Epidermoid Carcinoma News Headlines

BCH, an Inhibitor of System L Amino Acid Transporters, Induces Apoptosis in Cancer Cells.

Biol Pharm Bull. 2008;31(6):1096-1100

Authors: Kim CS, Cho SH, Chun HS, Lee SY, Endou H, Kanai Y, Kim DK

Purpose: L-Type amino acid transporter 1 (LAT1) is highly expressed in cancer cells to support their continuous growth and proliferation. We have examined the effect of 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH), an inhibitor of system L amino acid transporters, and the mechanism by which BCH suppresses cell growth in cancer cells. Methods: The effect of BCH and the mechanism of BCH on cell growth suppression in cancer cells were examined using amino acid transport measurement, MTT assay, DNA fragmentation analysis, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay and immunoblotting. Results: BCH inhibited L-leucine transport in a concentration-dependent manner, and it inhibited cell growth in a time-dependent manner in KB human oral epidermoid carcinoma cells, Saos2 human osteogenic sarcoma cells and C6 rat glioma cells. The formation of a DNA ladder was observed, and the number of TUNEL-positive cells was increased with BCH treatment. Furthermore, the proteolytic processing of caspase-3 in KB and C6 cells and of caspase-7 in KB, Saos2 and C6 cells was increased by BCH treatment. Conclusion: These results suggest that the inhibition of LAT1 activity by BCH leads to apoptotic cancer cell death by inducing intracellular depletion of neutral amino acids necessary for cancer cell growth.

PMID: 18520037 [PubMed - as supplied by publisher]

Cytotoxic activities of trichothecenes isolated from an endophytic fungus belonging to order hypocreales.

Arch Pharm Res. 2008 May;31(5):611-6

Authors: Chinworrungsee M, Wiyakrutta S, Sriubolmas N, Chuailua P, Suksamrarn A

Bioassay-guided fractionation of the extract of the endophytic fungus KLAR 5 belonging to order Hypocreales, which was isolated from the twig of Knema laurina (Blume) Warb., resulted in the isolation of brefeldin A (1), 8-deoxy-trichothecin (2), trichothecolone (3), 7alpha-hydroxytrichodermol (4), and 7alpha-hydroxyscirpene (5). Compound 5 was isolated from natural source for the first time. Compound 1 was very highly active against human epidermoid carcinoma of the mouth, human breast cancer (BC-1), and human small cell lung cancer (NCI-H187) cells whereas compounds 2 and 4 were selectively active against BC-1 and NCI-H187 cells. Compounds 3 and 5 were moderately active against these three cancer cell lines.

PMID: 18481017 [PubMed - in process]

[Occupational exposure to wood dust and nasal sinus cancer.]

Ann Otolaryngol Chir Cervicofac. 2008 Apr 22;

Authors: Fontana L, Liétin B, Catilina P, Devif C, Féneon B, Martin F, Mom T, Gilain L

OBJECTIVES: To determine the clinical, histological, epidemiological and occupational data related to exposure to wood dust in a series of 100 nasal sinus malignant tumors. MATERIAL AND METHODS: We conducted a retrospective and descriptive study of cases diagnosed between 1st January 1981 and 31 December 2000, in the Auvergne region of France. Individual, medical, and occupational data were collected from a questionnaire completed by the patient (or the patient's family in case of death) and from the medical documents available. RESULTS: Forty-six cases (46 men), with an average age of 63+/-9.2 years [range, 43-82], had been exposed to occupational wood dust before the diagnosis. Fifty-four cases (30 men, 24 women), with an average age of 64.3+/-8.7 years [range, 40-96], had never been exposed. The average annual incidence increased, either for the total population or for the two subgroups distinguished on the basis of occupational exposure to wood dust. The majority of the patients presented different functional symptoms at the time of the diagnosis. For the 46 patients exposed to wood dust, the tumors were primarily ethmoid adenocarcinomas (92%). For the 54 non-exposed patients, the tumors observed were mainly epidermoid carcinomas (57%), then adenocarcinomas (15%). On the 46 patients exposed to wood dust, 85% were carpenters or cabinetmakers. For the majority of the patients, wood dust exposure started before the age of 20 (average age: 17+/-4.5) and the longest exposure began before 1981. The exposure time to wood dust before diagnosis was in the majority of cases greater than 20 years (mean exposure time: 37 years+/-11.4). Only 15% were exposed at the time of the diagnosis (mean time between the end of the exposure to the diagnosis was 11 years+/-2.8). Of the 54 non-exposed patients, no professional risk factor was evidenced. CONCLUSION: Epidemiologic data, such as the increasing incidence, and clinical and professional data, such as the occupational exposure to wood dust, were in agreement with the French and European literature. It is still probably too early to appreciate the effectiveness of prevention, established in France since 1980, on nasal sinus tumor incidence.

