amphotericin-b and Colonic-Neoplasms

BACKGROUND Mucormycosis is a rare, invasive, and opportunistic fungal infection that occurs in the setting of neutropenia, immune deficiency, solid-organ transplant, and iron overload. The gastrointestinal system is a rare site of mucormycosis, and gastrointestinal mucormycosis is associated with high mortality and accounts for 4-7% of all cases. CASE REPORT We present the case of a 64-year-old hypertensive man with transfusion-dependent myelodysplastic syndrome who underwent renal transplant surgery 11 years ago. He also was taking maintenance Deferasirox for iron overload. He presented with a 2-day history of right lower-quadrant abdominal pain, nausea, vomiting, and non-bloody diarrhea. An abdominal examination revealed guarding and a 5×6 cm mass in the right iliac fossa. A CT scan of the abdomen showed signs of perforation of a cecal mass. As the patient was unstable, emergency right hemicolectomy and end ileostomy were performed. After the surgery, the patient was moved to the Intensive Care Unit (ICU) and a broad-spectrum antibiotic was administered. Histopathological examination results received on postoperative day 5 showed broad pauciseptate hyphae with substantial blood-vessel infiltration, suggestive of mucormycosis. Amphotericin B was started; however, on the same day, his condition deteriorated and he was moved back to the ICU. Despite maximum cardiorespiratory support, he had multiorgan failure and died. CONCLUSIONS Gastrointestinal mucormycosis presentation is non-specific, the diagnosis is often made late or is missed, and mortality remains high. High clinical suspicion, early diagnosis, and combined antifungal and surgical treatment is the best way to reduce mortality and improve survival.

Topics: Amphotericin B; Antifungal Agents; Colonic Neoplasms; Humans; Kidney Transplantation; Male; Middle Aged; Mucormycosis

Gastrointestinal basidiobolomycosis (GIB), a rare fungal infection associated with high mortality, has been reported worldwide mainly from tropical and subtropical regions of Asia, USA, and Latin America. The clinical manifestations are highly diverse and non-specific depending on the underlying disease, but fever, abdominal pain, weight loss, diarrhea, constipation and chills have been observed. There are no prominent risk factors for GIB but climatic conditions and life style are related to this infection in arid and semi-arid regions. Therefore timely diagnosis and early treatment is a challenge. Herein, we present an unusual case of gastrointestinal basidiobolomycosis in a 54-year-old male, initially misdiagnosed as colon cancer. After follow-up, no evidence of relapse and the patient was successfully cured by liposomal amphotericin B. In addition, the differential diagnosis and histopathological findings are discussed with a review of the literature.

Topics: Amphotericin B; Antifungal Agents; Colonic Neoplasms; Diagnosis, Differential; Diagnostic Errors; Diarrhea; Entomophthorales; Gastrointestinal Tract; Humans; Male; Middle Aged; Zygomycosis

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

Primary gastrointestinal infection is an uncommon manifestation of histoplasmosis. It is almost always associated with disseminated disease and/or an immunocompromised host. The ileum and cecum are the most common sites involved. We report two cases of primary gastrointestinal histoplasmosis in HIV-seropositive men who presented with annular constricting right colon lesions.

Topics: Adult; Amphotericin B; Biopsy; Colonic Diseases; Colonic Neoplasms; Diagnosis, Differential; Histoplasmosis; HIV Seropositivity; Humans; Male

Recently, the structure-function relationships between amphotericin B (AmB) and ergosterol have been solved using synthetic techniques that require a mycosamine-mediated direct binding interaction between AmB and ergosterol to form AmB ion channels. However, studies to directly probe the AmB-induced membrane permeability changes have not been conducted. In the present work, we investigate the following fundamental question: does AmB induce concentration- and time-dependent permeability changes across ergosterol-containing membranes? Herein, we employ fluorescent dyes of known average diameter to quantify the diameters of AmB ion channels. In addition, we take a single-particle tracking approach to define the intracellular microrheology in the absence and presence of AmB ion channels. Present results show that increasing AmB concentration tends to increase the preferential accumulation of AmB ion channels in the presence of the excess membrane-embedded ergosterol. We found that AmB induces time-dependent membrane permeability; increases approaching 50% in both the velocity fluctuations and diffusion coefficients of vesicles occur on the same time scale as the efflux of potassium ions (≅30min). Furthermore, we propose a two-dimensional, semi-regular tessellation model to geometrically assess the pore size of the AmB ion channels in response to the AmB dose. This approach offers one possibility for the design of AmB ion channels with tunable aqueous pore size, which could provide an opportunity to replace damaged membrane water channels of the aquaporin family in future applications.

