[Oat-cell carcinoma of the esophagus: presentation of two cases and literature review]. / Carcinoma oat-cell de esófago: presentación de dos casos y actualización bibliográfica.

OBJECTIVE: Our objective is to contribute an updated view on a condition as rare as oat-cell carcinoma of the esophagus by reviewing the literature and reporting two recent patients seen in our department. MATERIAL AND METHOD: A retrospective study with a review of all medical records of patients seen in our ward and diagnosed with esophageal neoplasm for 6 years (January 2000 to December 2006). RESULTS: 249 cases of esophageal neoplasms were found, of them 106 were of squamous ancestry (42.6%), 141 were adenocarcinomas (56.6%), and 2 were oat-cell carcinomas (0.8%). Only in 45 (18%) was surgical resection feasible, 23 underwent palliative surgery (endoprostheses, gastrostomies, and jejunostomies not included) (9.3%), and the rest (181 cases, 72.7%) received derivative surgery or no surgery at all. CONCLUSIONS: We can affirm that this neoplasm is highly aggressive, displaying in practically all cases dissemination to other sites; this is a rare cancer that mainly affects men and whose clinical picture is similar to that of other malignancies involving the esophagus.

[Embolism caused by a bullet. Report of a case and review of the literature]. / Embolismo por proyectil de arma de fuego. Reporte de un caso y revisión de la literatura.

We describe the case of a 23 years old male, who suffered a 45 bullet wound in the arm and upper right hemithorax. He walked after his injury and 10 minutes later presented dizziness, cough and tachycardia. On admission a minor haemothorax was seen on a chest X ray, but the bullet was not seen. Even without symptoms, an X ray of abdomen showed the missile lying above the left sacroiliac joint. A chest tube was placed, the patient had an excellent recovery and was discharged a week later. After several months he presented hemoptysis and a moderate pain on his right chest and was treated as an acute bronchitis. Six months after his initial injury he developed a florid picture of acute pulmonary embolism (chest pain, dyspnea, hemoptysis, tachycardia, severe cough). A new chest X ray was done and the bullet was shown lying in the right chest. A pulmonary arteriography located it in a lower basal branch. Through a posterolateral thoracotomy the slug was obtained. The recovery was uneventful and he has remained well since. We discuss the possible mechanisms to explain the entrance of the bullet into the vascular system and conclude that in cases of gunshot wounds: a) An exit wound must be always searched for; if not found exploratory X ray are mandatory, b) If the bullet is not found, specially after thoracic injuries, bullet embolism should be contemplated, c) If there are signs of regional ischemia arteriography is mandatory.(ABSTRACT TRUNCATED AT 250 WORDS)

Physical-chemical properties shared by compounds that modulate multidrug resistance in human leukemic cells.

Multidrug resistance (MDR), typified by resistance to Vinca alkaloids and anthracyclines, is a well characterized experimental phenomenon that may have some clinical correlates. Verapamil, chloroquine, and related drugs have been shown previously to be capable of enhancing anticancer drug cytotoxicity in multi-drug-resistant cells, but the mechanism(s) by which these agents do this is(are) unclear. Since these agents did not seem to have common features, we studied these and other compounds for their ability to "modulate" Vinca alkaloid resistance in order to determine whether they possessed any common chemical or physical features. In addition to verapamil, 24 compounds, consisting of indole alkaloids, lysosomotropic agents, and amines, were tested for their ability to enhance the cytotoxicity of vinblastine and/or vincristine in our human leukemic multidrug-resistant cell line, CEM/VLB100. Seventeen compounds that enhance the cytotoxicity of the Vinca alkaloids by more than 5-fold have been identified. These include quinolines (chloroquine, quinine, chinchonidine, and primaquine), acridines (acridine, acridine orange, and quinacrine), and indole alkaloids (yohimbine, corynanthine, reserpine, physostigmine, and the vindoline and catharanthine moieties of the Vinca alkaloids), as well as other alkaloids and amines (chlorpromazine, propranolol, atropine, and tryptamine). Vindoline, catharanthine, and quinacrine also enhanced the cytotoxicity of doxorubicin and teniposide in these cells, indicating that this "modulation" was not limited to Vinca alkaloids. We examined some well known lysosomotropic compounds (methylamine, epinephrine, suramin, and trypan blue) and found that they were not able to enhance the cytotoxicity of vincristine in the CEM/VLB100 cells, indicating that lysosomotropic activity per se is not required for modulator activity. Three-dimensional computer modeling permitted molecular comparisons of conformationally related congeners of vinblastine, vindoline, and verapamil and revealed three regions of structural homology. We measured the hydrophobicity (by oil/water partitioning) and calculated the molar refractivity (by the additive substituent constant method) of active and inactive compounds. We found that those cationic agents--verapamil, quinacrine, indole alkaloids, and quinolines--that were lipid soluble at physiologic pH and had similar molar refractivities were best able to enhance the cytotoxicity of the Vinca alkaloids in our multidrug-resistant cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Preclinical evaluation of illudins as anticancer agents.

