Efficacy and Safety of Suprachoroidal CLS-TA for Macular Edema Secondary to Noninfectious Uveitis: Phase 3 Randomized Trial.

PURPOSE: Injection of pharmacotherapy into the suprachoroidal space, between the sclera and choroid, is an alternative delivery technique developed with the rationale of providing higher drug concentrations to posterior ocular structures compared with other intraocular and periocular injection procedures. This study was conducted to evaluate the safety and efficacy of suprachoroidally injected triamcinolone acetonide formulation (CLS-TA), a suspension of triamcinolone acetonide, in improving vision among patients with noninfectious uveitis complicated by macular edema (ME). DESIGN: Phase 3 masked, randomized trial. PARTICIPANTS: One hundred sixty patients with ME secondary to noninfectious uveitis. Patients were required to have a best-corrected visual acuity (BCVA) of 5 or more Early Treatment Diabetic Retinopathy Study (ETDRS) letters (Snellen equivalent, 20/800) and 70 or fewer ETDRS letters read (Snellen equivalent, 20/40) in the study eye. METHODS: Patients were randomized 3:2 to suprachoroidally injected CLS-TA or sham treatment, with administrations at day 0 and week 12. MAIN OUTCOME MEASURES: The primary end point was improvement from baseline of 15 or more ETDRS letters in BCVA at week 24. The secondary end point was reduction from baseline in central subfield thickness (CST) at week 24. RESULTS: In the CLS-TA arm, 47% of patients gained 15 or more ETDRS letters in BCVA versus 16% in the control arm (P < 0.001), meeting the primary end point. Mean reductions in CST from baseline were 153 µm versus 18 µm (P < 0.001). No serious adverse events (AEs) related to treatment were reported. Corticosteroid-associated AEs of elevated intraocular pressure occurred in 11.5% and 15.6% of the CLS-TA and control groups, respectively. Cataract AE rates were comparable (7.3% and 6.3%, respectively). CONCLUSIONS: Patients in the CLS-TA study arm experienced clinically significant improvement in vision relative to the sham procedure, demonstrating the efficacy of suprachoroidal injection of CLS-TA for the treatment of ME in a vision-threatening disorder.

SUPRACHOROIDAL INJECTION OF TRIAMCINOLONE ACETONIDE, CLS-TA, FOR MACULAR EDEMA DUE TO NONINFECTIOUS UVEITIS: A Randomized, Phase 2 Study (DOGWOOD).

PURPOSE: Evaluate a single suprachoroidal injection of a proprietary triamcinolone acetonide suspension, CLS-TA, in subjects with macular edema due to noninfectious uveitis. METHODS: Randomized, controlled, masked Phase 2 study. Safety and efficacy of a single suprachoroidal injection of CLS-TA (4.0 and 0.8 mg in a 4:1 ratio) were assessed at 1 and 2 months after injection. The primary efficacy endpoint was change in central subfield thickness from baseline to Month 2, assessed by spectral domain optical coherence tomography. RESULTS: Twenty-two adults were enrolled. The primary endpoint was met in subjects who received suprachoroidal injection of CLS-TA 4.0 mg, mean central subfield thickness significantly decreased from baseline by 135 µm and 164 µm at Month 1 (P = 0.0056) and Month 2 (P = 0.0017), respectively. At Month 2, 69% of subjects who received 4.0 mg experienced ≥20% reduction in central subfield thickness, and 65% had improvement of best-corrected visual acuity of ≥5 Early Treatment Diabetic Retinopathy Study letters, with a mean improvement of 9.2 letters (P = 0.0004). Safety analyses supported acceptable safety/tolerability, with no corticosteroid-related increases in intraocular pressure. CONCLUSION: A single suprachoroidal injection of CLS-TA (4.0 mg; 0.1 mL) in subjects with macular edema due to noninfectious uveitis was well-tolerated, significantly reduced central subfield thickness from baseline at 2 months, and significantly improved visual acuity.

