Human prostate sphere-forming cells represent a subset of basal epithelial cells capable of glandular regeneration in vivo.

BACKGROUND: Prostate stem/progenitor cells function in glandular development and maintenance. They may be targets for tumor initiation, so characterization of these cells may have therapeutic implications. Cells from dissociated tissues that form spheres in vitro often represent stem/progenitor cells. A subset of human prostate cells that form prostaspheres were evaluated for self-renewal and tissue regeneration capability in the present study. METHODS: Prostaspheres were generated from 59 prostatectomy specimens. Lineage marker expression and TMPRSS-ERG status was determined via immunohistochemistry and fluorescence in situ hybridization (FISH). Subpopulations of prostate epithelial cells were isolated by cell sorting and interrogated for sphere-forming activity. Tissue regeneration potential was assessed by combining sphere-forming cells with rat urogenital sinus mesenchyme (rUGSM) subcutaneously in immunocompromised mice. RESULTS: Prostate tissue specimens were heterogeneous, containing both benign and malignant (Gleason 3-5) glands. TMPRSS-ERG fusion was found in approximately 70% of cancers examined. Prostaspheres developed from single cells at a variable rate (0.5-4%) and could be serially passaged. A basal phenotype (CD44+CD49f+CK5+p63+CK8-AR-PSA-) was observed among sphere-forming cells. Subpopulations of prostate cells expressing tumor-associated calcium signal transducer 2 (Trop2), CD44, and CD49f preferentially formed spheres. In vivo implantation of sphere-forming cells and rUGSM regenerated tubular structures containing discreet basal and luminal layers. The TMPRSS-ERG fusion was absent in prostaspheres derived from fusion-positive tumor tissue, suggesting a survival/growth advantage of benign prostate epithelial cells. CONCLUSION: Human prostate sphere-forming cells self-renew, have tissue regeneration capability, and represent a subpopulation of basal cells.

Amelioration of acquired nasopharyngeal stenosis, with bilateral Z-pharyngoplasty.

Nasopharyngeal stenosis as a postoperative complication following pharyngeal surgery (tonsillectomy/adenoidectomy) is rare and may be difficult to treat. All patients with severe nasopharyngeal stenosis treated at UCLA with a bilateral Z-pharyngoplasty procedure from 1999 to 2006 were studied (n = 6). Degree of pharyngeal stenosis preoperatively and following a bilateral Z-pharyngoplasty was graded 0-4 based on (1) symptomatology (snoring, hyponasal speech, difficulty with nasal breathing, difficulty breathing during exercise, obstructive sleep apnea, daytime fatigue, anosmia, rhinorrea, dysphagia, or difficulty in blowing nose) and (2) measurement of stricture at the time of direct nasolaryngoscopy. Nasopharyngeal stenosis after pharyngeal surgery (adenotonsillectomy--67%, uvuloplasty--17%, pharyngoplasty--17%) failed to be alleviated by a mean of 2.3 procedures (kenalog injection or scar excision) and required corrective bilateral Z-pharyngoplasty a mean of 9.2 months after the original surgery. Symptomatic grading of the nasopharyngeal stenosis improved from a mean score of 3.3 (severe stenosis) preoperatively to a score of 0.2 (minimal to no stenosis) in follow-up. Endoscopic stricture measurement improved from 6.1 x 6.3 mm preoperatively to 28.1 x 39.3 mm in follow-up. Bilateral Z-pharyngoplasty was effective in alleviating severe postsurgical nasopharyngeal stenosis.

Coengagement of CD16 and CD94 receptors mediates secretion of chemokines and induces apoptotic death of naive natural killer cells.

