losartan-potassium and Mouth-Neoplasms

Tumoral microenvironments play a key role in the evolution of solid tumors. Tumor hypoxia is actively involved in the promotion of genetic instability, the invasive capacity of tumor cells, metastasis, and a worsening of the clinical evolution. Endogenous hypoxia markers are controlled by hypoxia-related genes, formed by HIF-1, which is related to several target genes that involve the energy metabolism, angiogenesis, and transmembrane carbonic anhydrases (CAs), mainly CA-IX that is one of the tumor-related carbonic anhydrases. The goal of this paper is to establish the role of CA-IX as a hypoxia marker in OSCC, while analyzing its expression in this type of tumors and its relationship with several clinical and pathological parameters and prognosis, evaluating its relationship with angiogenesis, other hypoxia markers, and clarifying its role in chemotherapy and radiotherapy resistance.

Topics: Antigens, Neoplasm; Antineoplastic Agents; Carbonic Anhydrase IX; Carbonic Anhydrases; Carcinoma, Squamous Cell; Drug Resistance, Neoplasm; Erythropoietin; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Glucose Transporter Type 1; Head and Neck Neoplasms; Humans; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Ki-67 Antigen; Mouth Neoplasms; Neovascularization, Pathologic; Radiation Tolerance; Receptors, Erythropoietin

To evaluate erythropoietin-producing hepatocellular carcinoma (Eph)/Eph receptor-interaction protein (ephrin) expression in oral squamous cell carcinoma (OSCC) and oral epithelial precursor lesions (OEPLs), EphA2, EphB4, and ephrinB2 were examined and compared with microvessel density (MVD) and lymphatic vessel density (LVD). Samples from 73 OSCC and 43 OEPLs patients were immunohistochemically analyzed with antibodies against EphA2, EphB4, ephrinB2, CD34, and D2-40. Results were compared with clinicopathological findings. Immunohistochemical reactivity for EphA2, EphB4, and ephrinB2 was detected in epithelial cells and some stromal vascular cells in OEPLs and OSCC, proportionately with the level of malignancy. The number of blood vessel endothelial cells stained with CD34 and lymphatic vessel endothelial cells stained with D2-40 was increased in OEPLs and OSCC. In OSCC, ephrinB2 and EphB4 exhibited significant correlation with recurrence and invasion depth, respectively. MVD was significantly lower in slight lymphocytic reaction than in prominent stromal reaction. Association was found between LVD and T classification, postoperative metastasis, survival, mode of invasion, and invasion depth. Expression of EphA2, EphB4, ephrinB2, MVD, and LVD might be associated with malignant potential of the oral epithelium. Angiogenesis and lymphangiogenesis appear to be related to progression of potentially malignant oral lesions.

Topics: Carcinoma, Squamous Cell; Endothelial Cells; Ephrins; Erythropoietin; Humans; Mouth Neoplasms; Neoplasm Recurrence, Local

Treatment of anaemia with recombinant human erythropoietin beta (rHuEpo) in patients with squamous cell carcinoma of the head and neck (HNSCC) undergoing curative radiotherapy does not improve cancer control. In fact, incompletely resected patients with HNSCC receiving radiation in combination with rHuEpo showed poorer loco-regional progression-free survival than patients receiving radiation in combination with placebo. It could be hypothesized that the effects of rHuEpo on tumour cell growth might only be manifested in vivo and after cell trauma, and that treating anaemia with rHuEpo might contribute to poor outcome after incomplete surgical resection.. The aim of the present study was to examine the effect of rHuEpo alone and in combination with surgical trauma on the growth of human squamous cell carcinoma in vivo, xenografted onto nude mice.. The surgical trauma was inflicted through subcutaneous transection of the tumour with a needle. Immunohistochemical staining verified expression of the EPO receptor in tumour cells.. rHuEpo alone had no effect on the growth of xenografted HNSCC. However, a significant increase in tumour growth was observed after surgical trauma in combination with rHuEpo compared with surgery alone (p = 0.0008).