Medial Approach for the Resection of Goiters with Suprahyoid, Retropharyngeal, or Substernal Extension.

BACKGROUND: Resection of massive goiters with suprahyoid, retropharyngeal, and substernal extension may not be amenable to standard approaches. This study evaluates a surgical approach allowing resection of massive goiters with minimal substernal and deep neck dissection. METHODS: Cases of thyroidectomy for goiters with substernal, retropharyngeal, or suprahyoid extension at a single institution from 2006 to 2017 were reviewed. The technique involves initial complete division of the medial thyroid tracheal attachments after identification of the RLN medial-inferiorly or superiorly. Deep components are then delivered into the superficial paratracheal region of the neck. RESULTS: Sixty patients were included, 46 of which had substernal and 14 had only suprahyoid or retropharyngeal extension. Mean substernal extension was 3.7 cm (range 1.5-7.5 cm). The medial approach was successful in identifying the RLN in 70 (83%) of 84 goiter sides (71% medial-inferiorly and 29% superiorly). Standard inferior/lateral approaches were used in 12 (14%) nerves or not found until after goiter removal in 2 (2.5%). No patients required sternotomy or tracheotomy. Complications included postoperative seroma/hematoma (n = 9, 15%) with one re-exploration, transient RLN injury (n = 4, 4% of all lobectomies), transient hypocalcemia (n = 6, 16% of total thyroidectomies), permanent hypocalcemia (n = 2, 5% of total thyroidectomies), and permanent RLN paralysis (n = 1, 1% of all lobectomies). CONCLUSION: Large suprahyoid, retropharyngeal, and substernal goiters were resected transcervically with low morbidity. Early complete division of Berry's ligament after medial-inferior RLN identification was achieved in a high proportion of patients, facilitating goiter delivery with minimal mediastinal and deep neck dissection.

Longitudinal Vision-Related Quality of Life for Patients with Noninfectious Uveitis Treated with Fluocinolone Acetonide Implant or Systemic Corticosteroid Therapy.

PURPOSE: To evaluate longitudinal vision-related quality of life (VRQoL) in patients with noninfectious uveitis. DESIGN: Cohort study using randomized controlled trial data. PARTICIPANTS: Patients with active or recently active intermediate uveitis, posterior uveitis, or panuveitis enrolled in the Multicenter Steroid Treatment Trial and Follow-up Study. METHODS: Data from the 25-item National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25) for the first 3 years after randomization were evaluated semiannually. Analyses were stratified by assigned treatment (129 implants vs. 126 systemic therapies) because of substantial differences in the trajectories of VRQoL. The impact of baseline measurements of visual function (visual acuity and visual field), demographics, and disease characteristics was assessed using generalized estimating equations. MAIN OUTCOME MEASURES: Primary outcome was the NEI-VFQ-25 composite score over 3 years after randomization. RESULTS: Individuals in both treatment groups showed similar improvement in NEI-VFQ-25 scores after 3 years of follow-up (implant: 11.9 points; 95% confidence interval [CI], 8.6-15.2; P < 0.001; systemic: 9.0 points; 95% CI, 5.6-12.3; P < 0.001; P = 0.21 for interaction). Individuals in the implant group showed a substantial improvement during the first 6 months followed by stable scores, whereas individuals in the systemic group showed a steady improvement over the course of follow-up. Worse initial visual acuity and visual fields were associated with lower initial NEI-VFQ-25 scores for both treatment groups. In the systemic group, these differences were maintained throughout follow-up. In the implant group, individuals with initial visual acuity worse than 20/40 showed additional improvement in NEI-VFQ-25 score to come within -7 points (95% CI, -15.0 to 0.9) of those with visual acuity 20/40 or better initially, a clinically meaningful but not statistically significant difference (P = 0.081). Results based on sensitivity analyses showed similar patterns. CONCLUSIONS: Both treatment groups demonstrated significant improvements in NEI-VFQ-25 scores; however, the improvement was immediate for the implant group as opposed to gradual for the systemic group. Poorer visual function was associated significantly with initial differences in NEI-VFQ-25 scores. However, only individuals in the implant group with poor visual acuity were able to overcome their initial deficits by the end of 3 years.