Down-modulation of CD16 (FcgammaRIII) receptors and loss of natural killer (NK) cell function have been observed in oral cancer patients. However, neither the mechanisms nor the significance of the decrease in CD16 receptors have been fully understood. The cytotoxic activity and survival of NK cells are negatively regulated by antibodies directed against CD16 surface receptor. The addition of anti-CD94 antibody in combination with either F(ab')(2) fragment or intact anti-CD16 antibody to NK cells resulted in significant inhibition of NK cell cytotoxic function and induction of apoptosis in resting human peripheral blood NK cells. Addition of interleukin-2 to anti-CD16 and/or anti-CD94 antibody-treated NK cells significantly inhibited apoptosis and increased the function of NK cells. There was a significant increase in tumor necrosis factor-alpha (TNF-alpha) but not IFN-gamma secretion in NK cells treated either with anti-CD16 antibody alone or in combination with anti-CD94 antibodies. Consequently, the addition of anti-TNF-alpha antibody partially inhibited apoptosis of NK cells mediated by the combination of anti-CD94 and anti-CD16 antibodies. Increase in apoptotic death of NK cells also correlated with an increase in type 2 inflammatory cytokines and in the induction of chemokines. Thus, we conclude that binding of antibodies to CD16 and CD94 NK cell receptors induces death of the NK cells and signals for the release of chemokines.

Salvage surgery with free flap reconstruction: factors affecting outcome after treatment of recurrent head and neck squamous carcinoma.

OBJECTIVE: To determine factors predicting the outcome after salvage surgery with microvascular flap reconstruction for recurrent squamous cell cancer (SCC) of the head and neck. STUDY DESIGN: This is a retrospective analysis of patients treated at an academic medical center. METHODS: One hundred six patients underwent salvage surgery and microvascular flap reconstruction after prior unsuccessful cancer treatment using surgery, radiation, or chemotherapy. All patients had a follow-up interval after salvage surgery of at least 24 months unless cancer rerecurrence occurred within 24 months after salvage surgery. Factors including age, sex, comorbidity level, tobacco use, alcohol use, disease-free interval since prior therapy, prior radiation, prior chemotherapy, prior surgery, recurrent tumor T class, recurrent tumor N class, recurrent cancer stage, and tumor location were examined to determine their association with cancer rerecurrence after salvage surgery. Successful treatment was defined as patients who remained free from cancer rerecurrence for a minimum 2 year period after salvage surgery. RESULTS: Advanced recurrent T class (P = .02) was significantly associated with cancer recurrence. Recurrent cancer stage and patient smoking status approached statistical significance (P = .06). CONCLUSION: Patients with recurrent T1 and T2 class are the best candidates for salvage surgery and microvascular flap reconstruction for treatment of recurrent SCC of the head and neck. Patients with T3 and T4 class recurrent cancers and patients who continue to smoke after initial diagnosis and treatment of head and neck SCC are poor candidates to undergo salvage surgery.

Evaluation of hardware-related complications in vascularized bone grafts with locking mandibular reconstruction plate fixation.

OBJECTIVE: To identify the incidence of hardware and bone-healing complications in patients who underwent locking mandibular reconstruction plate (LMRP) fixation of vascularized bone grafts for reconstruction of segmental mandibular defects. DESIGN: Case series. SETTING: Academic tertiary care medical center. PATIENTS: One hundred one patients who had undergone LMRP fixation of vascularized bone grafts for reconstruction of segmental mandibular defects with a minimum follow-up of 6 months. MAIN OUTCOME MEASURES: Association of patient- and defect-related characteristics with the incidence of loose screws, osteosynthesis nonunion, and complications necessitating hardware removal. RESULTS: The incidence of loose screws was 0.8% in 984 locking screws implanted. The incidence of nonunion was 0.7% in 290 osteosyntheses. Overall, 15 of 101 LMRPs (14.8%) were removed because of hardware-related complications, with plate extrusion (n = 10) the most common complication necessitating hardware removal. Pathologic diagnosis (P = .002), previous treatment with hyperbaric oxygen (P < .001), radiation therapy (P < .001), and cancer recurrence (P = .03) were statistically significant predictors of LMRP-related complications at univariate analysis. At multivariate analysis, previous treatment with hyperbaric oxygen (P < .046) remained a statistically significant predictor of LMRP-related complications. CONCLUSIONS: In patients undergoing mandibular reconstruction, LMRPs are highly effective for fixation of vascularized bone grafts, with a high incidence of bone-graft healing and a low incidence of complications related to loose screws. Nevertheless, there remains a 15% incidence of hardware-related complications, most related to hardware extrusion. Previous treatment with hyperbaric oxygen is a statistically significant predictor of LMRP-related complications.