PMID: 18436189 [PubMed - as supplied by publisher]

Soluble EMMPRIN (extra-cellular matrix metalloproteinase inducer) stimulates the migration of HEp-2 human laryngeal carcinoma cells, accompanied by increased MMP-2 production in fibroblasts.

Arch Histol Cytol. 2008 Apr;70(5):267-77

Authors: Hanata K, Yamaguchi N, Yoshikawa K, Mezaki Y, Miura M, Suzuki S, Senoo H, Ishikawa K

The basement membrane functions as a barrier against the invasion of cancer cells. It is therefore important to investigate the mechanism of basement membrane degradation by matrix metalloproteinases (MMPs). Previously, cancer cells were long considered to be the major source of MMPs; however, current evidence indicates that most MMPs in cancer tissue are produced by stromal rather than cancer cells. A glycoprotein highly expressed on the cancer-cell membrane, EMMPRIN (extra-cellular matrix metalloproteinase inducer), exhibits the potential role of the MMP inductor in stromal cells. Depending on the cell type, EMMPRIN can stimulate the production of MMP-1, MMP-2, and MMP-3. We here report that soluble full-length EMMPRIN is liberated from HEp-2 human laryngeal epidermoid carcinoma cells, probably via microvesicle shedding. Soluble EMMPRIN stimulates human fibroblasts to produce MMP-2, after which the augmented migration of HEp-2 cells occurs, as observed in an invasion chamber assay with separately cultured fibroblasts. An anti-EMMPRIN function-blocking antibody reduced MMP-2 activity in the conditioned medium and inhibited the migration of HEp-2; obviously, EMMPRIN activity contributes to cancer-cell migration. We postulate that soluble EMMPRIN probably triggers the promotion of cancer invasion in vivo.

PMID: 18431027 [PubMed - in process]

[Mouth floor and mobile tongue epidermoid carcinomas thickness: Prognostic value.]

Rev Stomatol Chir Maxillofac. 2008 Mar 5;

Authors: El-Okeily M, El-Bouihi M, Ricard AS, Lefebvre-Majoufre C, Deminière C, Siberchicot F, Zwetyenga N

INTRODUCTION: Most cancers of the oral cavity are epidermoid carcinomas. The prognosis is made on the patient's general health status and the tumoral stage. The UICC TNM staging classification system is one of the most important factors taken in consideration for the prognosis. But this classification in oral epidermoid carcinomas does not include the tumor thickness (except for T4 tumors). Several studies demonstrated that tumor thickness could influence the prognosis in epidermoid carcinoma and other types of cancers. The aim of our retrospective study was to assess the prognostic value of tumor thickness in oral epidermoid carcinoma. PATIENTS AND METHODS: The study included patients with mouth floor or mobile tongue epidermoid carcinoma classified T1N0, T2N0 and T3N0 between 1985 and 2005. All patients were treated with a curative intention. A pathologist analysed the tumor thickness and cervical lymph nodes. All the slides were examined to measure tumor thickness in millimetres. RESULTS: Three hundred and five patient files were reviewed and 124 patients were included, with 94 men (75.8%), and a mean age of 59.3 years (17-93). The mean and median tumor thickness were respectively 7.7 and 6.5mm (0.4-30). The median tumor thickness was chosen for the study. There was a statistically significant link between the five-year probability of global survival and the initial tumor thickness and between neck node invasion and tumor thickness (p<0.05). DISCUSSION: This study suggests that tumor thickness should be taken in consideration in T1N0, T2N0 and T3N0 mouth floor and mobile tongue epidermoid carcinomas. In the future, the clinical evaluation of tumor thickness will help determine the therapeutic management.

PMID: 18328517 [PubMed - as supplied by publisher]

[A novel retinoid CD437 induces apoptosis of human epidermoid carcinoma A431 cells.]