Asymptomatic Necrotizing Granulomatous Disease of the Neck With Unknown Etiology.

Patients presenting with unilateral neck masses is not an uncommon occurrence in an otolaryngology clinic. Especially those with risk factors such as older age and a history of smoking or drinking along with certain characteristics of the mass including rapid growth, immobility, and the presence of other masses elsewhere in the head and neck that can lead to more concerning etiologies such as cancer. However, in those who are younger with non-tender unilateral mobile masses, the differential is wide. We present the case of a 30-year-old male who presented with a non-tender left-sided neck mass with no associated or systemic symptoms. Workup including labs for HIV, syphilis, and fungal stains was negative. Pathology demonstrated lymphadenitis with necrotizing granulomas with no recurrence of symptoms after excisional biopsy. The patient continued to have no associated symptoms or recurrent mass thus no further workup was deemed necessary. Although unilateral neck mass and lymphadenitis with necrotizing lymphadenitis have a broad differential diagnosis, this patient's etiology continues to be unknown.

Base of Tongue Squamous Cell Carcinoma With Metastasis to the Mandibular Symphysis: A Case Report.

Squamous cell carcinoma (SCC) is the most common malignancy of the oropharynx (OP). Treatment of OP SCC includes chemotherapy, radiation, and/or surgery. OP SCC can spread via direct extension, lymphatics, or hematogenously. Although rare, distant metastases can occur in OP SCC. The most common sites of metastasis include the lungs, bone, and liver. Other less common sites include the skin, bone marrow, brain, kidneys, eyes, and heart. Patients who present with distant metastases usually have a poor prognosis. Sites of bone metastases from more common to less common include the spine, skull, ribs, and axial bones. In this article, we discuss a patient who presents with HPV+ base of tongue SCC with metastases to the lungs and mandible symphysis. Base of tongue SCC metastasizing to the mandible symphysis is a rarely reported location of metastasis.

Cowden Syndrome Case Report: Use of an Ultrasonic Surgical Aspirator for Cosmetic Removal of Lip Hamartomas.

Cowden syndrome (CS) is an autosomal dominant condition that is relatively rare. CS patients can have tumors derived from all three germlines. They can present with mucocutaneous hamartomas or other benign tumors, and have an increased risk of malignancies of the thyroid, breast, kidney, GI tract, and skin. In our clinic, a 40-year-old CS patient presented for thyroidectomy after fine needle aspiration was suspicious for papillary thyroid carcinoma (PTC). Another major concern was the cosmetic appearance of her lips, which were diffusely covered with small hamartomas. We were able to remove these in a novel manner using a cavitron ultrasonic surgical aspirator (CUSA; Integra Lifesciences, Princeton, NJ, USA). Using the CUSA tangential to the lip surface allowed for removal of the hamartomas in a way that created a smooth and cosmetically appealing outcome for the patient. The use of an ultrasonic surgical aspirator is a novel way to cosmetically treat hamartomas of the lip for CS patients.

Suprachoroidal CLS-TA for non-infectious uveitis: an open-label, safety trial (AZALEA).