Topics: Amphotericin B; Cell Membrane Permeability; Colonic Neoplasms; Humans; Ion Channels; Polyporaceae; Potassium; Rheology; Tumor Cells, Cultured; Water

Taiwanofungus camphoratus, a well-known Chinese medicine used in Taiwan, possesses several pharmacological functions, including anticancer effects. In the present study, we aimed to investigate a novel anticancer effect by pretreating cancer cells with an ethanolic extract of T. camphoratus (TCEE) followed by the administration of an antifungal agent amphotericin B (AmB). Both TCEE and AmB showed significant dose-dependent cytotoxicity in HT29 cells. Pretreatment with a nontoxic dose of TCEE enhanced the cytotoxicity of AmB. Furthermore, significant apoptotic cell death was found in cells treated with TCEE and AmB. A combination treatment with AmB plus TCEE resulted in a significant repression of tumor growth in HT29 xenografts. Collectively, our results indicated that combined treatment with AmB and TCEE effectively induced apoptosis and inhibited tumor growth. In the future, TCEE may serve as a potential complementary and alternative medicine to treat patients suffering from colorectal cancer.

Topics: Amphotericin B; Animals; Antifungal Agents; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Antrodia; Apoptosis; Colonic Neoplasms; Ethanol; HT29 Cells; Humans; Male; Mice; Mice, Nude; Taiwan; Triterpenes

Although Candida species are present as normal microflora of the human host, alterations in host defenses can lead to development of disease. Candida infections, ranging from urinary tract infections to bloodstream infections, are common in patients in the intensive care unit. Infections with non-albicans Candida sp are becoming more frequent, and resistance among these isolates is concerning. Candida kefyr is an uncommonly documented fungal pathogen. We report two cases of infection resulting from C. kefyr in our institution. The two patients had underlying disease states and drug therapies that increased the likelihood of developing an immunocompromised state. The C. kefyr isolates obtained from both patients were susceptible to amphotericin B, fluconazole, and itraconazole. Both patients had resolution of infection, one after receiving treatment with amphotericin B and the other with voriconazole.

Topics: Adult; Amphotericin B; Antifungal Agents; Budd-Chiari Syndrome; Candidiasis; Colonic Neoplasms; Female; Humans; Male; Middle Aged; Treatment Outcome

Fractionation of a methanol extract of the leaves and twigs of Casearia sylvestris, as directed by activity against KB cell cytotoxicity, led to the isolation of three novel clerodane diterpenoids, casearvestrins A-C (1-3). The structures of 1-3 were deduced from one- and two-dimensional NMR experiments, including relative stereochemical assignments based on ROESY correlations and COSY coupling constants. All three compounds displayed promising bioactivity, both in cytotoxicity assays against a panel of tumor cell lines and in antifungal assays via the growth inhibition of Aspergillus niger in a disk diffusion assay.

Topics: Antifungal Agents; Antineoplastic Agents, Phytogenic; Aspergillus niger; Colonic Neoplasms; Diterpenes; Drug Screening Assays, Antitumor; Ecuador; Female; Humans; Inhibitory Concentration 50; KB Cells; Lung Neoplasms; Magnoliopsida; Molecular Conformation; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Ovarian Neoplasms; Plant Leaves; Plant Shoots; Plants, Medicinal; Spectrophotometry, Infrared; Spectrophotometry, Ultraviolet; Spectroscopy, Fourier Transform Infrared; Tumor Cells, Cultured

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

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

To explore the role of calcium in mediating the action of carbachol in chloride-secreting epithelia, we simultaneously measured intracellular free [Ca] ([Ca]i) and the potassium conductance (gK) of the basolateral membrane in T84 cells grown on collagen-coated filters. [Ca]i was measured with fura-2 and fluorescence microscopy and expressed as a relative value ([Ca]'i) normalized to control. To assess changes in basolateral gK, we measured the short circuit current (Isc) in the presence of luminal amphotericin and a transepithelial mucosa-to-serosa K+ gradient (Germann, W. J., M. E. Lowy, S. A. Ernst, and D. C. Dawson. 1986. J. Gen. Physiol. 88:237-251). Treatment of the monolayers with carbachol resulted in a parallel increase and then decrease in [Ca]'i and gK. The carbachol-induced changes in gK appeared to be dependent on the increase in [Ca]i because stimulation of gK was significantly diminished when the hormone-induced increase in [Ca]'i was blunted, either by loading the cells with BAPTA or by reducing the extracellular [Ca]. The carbachol-stimulated increase in gK appeared to be the direct result of the increase in steady-state [Ca]'i. The changes in gK and [Ca]'i after stimulation with carbachol were correlated and ionomycin also increased gK and [Ca]'i in a parallel manner. The carbachol-induced delta gK per delta[Ca]'i, however, was greater than that after ionomycin. Because ionomycin and carbachol appear to open the same channel, a conclusion based on inhibitor and selectivity experiments, carbachol may have a second action that amplifies the effect of calcium on gK.

Topics: Amphotericin B; Calcium; Carbachol; Cell Membrane; Colonic Neoplasms; Egtazic Acid; Electric Conductivity; Humans; Ionomycin; Microscopy, Fluorescence; Potassium; Tumor Cells, Cultured

Topics: Amphotericin B; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Renal Cell; Colonic Neoplasms; Drug Evaluation; Humans; Kidney Neoplasms; Lomustine; Pilot Projects; Rectal Neoplasms

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

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

Topics: Amphotericin B; Biological Transport; Carcinoma, Squamous Cell; Carrier Proteins; Cells, Cultured; Colonic Neoplasms; Female; Humans; Kinetics; Mechlorethamine; Neoplasms, Experimental; Ovarian Neoplasms; Stimulation, Chemical