Topics: Animals; Carcinoma, Squamous Cell; Cell Division; Cell Transformation, Neoplastic; Cheek; Erythropoietin; Humans; Mice; Mice, Nude; Mouth Neoplasms; Neoplasm Recurrence, Local; Neoplasm Transplantation; Recombinant Proteins; Xenograft Model Antitumor Assays

The majority of Jehovah's Witnesses refuse blood product transfusion, even when it can be lifesaving. Treatment with recombinant human erythropoietin (RHuEPO) is a valuable adjunct in Jehovah's Witness patients undergoing surgery. A number of additional strategies, including acute normovolaemic haemodilution, intra-operative blood salvage and reinfusion, iron and folate supplementation are also utilized to avoid blood transfusion. Critically ill patients have blunted erythropoietin production and decreased endogenous iron availability. This case report reviews the treatment of anaemia in critically ill Jehovah's Witness patients after surgery and discusses the potential need for higher RHuEPO dosing strategies and longer duration of therapy.

Topics: Aged; Anemia; Blood Loss, Surgical; Carcinoma, Adenoid Cystic; Erythropoietin; Female; Hematocrit; Humans; Jehovah's Witnesses; Mouth Neoplasms; Recombinant Proteins; Religion and Medicine

We assessed the influence of hemoglobin level and r-HuEPO administration on response to chemoradiotherapy, locoregional tumor control, and overall survival in patients treated with neoadjuvant chemoradiotherapy and surgery for a squamous cell carcinoma of the oral cavity or oropharynx.. The 191 study patients were treated with mitomycin C (15 mg/m(2) day 1), 5-fluorouracil (750 mg/m(2)/day, days 1-5), and radiotherapy (50 Gy in 25 fractions weeks 1-5), followed by resection of the primary tumor bed and neck dissection at the General Hospital Vienna, Austria, between November 1989 and October 1998 for a T2-4, N0-3, M0 SCC of the oral cavity or oropharynx. Starting in May 1996, patients with a low hemoglobin (Hgb) before or during chemoradiotherapy received r-HuEPO 10,000 IU/kg s.c. 3-6 times/week until the week of surgery.. On multivariate analysis, Hgb level and use of r-HuEPO were independent prognostic factors for response to chemoradiotherapy and locoregional tumor control (p < 0.01). Pathologic response to neoadjuvant therapy was also predictive of locoregional control (p < 0.001). Patients with a pretreatment Hgb > or = 14.5 g/dL had significantly higher complete response, locoregional control, and survival rates than the patients with a pretreatment Hgb < 14.5 g/dL who did not receive r-HuEPO (p < 0.05). The response, control, and survival rates in patients with a pretreatment Hgb < 14.5 g/dL given r-HuEPO were significantly higher than in low Hgb patients not given r-HuEPO (p < or = 0.001) and equivalent to patients with a pretreatment Hgb > 14.5 g/dL (p > or = 0.3).. Low pretreatment Hgb is a negative prognostic factor for oral cavity and oropharyngeal SCCA patients, but was completely abrogated by r-HuEpo administration during neoadjuvant chemoradiotherapy. Randomized trials of radiation and/or chemotherapy with or without r-HuEPO for patients whose Hgb level is either low at the start of therapy or is anticipated to become low during therapy are indicated.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Erythropoietin; Female; Fluorouracil; Hemoglobins; Humans; Male; Middle Aged; Mitomycin; Mouth Neoplasms; Neoadjuvant Therapy; Neoplasm Staging; Oropharyngeal Neoplasms; Preoperative Care; Recombinant Proteins; Retrospective Studies

The authors related about a peculiar form of anemia found in some patients operated on oral cancer; these patients had an almost normal hematic situation before their operation. 63 patients, operated in the course of a year for oral cancer, have been studied by the authors; they have found in 14 cases (22.2%) a light anemia which regressed after a self blood transfusion, during the first week after the operation; in other 8 cases (12.7%) the anemia, which was more serious, persisted beyond the 7th day after the operation. Those 8 patients, suffering from more serious and persistent anemia, were treated from 7th to 21st day after the operation with iron, vitamin B12 and folic acid without any improvement. The hematic situation improved about 10 days after the end of treatment, probably as a result of spontaneous renewal of medullar haemopoietic activity. This anemia, is characterized by normochromia, normocytosis, reduced response of reticulocytes, sideropenia and hyperferritinaemia. The authors think that the pathogenesis of anemia after operation in neoplastic patients is caused by medullary insufficiency existing before the operation, connected with reduced erythropoietin production and emphasized by an operation that sometimes cause bleeding. Consequently the authors hypothesis the use of erythropoietin in the therapy of most severe anemia in neoplastic operated patients.

Topics: Anemia; Erythropoietin; Humans; Mouth Neoplasms; Postoperative Complications