PURPOSE: To evaluate local and systemic safety of suprachoroidal (SC) triamcinolone acetonide injectable suspension (CLS-TA) injections in subjects with non-infectious uveitis (NIU). DESIGN: Open-label, prospective multicentre safety study. PARTICIPANTS: Thirty-eight subjects with NIU, with and without macular oedema (MO). METHODS: Treatment consisted of two suprachoroidal injections of CLS-TA 4 mg, 12 weeks apart. Best-corrected visual acuity (BCVA), adverse event (AE) assessment, ophthalmic examinations and optical coherence tomography (OCT) were conducted every 4 weeks for 24 weeks. Blood samples were analysed for plasma triamcinolone acetonide (TA) concentrations. MAIN OUTCOME MEASURES: The main outcome measure was frequency of AEs. Other endpoints included plasma TA concentrations, change in signs of inflammation, BCVA and retinal central subfield thickness (CST). RESULTS: Based on a CST of >300 µm, 20 out of 38 subjects had MO at baseline. Mean intraocular pressure (IOP) was 13.3 mm Hg at baseline and 15.2 mm Hg at week 24 in the study eye. A total of six (15.8%) subjects had an IOP rise >10 mm Hg compared with baseline, in the study eye, and two (5.3%) subjects had IOP >30 mm Hg (maximum 34 mm Hg at week 8 and 38 mm Hg at week 20). Cataract formation AEs were reported in four study eyes; one of which was deemed treatment-related. No serious ocular AEs in the study eye occurred in the study. Quantifiable post-injection TA plasma concentration was <1 ng/mL. Efficacy parameters showed improvement over the 24-week study period. CONCLUSIONS: Suprachoroidally administered CLS-TA was safe and well tolerated over the 24-week, open-label study in NIU subjects with and without MO.

Extension study of the safety and efficacy of CLS-TA for treatment of macular oedema associated with non-infectious uveitis (MAGNOLIA).

PURPOSE: To assess the extended efficacy and safety of suprachoroidal triamcinolone acetonide injectable suspension (CLS-TA) among patients with macular oedema (ME) secondary to non-infectious uveitis (NIU). METHODS: Patients with uveitic ME were treated with suprachoroidal CLS-TA at baseline and week 12 of the Efficacy and Safety of Suprachoroidal CLS-TA for Macular Edema Secondary to Noninfectious Uveitis: Phase 3 Randomized Trial (PEACHTREE) study. Time to rescue was evaluated over 24 additional weeks for MAGNOLIA. Safety data, visual acuity and retinal central subfield thickness (CST) reduction were also evaluated. Of the 53 eligible patients (46 CLS-TA and 7 control), 33 patients were enrolled (28 CLS-TA and 5 control). RESULTS: Over the entire 48-week period for PEACHTREE and MAGNOLIA, the median time to rescue therapy was 257 days versus 55.5 days for the CLS-TA and sham-control arms, respectively. Of 28 CLS-TA treated patients who participated in MAGNOLIA, 14 (50%) did not require rescue therapy through approximately 9 months after the second treatment. Among CLS-TA patients not requiring rescue, there was a mean gain of 12.1 letters and mean CST reduction of 174.5 µm at week 48. No serious adverse events related to study treatment were observed. CONCLUSION: Approximately 50% of patients did not require additional treatment for up to 9 months following the last CLS-TA administration.

High-risk human papillomavirus (HPV) screening and detection in healthy patient saliva samples: a pilot study.

BACKGROUND: The human papillomaviruses (HPV) are a large family of non-enveloped DNA viruses, mainly associated with cervical cancers. Recent epidemiologic evidence has suggested that HPV may be an independent risk factor for oropharyngeal cancers. Evidence now suggests HPV may modulate the malignancy process in some tobacco- and alcohol-induced oropharynx tumors, but might also be the primary oncogenic factor for inducing carcinogenesis among some non-smokers. More evidence, however, is needed regarding oral HPV prevalence among healthy adults to estimate risk. The goal of this study was to perform an HPV screening of normal healthy adults to assess oral HPV prevalence. METHODS: Healthy adult patients at a US dental school were selected to participate in this pilot study. DNA was isolated from saliva samples and screened for high-risk HPV strains HPV16 and HPV18 and further processed using qPCR for quantification and to confirm analytical sensitivity and specificity. RESULTS: Chi-square analysis revealed the patient sample was representative of the general clinic population with respect to gender, race and age (p < 0.05). Four patient samples were found to harbor HPV16 DNA, representing 2.6% of the total (n = 151). Three of the four HPV16-positive samples were from patients under 65 years of age and all four were female and Hispanic (non-White). No samples tested positive for HPV18. CONCLUSIONS: The successful recruitment and screening of healthy adult patients revealed HPV16, but not HPV18, was present in a small subset. These results provide new information about oral HPV status, which may help to contextualize results from other studies that demonstrate oral cancer rates have risen in the US among both females and minorities and in some geographic areas that are not solely explained by rates of tobacco and alcohol use. The results of this study may be of significant value to further our understanding of oral health and disease risk, as well as to help design future studies exploring the role of other factors that influence oral HPV exposure, as well as the short- and long-term consequences of oral HPV infection.