Nan Fang Yi Ke Da Xue Xue Bao. 2008 Mar;28(3):305-8

Authors: Pan M, Peng ZH, Xiao SX, Li XL, Liu Y, Li ZX, Ren JW

OBJECTIVE: To investigate the effect of a novel retinoid CD437 and all-trans retinoic acid (ATRA) in inducing cell apoptosis and inhibiting the proliferation of human epidermoid carcinoma A431 cells and normal human epidermal keratinocytes. METHODS: MTT assay was used to determine the inhibitory effects of CD437 and ATRA on the growth of A431 cells and normal human epidermal keratinocytes, and the cell morphological changes were observed microscopically. Flow cytometry was used to investigate the effect of CD437 and ATRA on the cell cycle and apoptosis. RESULTS: CD437 was more effective than ATRA in inhibiting the proliferation of A431 cells and normal human epidermal keratinocytes. CD437 increased the percentage of sub-G1 populations in A431 cells and induced G1 arrest in normal human epidermal keratinocytes. ATRA appeared to be relatively ineffective for inducing apoptosis in A431 cells as compared to CD437. CD437 did not duce obvious apoptosis in normal human epidermal keratinocytes. CONCLUSION: CD437 is more effective than ATRA in inhibiting the proliferation and inducing apoptosis in A431 cells and shows selective apoptosis-inducing effect against malignant keratinocytes, suggesting its potential in the prevention or treatment of cutaneous carcinoma.

PMID: 18359678 [PubMed - in process]

Safety of repeated administrations of ixabepilone given as a 3-hour infusion every other week in combination with irinotecan in patients with advanced malignancies.

Eur J Cancer. 2008 Feb 26;

Authors: Faivre S, Delbaldo C, Boige V, Pautier P, Soria JC, Namouni F, Peck R, Cohen M, Raymond E

Epothilones are active tubulin-interacting agents that warrant combinations in clinical studies. This phase I combination study explored ixabepilone administered as a 3-h infusion followed by a 90-minute infusion irinotecan, on days 1 and 14 of every 28-day cycle. Forty-one patients received doses of ixabepilone and irinotecan ranging from 15-30 mg/m(2) and 120-180 mg/m(2) every 2 weeks for a total of 173 cycles, respectively. Dose limiting toxicities reported at doses 25 mg/m(2) ixabepilone and 180 mg/m(2) irinotecan consisted of acute grade 3 diarrhoea and asthenia, eventually associated with neutropenia and sepsis, and/or delayed grade 3 peripheral neuropathy. Therefore, the recommended doses were 20 mg/m(2) ixabepilone and 180 mg/m(2) irinotecan. At this dose level, acute side effects were neutropenia, anaemia, nausea-vomiting, diarrhoea, asthenia, and alopecia. Delayed neuropathy was mostly restricted to reversible grade I-II. Pharmacokinetic data suggested no drug-drug interaction. Five objective responses were observed in four patients with lung cancer and one unknown primary epidermoid carcinoma patient. In conclusion, toxicity including peripheral neuropathy was manageable at the recommended doses of 20 mg/m(2) ixabepilone combined with 180 mg/m(2) irinotecan on days 1 and 14 every 28 days. Promising antitumour activity was observed in patients with platinum-pretreated lung cancer.

PMID: 18308561 [PubMed - as supplied by publisher]

Related Articles

Lymphatic mapping and sentinel lymph node biopsy in epidermoid carcinoma of the anal canal.

Eur J Surg Oncol. 2008 Jan 4;

Authors: Gretschel S, Warnick P, Bembenek A, Dresel S, Koswig S, String A, Hünerbein M, Schlag PM