Radiographic assessment of inverted papilloma.

CONCLUSION: Both CT and MRI defined the extent of histologically proven recurrent disease, although it was impossible to radiographically distinguish recurrent disease from postoperative scar tissue or mucoperiosteal thickening. OBJECTIVE: A retrospective analysis of radiographic findings of patients with known inverted papilloma (IP) was performed to identify those characteristics that should prompt preoperative biopsy in patients with polypoid nasal masses. MATERIALS AND METHODS: The radiologic studies from a group of 77 patients with biopsy-proven IP of the nasal cavity or paranasal sinuses were reviewed. Fifty-three computed tomography (CT) scans, 17 cases of plain sinus radiography and 7 cases of magnetic resonance imaging (MRI) were analyzed. RESULTS: Although no preoperative MRI examinations were available for comparison, CT was the most helpful study for evaluation of primary, nonrecurrent inverted papilloma. CT demonstrated disease-related abnormalities in 90% of studies. The finding of frequent unilateral bony remodeling was demonstrated in 43% of scans. Plain sinus X-rays were abnormal in 70% of cases of primary tumor, with all positive studies showing nonspecific unilateral opacification of the maxillary antrum.

Useful landmarks in arytenoid adduction and laryngeal reinnervation surgery.

OBJECTIVE: Knowledge of the location of the muscular process of the arytenoid cartilage and the recurrent laryngeal nerve is essential to performing a successful arytenoid adduction and laryngeal reinnervation surgery. We describe external landmarks useful in locating these structures. STUDY DESIGN: Cadaveric laryngeal dissection. METHODS: Posterior laryngeal dissection was performed in 16 human larynges. The position of the muscular process of the arytenoid was measured bilaterally relative to the inferior and superior borders of the thyroid lamina. The recurrent laryngeal nerve was followed distally from slightly below the level of the cricothyroid joint to its genu where its vertical course changes to an oblique intralaryngeal course. RESULTS: The muscular process of the arytenoid was usually found halfway between the roots of the superior and inferior cornu of the thyroid lamina. The recurrent laryngeal nerve was found just deep to the cricothyroid joint and lateral to the posterior cricoarytenoid muscle. There were no other nerves in this area. CONCLUSIONS: This study finds that the superior and inferior borders of the thyroid lamina are useful intraoperative landmarks to locate the muscular process of the arytenoid. The cricothyroid joint provides a good starting point to locate the recurrent laryngeal nerve, which can be identified slightly deeper between it and the posterior cricoarytenoid muscle.

Photodynamic therapy and tumor imaging of hypericin-treated squamous cell carcinoma.

BACKGROUND: Conventional cancer therapy including surgery, radiation, and chemotherapy often are physically debilitating and largely ineffective in previously treated patients with recurrent head and neck squamous cell carcinoma (SCC). A natural photochemical, hypericin, could be a less invasive method for laser photodynamic therapy (PDT) of these recurrent head and neck malignancies. Hypericin has powerful photo-oxidizing ability, tumor localization properties, and fluorescent imaging capabilities as well as minimal dark toxicity. The current study defined hypericin PDT in vitro with human SCC cells before the cells were grown as tumor transplants in nude mice and tested as a model for hypericin induced tumor fluorescence and PDT via laser fiberoptics. METHODS: SNU squamous carcinoma cells were grown in tissue culture, detached from monolayers with trypsin, and incubated with 0.1 microg to 10 microg/ml of hypericin before exposure to laser light at 514, 550, or 593 nm to define optimal dose, time, and wavelength for PDT of tumor cells. The SCC cells also were injected subcutaneously in nude mice and grown for 6-8 weeks to form tumors before hypericin injection and insertion of fiberoptics from a KTP532 surgical laser to assess the feasibility of this operating room instrument in stimulating fluorescence and PDT of tumors. RESULTS: In vitro testing revealed a hypericin dose of 0.2-0.5 microg/ml was needed for PDT of the SCC cells with an optimal tumoricidal response seen at the 593 nm light absorption maximum. In vivo tumor retention of injected hypericin was seen for 7 to 10 days using KTP532 laser induced fluorescence and biweekly PDT via laser fiberoptics led to regression of SCC tumor transplants under 0.4 cm2 diameter, but resulted in progression of larger size tumors in the nude mice. CONCLUSION: In this preclinical study, hypericin was tested for 514-593 nm dye laser PDT of human SCC cells in vitro and for KTP532 surgical laser targeting of SCC tumors in mice. The results suggest hypericin is a potent tumor imaging agent using this surgical laser that may prove useful in defining tumor margins and possibly in sterilizing post-resection margins. Deeply penetrating pulsed infrared laser emissions will be needed for PDT of larger and more inaccessible tumors.