Transoral robotic submandibular gland transposition to reconstruct radical tonsillar resection defects.

Significant dysphagia, pain, and risk of bleeding occur after transoral robotic surgery (TORS) radical tonsillectomy. We present a novel surgical technique utilizing robotically assisted submandibular gland transposition (SMGT) to reconstruct the radical tonsillar defect. A 48-year-old male with p16+ tonsillar squamous cell carcinoma underwent deep TORS radical tonsillectomy, contralateral tonsillectomy, ipsilateral neck dissection, and TORS-assisted reconstruction of the radical defect with ipsilateral SMGT. Postoperatively, the patient experienced minimal pain and was discharged on postoperative day (POD) 3 tolerating a soft diet. There were no episodes of postoperative bleeding. This procedure was performed in five other cases as well. Transoral robotic SMGT can be used successfully to repair deep TORS radical tonsillectomy defects and may theoretically reduce dysphagia, pain, and the risk of hemorrhage.

Management of traumatic laryngotracheal separation: Case series and review.

Laryngotracheal separation injuries are a rare but serious condition, as survival from such injuries relies on proper airway management. As a result, recommendations for management have been based on small case reports and expert opinion. We reviewed our last 10 years of experience with managing laryngotracheal separation injuries and identified 6 cases for chart review. Awake tracheostomy or videolaryngobronchoscopy was used in each case to initially obtain the airway. Surgical repair was then performed immediately using nonabsorbable monofilament suture or a miniplate, and a low fenestrated tracheostomy was placed. All of our patients who followed up were decannulated, eating regular diets, and had satisfactory voice quality at 3 months postoperatively. Review of the literature revealed that, while management strategies have changed over time, treatment still varies widely depending on surgeon preference and the details of each injury. Outcomes from our series suggest that our described techniques and management strategies can be used with good outcomes. We believe that this is due to securing a safe airway, early surgical intervention with no unnecessary tissue dissection, effective reconstruction of the airway, and the fenestrated tracheostomy technique.

Management of repository corticotropin injection therapy for non-infectious uveitis: a Delphi study.

PURPOSE: Diagnosis and management of non-infectious uveitis (NIU), a major cause of blindness worldwide, are challenging. Corticosteroids, the cornerstone of therapy, are not appropriate for long-term use, and while non-biologic and biologic immunomodulators may be used for some patients, data on their efficacy and safety in this population are limited. Repository corticotropin injection (RCI), believed to affect uveitis by multiple mechanisms, has received regulatory approval for treatment of ophthalmic diseases including posterior uveitis, but is not widely used or discussed in guidelines for the management of uveitis and ocular inflammatory diseases. METHODS: The index study employed a modified Delphi process with a panel of 14 US-based ophthalmologists. Consensus recommendations were developed through a series of three questionnaires. Panellists rated statements on a Likert scale from -5 (strongly disagree) to +5 (strongly agree). RESULTS: The Delphi panel provided consensus recommendations on examinations and testing needed for diagnosis, treatment goals, and the use of corticosteroids, as well as the use of non-biologic and biologic immunomodulators. The panel reached consensus that RCI may be considered for posterior and pan-uveitis, and dosing should be individualized for each patient. Dose reduction/discontinuation should be considered for excessive RCI-related toxicity, hyperglycaemia and/or diabetic complications, excessive costs, or remission ≥ 2 years. Patients should be weaned from RCI if uveitis is stable and well controlled. Adverse events during RCI therapy can be managed by appropriate interventions, with dose reduction/discontinuation considered if events are severe or recurrent. CONCLUSIONS: Expert consensus suggests RCI may be an appropriate treatment option for some patients with uveitis when other therapies are ineffective or intolerable.

