisplatin resistant cell subline of SKOV3, SKOV3/cp, was established, and a xenograft mice model of human ovarian cancer was established by microencapsulation technology. Various biochemical changes and the effects of modulators on the resistance in the model were observed.. The intracellular platinum accumulation. Pt-DNA adducts and interstrand cross links of DNA (ISC) in SKOV3 was 5.1, 2.4 and 4.8 times respectively of those in SKOV3/cp cell line. Amphotericin B (AmB) and Novobiocin (NVB) could raise platinum accumulation and Pt-DNA adducts concentration in SKOV3/cp and this resulted in reversion of cisplatin resistance.. The primary factors resulting in SKOV3/cp resistance to cisplatin are the reduction of intracellular drugs and the augmentation of the ability to remove Pt-DNA adducts. AmB and NVB can reverse cisplatin resistance in SKOV3/cp cells.

Topics: Adenocarcinoma; Amphotericin B; Animals; Antibiotics, Antineoplastic; Cisplatin; DNA Adducts; Drug Resistance, Neoplasm; Female; Humans; Mice; Mice, Inbred BALB C; Neoplasm Transplantation; Novobiocin; Ovarian Neoplasms; Tumor Cells, Cultured

Inherent resistance of colon cancer cells to cis-diamminedichloroplatinum(II) (CDDP) is partly attributed to reduced drug penetration through plasma membrane. Amphotericin B (AmB), a polyene antifungal antibiotic, has been shown to increase CDDP penetration and cytotoxicity on several non-digestive cancer cell lines. We demonstrated here that AmB dramatically increases the penetration of CDDP, and to a lesser extent that of carboplatin (Carbo-P) and oxaloplatin (L-OHP), in the primary resistant HT 29 human colon cancer cells when drug incubation is performed in serum-free medium. The cytotoxicity of CDDP but not that of Carbo-P and L-OHP was increased by AmB. However, AmB-induced potentiation of CDDP penetration and toxicity was almost completely abolished when cell incubation was performed in presence of human serum. We investigated whether the dilution of human serum by a high osmotic power gelatine solution (Lomol) could restore the positive effect of AmB on CDDP accumulation in HT 29 cells. Incubation of cells with CDDP and AmB in pure Lomol resulted in a 6-fold increase in platinum cellular content. However, addition of serum (25%) in Lomol solution reduced to only 2-fold the increase in platinum cellular content provoked by AmB. These disappointing results show that AmB is probably uninteresting as a modulator of CDDP resistance in clinical practice. The use of haemodilution to restore the positive AmB effect on platinum cellular accumulation cannot be warranted.

Topics: Adenocarcinoma; Amphotericin B; Antineoplastic Combined Chemotherapy Protocols; Blood Proteins; Cell Membrane Permeability; Cisplatin; Colonic Neoplasms; Culture Media, Serum-Free; Drug Resistance; Drug Synergism; Humans; Tumor Cells, Cultured

HT 29-D4 is a clonal cell line, derived from the human colon adenocarcinoma cell line HT 29, which can be induced to differentiate into enterocyte-like cells by replacing glucose with galactose in the culture medium (Fantini et al. [1986], J. Cell Sci. 83, 235-249). Both undifferentiated and differentiated HT 29-D4 cells have been successfully grown to confluency in Costar Transwell permeable chambers. Only HT 29-D4 cells grown in glucose-free, galactose-containing medium were able to form leakproof monolayers, as demonstrated by their ability to prevent diffusion of serum proteins. These monolayers consist of highly polarized epithelial-like cells with a well organized apical brush border. Transepithelial electrical parameters have been measured under sterile conditions for both types of monolayer. Only HT 29-D4 monolayers cultured in glucose-free, galactose-containing medium were electrically active, with a transepithelial resistance R = 172 +/- 46 omega.cm2, a potential difference PD = 0.35 +/- 0.05 mV, apical negative and a short-circuit current Isc = 2.0 +/- 0.4 microA.cm-2. Apical addition of amphotericin B induced a rapid and considerable increase in Isc and PD, which was abolished by basal ouabain. In contrast, HT 29-D4 cells grown in glucose-containing medium did not generate any potential difference (PD = 0 mV) and their resistance was very low (R = 34.1 +/- 0.9 omega.cm2). It is concluded from these studies that HT 29-D4 cells grown in glucose-free, galactose-containing medium acquire functional characteristics of epithelia, compared to HT 29-D4 cells grown in glucose-containing medium.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenocarcinoma; Amphotericin B; Cell Differentiation; Cells, Cultured; Galactose; Humans; Intercellular Junctions; Membrane Potentials; Microscopy, Electron; Tumor Cells, Cultured