Hypericin and pulsed laser therapy of squamous cell cancer in vitro.

OBJECTIVE: This in vitro study compares continuous wave and pulsed laser light at longer wavelengths for activation of the phototoxic drug hypericin in human cancer cells. BACKGROUND DATA: Two-photon pulsed laser light now allows high-resolution fluorescent imaging of cancer cells and should provide deeper tissue penetration with near infrared light for improved detection as well as phototoxicity in human tumors. METHODS: Cultured Seoul National University (SNU)-1 tumor cells from a squamous cell carcinoma (SCC) were incubated with hypericin before photoirradiation at four laser wavelengths. Phototoxicity of hypericin sensitized SCC cells was measured by dimethyl thiazoldiphenyl (MTT) tetrazolium bromide cell viability assays and by confocal fluorescence microscopy via 532-nm and infrared two-photon pulsed laser light. RESULTS: Phototoxic response increased linearly with hypericin dose of 0.1-2 microM, light exposure time of 5-120 sec, and pulsed dye laser wavelengths of 514-593 nm. Light energy delivery for 50% cell phototoxicity (LD50) response was 9 joules at 514 nm, 3 joules at 550 nm, and less than 1 joule at the 593 nm hypericin light absorption maxima. Fluorescence confocal microscopy revealed membrane and perinuclear localization of hypericin in the SNU cells with membrane damage seen after excitation with visible 532 nm continuous wave light or two-photon 700-950 nm picosecond pulsed laser irradiation. CONCLUSIONS: Hypericin may be a powerful tumor targetting drug when combined with pulsed laser light in patients with recurrent head and neck SCC.

Microvascular reconstruction after previous neck dissection.

BACKGROUND: Microvascular reconstruction of defects in the head and neck is more challenging in patients who have undergone a previous neck dissection, owing to prior resection of potential cervical recipient blood vessels used for free flap perfusion. OBJECTIVE: To evaluate the reliability and safety of free flap reconstruction in patients with previous neck dissection. PATIENTS AND METHODS: Sixty free flaps were performed in 59 patients with a medical history of neck dissection for head and neck cancer. This included patients undergoing salvage surgery for recurrent cancer as well as patients undergoing secondary reconstruction of cancer surgery-related defects. Flap selection included 25 radial forearm flaps, 20 fibula flaps, 7 rectus abdominis flaps, 7 subscapular system flaps, and 1 iliac crest flap. RESULTS: Recipient vessels were used in the field of previous neck dissection in approximately half the patients with previous selective neck dissection, while contralateral recipient vessels were always used in patients with a history of modified radical or radical neck dissection. Vein grafts were not necessary in any cases. One arterial anastomosis that was created under excessive tension required urgent reoperation and revision, but there were no cases of free flap failure. CONCLUSIONS: Free flap reconstruction of the head and neck is highly successful in patients with a history of neck dissection, despite a relative paucity of potential cervical recipient blood vessels. Heavy reliance on free flaps with long vascular pedicles obviated the need to perform vein grafts in the present series, probably contributing to the absence of free flap failure. Previous neck dissection should not be considered a contraindication to microvascular reconstruction of the head and neck.

Lamina propria replacement therapy with cultured autologous fibroblasts for vocal fold scars.