Distal facial nerve exposure: a key to partial parotidectomy.

OBJECTIVES: 1) Compare outcomes of distal facial nerve identification with antegrade exposure in partial parotidectomy; 2) Be able to incorporate other modifications of parotidectomy including preservation of the great auricular nerve, superficial musculo-aponeurotic system (SMAS), and parotid duct. STUDY DESIGN: Case series with chart review of partial parotidectomy for benign neoplasms and intraparotid lymph nodes, using antegrade (Group 1) or distal (Group 2) facial nerve exposure, and those conserving the great auricular nerve, SMAS, and parotid duct (Group 3). SUBJECTS AND METHODS: Outcomes for the three groups were reviewed. The great auricular nerve, parotid duct, and SMAS were preserved when possible. Outcomes examined included postoperative facial nerve function, earlobe sensation, allograft use for SMAS defects, surgical duration, sialocele, or salivary fistula. RESULTS: No difference in facial nerve function was found between the groups. Group 3 had better ear lobule cutaneous sensation. No sialoceles occurred in the 10 of 14 Group 3 cases in which parotid ducts were preserved. CONCLUSIONS: Partial parotidectomy utilizing distal facial nerve exposure can reduce the extent of surgical dissection, facilitate preservation of the parotid duct and great auricular nerve, and allow greater flexibility in the choice of skin and SMAS incisions.

Implementation of submandibular gland transfer: A multi-institutional study of feasibility and time to treatment.

BACKGROUND: Submandibular gland transfer (SMGT) mitigates radiation-induced xerostomia but has yet to be widely adopted. We evaluate the feasibility of incorporating SMGT at multiple academic institutions and report the incidence of treatment delay. METHODS: Forty-nine patients were identified who underwent SMGT. Time points pertaining to diagnosis and key treatment events including SMGT, surgery, chemotherapy, and radiation were extracted. Treatment delay was defined as either >60 days from diagnosis to definitive therapy or >6 weeks between surgery and adjuvant therapy. RESULTS: Median time from diagnosis to primary treatment was 42 days (IQR, 32-54). Median time from surgery to adjuvant therapy was 33 days (IQR, 28-47). Delay in starting treatment was observed in 7/49 patients (14%). Six patients incurred a delay in postoperative radiation therapy (6/19; 32%). CONCLUSIONS: With appropriate care coordination, SMGT can be implemented into a clinical pathway with a goal of decreasing radiation-induced xerostomia without increasing treatment delays.

Rate of Retinal Detachment after Early Prophylactic Vitrectomy for Acute Retinal Necrosis.

PURPOSE: To compare the rate of retinal detachment after acute retinal necrosis in eyes that underwent early vitrectomy versus no early vitrectomy. METHODS: Charts of patients (61 eyes) who presented to Texas Retina Associates between January 1, 2006 and December 30, 2014 for acute retinal necrosis were reviewed. Charts with incomplete documentation or follow-up less than 6 months were excluded. Twenty-nine remaining eyes were divided into two groups: early vitrectomy and no early vitrectomy. Primary outcome measure was rate of retinal detachment. RESULTS: Out of 29 eyes, 12 underwent early vitrectomy within 30 days of diagnosis and 17 either underwent vitrectomy after 30 days or did not undergo prophylactic vitrectomy at all. Three out of 12 eyes (25%) developed retinal detachment in the early vitrectomy group versus 10 out of 17 eyes (59%) in the no early vitrectomy group (p = 0.076). CONCLUSIONS: Early vitrectomy within 30 days may prevent retinal detachment after acute retinal necrosis.

Study of the upper airway of obstructive sleep apnea patient using fluid structure interaction.