Human colonic carcinoma Caco-2 cells grown in vitro undergo epithelial differentiation. Electrical measurements showed that they form resistant monolayers of polarized cells. On millipore filters, transepithelial electrical resistance (154 +/- 6.5 omega X cm2) was accompanied by a small potential difference (0.29 +/- 0.02 mV, serosal side positive) and by short-circuit current (1.9 +/- 0.14 microA X cm-2), both of which were ouabain sensitive. Micropuncture of domes formed on plastic supports under standard culture conditions revealed electrical polarity similar to that of filter-grown cells (0.8 +/- 0.2 mV, serosal side positive) combined with a highly negative cytoplasm (-57 +/- 1 mV) and very marked cell asymmetry (76% of total electrical cell resistance was located in the mucosal membrane). These parameters were not affected by the diuretic amiloride nor the hormone aldosterone, suggesting that sodium conductance is very limited in the mucosal membrane. Addition to the mucosal side of the ionophore nystatin or amphotericin B unmasked the possibility of high electrical transport activity. Electrical measurements made it possible to define the epithelial properties of Caco-2 cells, which may resemble those of colonic crypt or fetal cells. These measurements also confirmed that functional differentiation is homogeneous in Caco-2 cells. It is suggested that dome cell micropuncture may be useful in investigating the functional properties of other dome-forming cell lines.

Topics: Adenocarcinoma; Alanine; Aldosterone; Amiloride; Amphotericin B; Cell Differentiation; Cell Division; Cell Line; Cells, Cultured; Colonic Neoplasms; Electric Conductivity; Epithelial Cells; Glucose; Humans; Microelectrodes; Nystatin; Sodium

Eighteen patients with unresectable bronchogenic carcinoma were treated with amphotericin B (7.5 mg/m2 on day 1, 15 mg/m2 on day 2, and 30 mg/m2 on days 3 and 4) plus BCNU (250 mg/m2 on day 4 following amphotericin B) with courses of therapy repeated every 8 weeks. All patients had metastatic disease, and 5 had received prior chemotherapy. Antitumor responses were observed in 8 patients. Six patients had partial responses (greater than 50% decrease in tumor area): 1 of 3 with small cell undifferentiated carcinoma, 1 of 4 patients with large cell undifferentiated carcinoma, 2 of 7 patients with adenocarcinoma, and 2 of 4 patients with epidermoid carcinoma. Two patients had objective improvement (25--50% decrease in tumor area): 1 with small cell undifferentiated carcinoma and 1 with epidermoid carcinoma. The median duration of remission was 3 months. The median duration of survival was 7 months for patients achieving partial response, and only 2 months for other patients. Myelosuppression was the dose limiting toxicity. One patient died with hepatocellular dysfunction, possibly related to BCNU. Transient hypotension was observed in 2 patients. We conclude that amphotericin B plus BCNU produced an encouragingly high response rate in patients with bronchogenic carcinoma, and that a randomized phase III trial is warranted to determine whether amphotericin B enhances the antitumor effects of nitrosoureas or other known antitumor agents.

Topics: Adenocarcinoma; Adult; Aged; Amphotericin B; Bone Marrow; Carcinoma, Bronchogenic; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Carmustine; Drug Evaluation; Drug Therapy, Combination; Female; Humans; Lung Neoplasms; Male; Middle Aged

Topics: Adenocarcinoma; Adult; Amphotericin B; Aspergillosis; Colectomy; Colitis, Ulcerative; Colonic Neoplasms; Humans; Lung Diseases, Fungal; Male; Postoperative Complications; Splenectomy