OBJECTIVES: To develop a canine model of vocal fold scar and to evaluate its treatment with lamina propria replacement therapy using autologous cultured fibroblasts. MATERIALS AND METHODS: Full thickness of the lamina propria layer in canine vocal folds was injured with a laser. Fibroblasts were cultured and expanded in the laboratory from a buccal mucosal biopsy. The scarred vocal folds were treated with 3 weekly injections of fourth, fifth, and sixth passage autologous fibroblasts. Mucosal waves and acoustic parameters were measured at baseline, after scarification, and several months after injection therapy. Histologic evaluation of the vocal folds for fibroblasts, collagen, elastin, reticulin, and hyaluronic acid was performed. RESULTS: Nine beagle dogs were used, and 1 animal served as control. Vocal fold scarring resulted in absent or severely limited mucosal waves and significantly worse acoustic parameters. Significant improvements in mucosal waves and acoustic parameters were obtained after lamina propria replacement therapy. After therapy, mucosal waves became normal in 4 animals and near normal in the other 4. No statistical difference was found in mucosal waves between baseline and post-therapy. All animals tolerated therapy without complications. The treated vocal folds demonstrated an increased density of fibroblasts, collagen, and reticulin, a decreased density of elastin, and no change in hyaluronic acid. CONCLUSIONS AND SIGNIFICANCE: Therapeutic options for vocal fold scars are limited. Lamina propria replacement therapy in the form of autologous cultured fibroblasts improves mucosal pliability and returns normal or near normal mucosal waves in experimentally scarred vocal folds. This novel therapeutic modality may hold new promise for treating vocal fold scars.

Microvascular flap reconstruction of the mandible: a comparison of bone grafts and bridging plates for restoration of mandibular continuity.

OBJECTIVE: To compare the efficacy of vascularized bone grafts and bridging mandibular reconstruction plates for restoration of mandibular continuity in patients who undergo free flap reconstruction after segmental mandibulectomy. Study design and setting A total of 210 patients underwent microvascular flap reconstruction after segmental mandibulectomy. The rate of successful restoration of mandibular continuity in 151 patients with vascularized bone grafts was compared to 59 patients with soft tissue free flaps combined with bridging plates. RESULTS: Mandibular continuity was restored successfully for the duration of the follow-up period in 94% of patients who received bone grafts compared with 92% of patients with bridging mandibular reconstruction plates. This difference was not statistically significant. In patients who received bone grafts, most cases of reconstructive failure occurred during the perioperative period and were due to patient death or free flap thrombosis. In patients who received bridging plates, all instances of reconstructive failure were delayed for several months and were due to hardware extrusion or plate fracture. CONCLUSIONS: Vascularized bone-containing free flaps are preferred for reconstruction of most segmental mandibulectomy defects in patients undergoing microvascular flap reconstruction. However, use of a soft tissue flap with a bridging mandibular reconstruction plate is a reasonable alternative in patients with lateral oromandibular defects when the nature of the defect favors use of a soft tissue free flap. SIGNIFICANCE: Both bone grafts and bridging plates represent effective methods of restoring mandibular continuity following segmental mandibulectomy, with the former being the preferred technique for patients undergoing microvascular reconstruction.

Dacomitinib, an irreversible Pan-ErbB inhibitor significantly abrogates growth in head and neck cancer models that exhibit low response to cetuximab.

Aberrant epidermal growth factor (EGF) signaling is associated with tumor growth in squamous cell carcinoma of the head and neck in humans (HNSCC), and is a major focus of targeted therapy. Cetuximab, a monoclonal antibody against EGFR, has been successful at prolonging survival but has only a 10% tumor shrinkage response rate in a clinical setting. The goal of this study was to compare dacomitinib (PF-00299804), a next generation small molecule tyrosine kinase inhibitor that irreversibly blocks multiple HER family receptors (HER-1 (EGFR), HER-2 and HER-4 tyrosine kinases), to cetuximab, the current FDA approved anti-EGFR medication for HNSCC and erlotinib, an EGFR specific small molecule tyrosine kinase inhibitor. Dacomitinib, erlotinib and cetuximab were tested in a panel of 27 HNSCC cell lines. Treatment with 100 ug/ml of cetuximab or 1 uM of erlotinib inhibited growth by at least 50% in 7/27 cell lines, while treatment with 1 uM of dacomitinib had similar growth inhibition in 17/27 lines. Cell lines representing three levels of sensitivity to dacomitinib were further examined using Western blots, cell cycle and apoptosis analysis. Treatment with 100 nM of dacomitinib reduced EGFR activity and downstream AKT and ERK pathways more effectively than treatment with 100 ug/ml of cetuximab in all ten tested lines. Although both compounds induced apoptosis at similar levels, dacomitinib caused greater G0/G1 arrest. Sensitivity to EGFR blockade was associated with levels of EGFR and ERK and was not associated with common oncogenic mutations and copy number variations. Phosphorylated and total EGFR and ERK levels correlate with sensitivity to both cetuximab and dacomitinib. Three of the four lines in the exquisitely sensitive group had the highest levels of phosphorylated and total EGFR and ERK among the ten lines selected, while the three resistant lines collectively had the lowest levels. Neither pAKT nor tAKT was associated with sensitivity.