Illudins are low molecular weight natural products which were previously evaluated as anticancer drugs using rodent tumor models. In the present studies, we used in vitro cultures of human cancer cells to reevaluate their potential as anticancer agents. Using continuous exposure, Illudins S and M were cytotoxic to human leukemia cells at concentrations of 6-100 nM, but dihydroilludin M was 3 orders of magnitude less toxic, thus identifying a ketone site as a structural feature critical for cytotoxicity. Cytokinetic studies showed that illudin S caused a complete block at the G1-S phase interface of the cell cycle. Kinetics of inhibition of radiolabeled thymidine, uridine, and leucine incorporation suggested a primary effect on DNA synthesis. In colony and liquid culture assays, cell killing was time dependent but near maximal with a 2-h exposure. Myeloid and T-lymphocyte leukemia cells were most sensitive (50% inhibitory concentration, 6-11 nM), but B-cell leukemia/lymphoma, melanoma, and ovarian carcinoma cells were at least 10 times more resistant. Bone marrow granulocyte/macrophage progenitors showed intermediate sensitivity. Illudin S was equally effective against CEM T-lymphocyte leukemia cells expressing the multidrug resistance phenotype associated with Mr 180,000 glycoprotein and the parental cell line. CEM cells resistant to doxorubicin, epipodophyllotoxins, and 1-beta-D-arabinofuranosylcytosine showed only a 2-fold increased resistance to illudin S. Illudins are novel and potent cytotoxins which may be preferentially active against human myeloid and T-cell leukemias, including cells resistant to more conventional chemotherapeutic agents. The present studies illustrate the breadth of information which can be obtained on a new agent using present in vitro screening procedures and human cells.

Chloroquine enhancement of anticancer drug cytotoxicity in multiple drug resistant human leukemic cells.

Vinblastine-sensitive (CCRF-CEM) and -resistant (CEM/VLB100) human T-cell lymphoblasts were treated with the lysosomotropic agent chloroquine. As measured by growth inhibition, this drug enhanced the cytotoxicity of vinblastine in the CEM/VLB100 cells but was less effective in the CCRF-CEM cells. Chloroquine also enhanced the cytotoxic activity of vincristine, daunorubicin and doxorubicin and, to a lesser extent, teniposide (VM-26) in the CEM/VLB100 cells. Histological examination revealed that the vinblastine-resistant cells contained more cytoplasmic vacuoles than their drug-sensitive counter-parts. When the CEM/VLB100 cells were treated with chloroquine, vinblatine, or a combination of the two, the cells displayed many more cytoplasmic vacuoles than the controls. Coincident with the increased number of vacuoles, these treated cells stained more intensely than controls for the lysosomal enzyme, acid phosphatase, but not for lipid. The vacuolization did not increase as much in the CCRF-CEM cell line when these cells were exposed to the chloroquine + vinblastine combination. Vacuolization was also associated with vincristine, doxorubicin, and daunorubicin treatments, but not with VM-26. We conclude that chloroquine is a modulator of anticancer drug action in the CEM/VLB100 cell line.