AIM: Although 15-25% of patients with anal cancer present with superficial inguinal lymph node metastases but the routine application of groin irradiation is controversial because of serious side effects. Inguinal sentinel lymph node biopsy (SLNB) can be used to select patients appropriately for inguinal radiation. The study evaluates the efficiency and clinical impact of SLNB. METHODS: Forty patients with anal cancer underwent 1ml Tc(99m)-Nanocolloid injection in four sites around the tumour. Patients with inguinal radio colloid enrichment were selected for sentinel lymph node biopsy (SLNB). Lymph node status was examined by haematoxylin and eosin (H&E) as well as immunohistochemistry-staining. All SLN-positive patients were scheduled for inguinal radiation; SLN-negative patients with T1 and early T2 tumours were not scheduled for inguinal radiation. RESULTS: SLN were detected in 36/40 patients. Three common patterns of lymphatic drainage were observed: mesenterial, iliacal and inguinal. Twenty patients with inguinal SLN underwent SLN-biopsy. 6/20 patients were SLN-positive. In 10/20 patients SLNB altered the therapy plan - four patients with T1-tumours and positive SLN had additional groin irradiation, whereas 6 patients with small T2-tumors and tumour-free inguinal SLN did not undergo inguinal irradiation. CONCLUSIONS: Inguinal sentinel node biopsy in anal cancer is efficient and could assist in the decision for inguinal radiation. The validity and safety of the proposed therapeutic algorithm has to be proven by a larger, prospective study.

PMID: 18178364 [PubMed - as supplied by publisher]

Diverse TNFalpha-induced death pathways are enhanced by inhibition of NF-kappaB.

Int J Oncol. 2007 Dec;31(6):1519-28

Authors: Katdare M, Efimova EV, Labay E, Khodarev NN, Darga TE, Garofalo M, Nakamura S, Kufe DW, Posner MC, Weichselbaum RR

TNFalpha was initially described as inducing necrotic death in tumors in vivo, and more recently as a cytokine that mediates cytoprotection and inflammation. The anti-tumor effects of TNFalpha are poorly characterized because TNFalpha-induced death of human tumor cells has largely been studied in the presence of agents that block transcription or protein synthesis. Also, most reports in model cell systems describe apoptosis within relatively early time points as the principal mode of cell death induced by TNFalpha. We investigated the cytotoxic effects of 10 ng/ml TNFalpha on human tumor cells of different histological types without concomitant exposure to these inhibitors. Eleven of 21 human tumor cell lines underwent TNFalpha-induced cell death which ranged from 41% to complete loss of viability. Only one cell line demonstrated caspase-dependent apoptosis within 24 h. Nine cell lines underwent death between 48 h and 21 days. Seven of these lines underwent caspase-3 independent death consistent with necrosis. One tumor line exhibited characteristics of senescence following TNFalpha exposure. Nine of 9 cell lines activated NF-kappaB following TNFalpha exposure by 24 h. In all cell lines studied, with the exception of the epidermoid carcinoma cell line that underwent early apoptosis, expression of one or more NF-kappaB target genes was demonstrated at 24-96 h. BMS-345541, a specific IKK inhibitor, increased TNFalpha killing in TNFalpha resistant tumor cell lines by increasing apoptosis, suggesting that inhibition of NF-kappaB may be an effective strategy to enhance the tumoricidal effects of TNFalpha.

PMID: 17982679 [PubMed - indexed for MEDLINE]

Related Articles

[Systematic neck dissection in squamous cell carcinoma of the oral cavity]

Ann Otolaryngol Chir Cervicofac. 2007 Dec;124(6):285-91

Authors: Benlyazid A, Sarini J, Marques B, Garrido-Stowhas I, Delord JP, Zerdoud S, Rives M

OBJECTIVES: To evaluate the neck control after prior surgical management of patients with squamous cell carcinoma of the oral cavity and to quantify the ratio of patients among whom neck dissection did not have a real therapeutic value. To discuss the usefulness of the sentinel node biopsy in this group of patients. METHOD: Retrospective analysis of patients with epidermoid carcinoma of the oral cavity who had systematically a neck dissection. RESULTS: Thirty-nine files of patients have been processed. We found 45% patients classified pN0 (among whom about one half where classified pT4). With a mean follow-up of 19 months, we did not find any cervical lymph node relapse. Five patients died (13.5%) without any cervical disease. CONCLUSION: The systematic cervical lymph node dissection remains the most effective means to obtain the neck control of squamous cell cancers of the oral cavity. It however was applied without therapeutic value for 45% of the patients of this series. The validation of the sentinel node concept as a method of cervical staging should make it possible to avoid this surgical procedure in more than one third of the cases.

PMID: 17673159 [PubMed - indexed for MEDLINE]

Human papillomavirus in oral squamous cells carcinoma in a population of 75 Brazilian patients.