Economic advantages to a distraction decision tree model for management of neonatal upper airway obstruction.

BACKGROUND: Neonatal upper airway obstruction demands urgent attention. Tracheostomy can prove to be lifesaving but has morbidities. Recently, the authors found reduced morbidity/mortality when using a distraction decision tree model compared with conventional "case-by-case" management. In this current study, the authors assess the long-term costs of (1) a decision tree model versus conventional treatment and (2) tracheostomy versus distraction osteogenesis. METHODS: An inpatient cost-matrix analysis study on neonates with upper airway obstruction and micrognathia was performed (n=149). In Part I, conventionally treated neonates managed on a case-by-case basis received home monitoring or a tracheostomy. Decision tree model-managed newborns had specialist consultations and diagnostic testing to determine whether home monitoring, tracheostomy, or distraction osteogenesis would be implemented. In Part II, tracheostomy treatment was compared directly to distraction osteogenesis. RESULTS: In Part I (conventional versus decision tree model), taking into account the costs of the distraction, tracheostomy, hospital stay, diagnostic studies, physician fees, and emergency department visits, the total per patient treatment cost was 1.5 greater in the conventional treatment group ($332,673) compared with the decision tree model ($225,998) (p<0.05). In Part II (tracheostomy versus distraction osteogenesis), the total per-patient treatment cost in the tracheostomy group was two times greater than in the distraction group ($382,246 versus $193,128) (p<0.05). CONCLUSIONS: In treating newborns with micrognathia and upper airway obstruction, a decision tree model with mandibular distraction decreases long-term health care costs compared with conventional treatment. Furthermore, when comparing distraction to tracheostomy, similar decreases in long-term health care costs occurred.

Increased lysis of stem cells but not their differentiated cells by natural killer cells; de-differentiation or reprogramming activates NK cells.

The aims of this study are to demonstrate the increased lysis of stem cells but not their differentiated counterparts by the NK cells and to determine whether disturbance in cell differentiation is a cause for increased sensitivity to NK cell mediated cytotoxicity. Increased cytotoxicity and augmented secretion of IFN-gamma were both observed when PBMCs or NK cells were co-incubated with primary UCLA oral squamous carcinoma stem cells (UCLA-OSCSCs) when compared to differentiated UCLA oral squamous carcinoma cells (UCLA-OSCCs). In addition, human embryonic stem cells (hESCs) were also lysed greatly by the NK cells. Moreover, NK cells were found to lyse human Mesenchymal Stem Cells (hMSCs), human dental pulp stem cells (hDPSCs) and human induced pluripotent stem cells (hiPSCs) significantly more than their differentiated counterparts or parental lines from which they were derived. It was also found that inhibition of differentiation or reversion of cells to a less-differentiated phenotype by blocking NFkappaB or targeted knock down of COX2 in monocytes significantly augmented NK cell cytotoxicity and secretion of IFN-gamma. Taken together, these results suggest that stem cells are significant targets of the NK cell cytotoxicity. However, to support differentiation of a subset of tumor or healthy untransformed primary stem cells, NK cells may be required to lyse a number of stem cells and/or those which are either defective or incapable of full differentiation in order to lose their cytotoxic function and gain the ability to secrete cytokines (split anergy). Therefore, patients with cancer may benefit from repeated allogeneic NK cell transplantation for specific elimination of cancer stem cells.