Up to 14% of the U.S. population is estimated to have obstructive sleep apnea (OSA), while the outcomes of the treatments have variable results. In the current study, a three-dimensional fluid-structure interaction modeling was applied to simulate the upper airway to identify the precise location, severity, and characteristic of airway collapse. This was accomplished using Simpleware® and ANSYS® software applied to a 3-D rendering of the airway in a real patient with severe OSA. During this simulation, areas which are prone to collapse and precipitate apneic episodes were identified at the tip of the soft palate and the base of the tongue, with intrathoracic pressure as low as -1370 Pa. These results are consistent with anatomical structures currently indicated and targeted in the treatment of OSA. This improved FSI modeling simulation, which is the first to completely model the whole upper airway without consideration of the nasal cavity in OSA, and can allow virtual modification of the airway prior to actual treatment by doctors.

The Plication Technique to Enhance the Endoscopic Approach to Zenker's Diverticulum.

Endoscopic stapler approaches to Zenker's diverticulum often yield a persistent diverticulum and recurrent dysphagia up to 20%. A novel technique to reduce the postoperative diverticulum is described. Eight consecutive patients with Zenker's diverticulum who underwent endoscopic stapler diverticulotomy had adjunctive endoscopic plication of the diverticulum wall to functionally reduce the residual diverticulum size. On postoperative esophagram, there was no visible diverticulum in 4 of 7 patients (57%). The remaining 3 patients had a reduction in common wall of 76%, 50%, and 40% with a mean postoperative size of 1.0 cm. All patients had resolution or significant improvement in dysphagia. There were no complications or recurrences at a mean follow-up of 6.3 months. As an adjunct to endoscopic treatment of Zenker's diverticulum, the plication technique can reduce diverticulum size. Further studies will determine if the plication technique affects long-term recurrence of endoscopic stapler approaches.

Perillyl alcohol and perillic acid induced cell cycle arrest and apoptosis in non small cell lung cancer cells.

Plant products such as perillyl alcohol have been reported to possess anti-tumor activities against a number of human cancers though the mechanism of action has not yet been elucidated. The effects of perillyl alcohol (POH) and its metabolite perillic acid (PA) on the proliferation of non small cell lung cancer (NSCLC, A549, and H520) cells were investigated. Both POH and PA elicited dose-dependent cytotoxicity, induced cell cycle arrest and apoptosis with increasing expression of bax, p21 and caspase-3 activity in both the cell lines. Combination studies revealed that exposing the cells to an IC50 concentration of POH or PA sensitized the cells to cisplatin and radiation in a dose-dependent manner. These results indicate that POH and PA in combination therapy may have chemotherapeutic value against NSCLC.

Methyl jasmonate induced apoptosis in human prostate carcinoma cells via 5-lipoxygenase dependent pathway.

Methyl jasmonate--a plant stress hormone with striking resemblance to lipoxygenase products have been reported to induce apoptosis in several cancers. However, 5-HETE--a product of the lipoxygenase pathway has been implicated in human prostate cancer progression and yet possible interaction between methyl jasmonate and the lipoxygenase pathway has not been reported, thus, leaving some unanswered questions on the mechanism(s) of action by methyl jasmonate. Using cytotoxicity and flow cytometry assays (BrdU assay) as well as fluorescence microscopy, we investigated the effects of the methyl jasmonate on the proliferation of human prostate adenocarcinoma cell lines (DU-145, PC-3) in vitro and the potential interaction between methyl jasmonate and the lipoxygenase pathway. Methyl jasmonate (MJ) significantly (p = 0.01) inhibited the proliferation of human prostate carcinoma cells in dose- and kinetic-dependent manners and showed specific interaction with 5-lipoxygenase (5-LOX) enzyme pathway. Flow cytometric analyses and fluorescence microscopy confirmed that the inhibition of proliferation was via the induction of apoptosis. Based on our findings, it can be proposed that the interaction of methyl jasmonate with 5-lipoxygenase pathway may participate in the observed anticarcinogenic property.