Am J Otolaryngol. 2007 Nov-Dec;28(6):397-400

Authors: Soares RC, Oliveira MC, Souza LB, Costa AL, Medeiros SR, Pinto LP

PURPOSE: In the present study, we investigated the presence of human papillomavirus (HPV) DNA and viral types in 75 cases of oral squamous cells carcinoma from Brazil to obtain data that would contribute to a better understanding of the role of HPV in the pathogenesis of this tumor. MATERIALS AND METHODS: DNA was extracted from paraffin-embedded tissue and amplified by polymerase chain reaction using a pair of primers designated PCO3+ and PCO4+ for the detection of a fragment of the human beta-globin gene, followed by polymerase chain reaction for the detection of HPV DNA using a pair of generic primers, GP5+ and GP6+. Viral typing was performed by dot blot hybridization. RESULTS: Human papillomavirus DNA was detected in 18 (24%) of the 75 cases positive for the human beta-globin gene. No significant association was observed between HPV and age, sex, or anatomical location of the tumor. The most prevalent viral type was HPV-18 (77,8%). CONCLUSION: The low frequency of detection of HPV DNA in oral epidermoid carcinomas suggests a possible participation of the virus in the development and progression of only a subgroup of these tumors.

PMID: 17980772 [PubMed - in process]

[Degeneration of dermoid cysts: a case study of malignant transformation.]

Gynecol Obstet Fertil. 2007 Oct 2;

Authors: Argoitia X, Duga I, Labeyrie E, Toledo L, Couteau C, Querleu D

Malignant transformation of ovarian dermoid cyst (mature cystic teratoma) is rare and most often established in postmenopausal women after surgery by sample anatomopathological analysis. We report the case of a 58-year-old woman showing abdominal pain associated with constipation episodes. The diagnosis of dermoid cyst was established upon ultrasonographic and tomodensitometric criteria. Its histopathological analysis confirmed the presence of a well differentiated epidermoid carcinoma. In line with the literature, our study highlights the importance of the age of the patient, the size of dermoid cyst and its growth rate as well as squamous cell carcinoma (SCC) antigen serum level. These date are collected in order to establish a correct diagnosis and provide an appropriate cure. When a cyst is discovered these data must pathological event, mostly observed in menopaused women. Certainty diagnosis is collected in order to establish a correct diagnosis and provide an appropriate cure.

PMID: 17916437 [PubMed - as supplied by publisher]

Related Articles

Evaluation of resveratrol and piceatannol cytotoxicity in macrophages, T cells, and skin cells.

Arh Hig Rada Toksikol. 2007 Sep;58(3):293-304

Authors: Radkar V, Hardej D, Lau-Cam C, Billack B

The cytotoxicity of resveratrol and of piceatannol, a structural analog of resveratrol, was examined in cultured cells. Using a MTT-based assay, which measures the conversion of 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) to a colored formazan product in living cells, resveratrol was found to inhibit the viability of transformed mouse macrophages, tumor-derived human T cells and human epidermoid carcinoma cells in a concentration-dependent manner, with the effect decreasing in the order: T cells (LC50 approximately 27 micromol L(-1), 24 h; approximately 9 micromol L(-1); 48 h)>macrophages (LC50 approximately 29 micromol L(-1), 24 h; 39 micromol L(-1), 48 h)>skin cells (LC50 approximately 91 micromol L(-1), 24 h; approximately 66 micromol L(-1), 48 h). Paradoxically, a high concentration of resveratrol (50 micromol L(-1)) inhibited the proliferation of all three cell types, and a low concentration (5 micromol L(-1)) stimulated the proliferation of macrophages. The viability of macrophages was also decreased by piceatannol in a concentration-dependent manner. The stimulation of macrophages with zymosan lowered the cytotoxicity of both resveratrol and piceatannol. Scanning electron microscopy of cells treated with resveratrol revealed changes in cellular morphology that were consistent with toxicity. In macrophages and skin cells, resveratrol (50 micromol L(-1)) induced a time-dependent increase in reduced glutathione levels but did not alter the background levels of thiobarbituric acid-reactive substances. Taken together, the present data indicate that resveratrol is toxic to cultured macrophages, T cells and skin cells at concentrations>or=25 micromol L(-1), and that the cytotoxicity occurs via a mechanism that does not involve oxidative stress. Furthermore, the degree of toxicity of both resveratrol and piceatannol towards macrophages depends on the activation status of these cells, with zymosan-activated cells appearing more resistant than nonstimulated cells.

PMID: 17913683 [PubMed - indexed for MEDLINE]