Carcinoma of the prostate presenting as a painful parotid mass with mandibular invasion: a case report.

Prostate cancer metastatic to the parotid gland is exceedingly rare, as only 10 cases have been previously reported in the literature. Symptoms may mimic a parotid infection or suggest a primary parotid tumor. We report a new case of carcinoma of the prostate metastatic to the parotid. The tumor was painful and had invaded the mandible. Fine-needle aspiration of the mass and immunohistochemical staining for prostate-specific antigen confirmed the diagnosis. The patient died 1 month later of an unrelated cause.

Rapid and potent induction of cell death and loss of NK cell cytotoxicity against oral tumors by F(ab')2 fragment of anti-CD16 antibody.

Freshly isolated untreated NK cells undergo rapid apoptosis and lose their cytotoxic function upon the addition of F(ab')2 fragment of anti-CD16 antibodies. Loss of NK cell cytotoxic function after treatment with F(ab')2 fragment of anti-CD16 antibody can be seen against K562 and UCLA-2 oral tumor cells when either added immediately in the co-cultures of NK cells with the tumor cells or after pre-treatment of NK cells with the antibody before their addition to the tumor cells. Addition of Interleukin-2 (IL-2) in combination with anti-CD16 antibody to NK cells delayed the induction of DNA fragmentation in NK cells, and even though decreased cytotoxicity could still be observed against K562 and UCLA-2 oral tumors when compared to IL-2 alone treated NK cells, the cytotoxicity levels remained relatively higher and approached those obtained by untreated NK cells in the absence of antibody treatment. No increases in IFN-gamma, Granzymes A and B, Perforin and TRAIL genes could be seen in NK cells treated with anti-CD16 antibody. Neither secretion of IFN-gamma nor increased expression of CD69 activation antigen could be observed after the treatment of NK cells with anti-CD16 antibody. Furthermore, IL-2 mediated increase in CD69 surface antigens was down-modulated by anti-CD16 antibody. Finally, the addition of anti-CD16 antibody to co-cultures of NK cells with tumor target cells was not inhibitory for the secretion of VEGF by oral tumor cells, unlike those co-cultured with untreated or IL-2 treated NK cells. Thus, binding and triggering of CD16 receptor on NK cells may enhance oral tumor survival and growth by decreased ability of NK cells to suppress VEGF secretion or induce tumor cell death during the interaction of NK cells with oral tumor cells.

Cystic parathyroid presenting as an apparent thyroid goiter.

Parathyroid cysts are rare lesions that can present clinically as low neck masses. The clinical diagnosis of parathyroid cyst can be challenging and requires a high level of suspicion as it often mimics a thyroid nodule. The cyst occasionally can cause compressive symptoms such as dysphagia or dyspnea. When it occurs in the mediastinum, it can cause recurrent laryngeal nerve paralysis. In this report, we present a patient with a hyperfunctional parathyroid cyst in association with a papillary thyroid carcinoma. In addition, we briefly discuss the current literature on parathyroid cyst. This case is unusual in its clinical presentation in that the parathyroid cyst mimicked a thyroid goiter.

Potential contribution of naïve immune effectors to oral tumor resistance: role in synergistic induction of VEGF, IL-6, and IL-8 secretion.

The aim of this study is to identify the phenotype of resistant oral tumors, and to delineate the contribution of immune effectors to resistance of oral tumors. UCLA-1 oral tumors which were resistant to NK cell mediated cytotoxicity secreted increased amounts of IL-6, IL-1beta, GM-CSF, and IL-8 when cultured with or without immune effectors. In addition, the levels of vascular endothelial growth factor (VEGF) secretion in the co-cultures of naïve immune effectors with UCLA-1 rose significantly when compared to tumor cells alone. IL-2 activated NK cells decreased VEGF secretion in all tumor cells. However, NK cells which were induced to undergo cell death with anti-CD16 antibody were not only unable to decrease VEGF secretion, but they also contributed further to the increase in VEGF secretion by oral tumors. Overall, we show in this paper that naïve as well as non-viable immune effectors may contribute to the growth and resistance of oral tumors by triggering the secretion of key tumor cell growth factors.