Non-malignant Growth Research Articles

Evaluation of intralesional 5-fluorouracil versus intralesional interferon alpha in treatment of warts

Background: Warts are non-malignant growth of the skin and mucous membranes resulting from infection with human papillomavirus (HPV). It can significantly impact the quality of life for patients and elicit feeling of embarrassment. Aim and objectives: A comparative analysis of the efficacy of intralesional 5-FU and intralesional interferon alpha among distinct groups of patients diagnosed with warts. Patients and methods: This is a cohort of sixty individuals diagnosed with warts were selected from the period of early April 2022 to the end of April 2023. Results: There was a statistically significant difference (P-value=0.005) seen between the two groups, namely group A and group B, in relation to the final response. In group A (5-Fluorouracil)), complete clearance was achieved by 23 patients (76.7%), with 7 patients (23.3%) showing partial response. No instances of resistance were observed in this group. Conversely, in group B (Interferon alpha), only 11 patients (36.7%) attained complete clearance, while 16 patients (53.3%) exhibited partial response, and resistance was evident in 3 cases (10%). Conclusion: Intralesional 5-Fluorouracil (5-FU) is highly effective, cheaper, and easily available in treating warts. The combination of the both treatments may deliver a greater benefit to patients with resistant warts.

THU015 Unilateral Adrenal Hyperplasia Causing ACTH-independent Hypercortisolism

Abstract Disclosure: N. Mogar: None. M.A. McConnell : None. R. Yu: None. J.E. Weinreb: None. Background: Adrenal cortical hyperplasia is defined radiographically as a non-malignant growth or enlargement of the adrenal glands. Adrenal hyperplasia is most commonly bilateral, with unilateral adrenal hyperplasia occurring less frequently. Unilateral adrenal hyperplasia has been associated with primary hyperaldosteronism, and there are only a few case reports describing unilateral adrenal hyperplasia associated with ACTH-independent hypercortisolism. Clinical Case: A 56-year-old man with sleep apnea was incidentally found to have a 4.6 cm left adrenal nodule found on computed tomography (CT) chest imaging. Adrenal CT revealed a heterogeneous 4.6 x 3.3 x3.7 cm left adrenal mass with internal calcifications and a portion of the mass measuring 38 Houndsfield units (HU). His 8AM serum cortisol level was 19.80 mcg/dL (5-23 mcg/dL). No ACTH level was collected; however, a serum DHEA-S level was 55 mcg/dL (32-240 mcg/dL). After low dose dexamethasone suppression test (LDDS), the serum cortisol level was elevated at 2.3 mcg/dL (<1.8 mcg/dL). Repeat LDDS revealed a cortisol level of 2.9 mcg/dL. A 24-hour urine free cortisol level was 27.2 mcg/24h (4-50 mcg/24h). Testing for pheochromocytoma and hyperaldosteronism was negative. The patient had no historical or physical signs of Cushing’s syndrome and no signs of malignancy. Due to concerning features on adrenal CT imaging (tumor size >4 cm, internal calcifications, and HU >10), the patient underwent unilateral adrenalectomy. The patient did not receive intraoperative corticosteroids and remained normotensive post-operatively. However, his post-operative 8AM cortisol level was <0.2 mcg/dL (5-23 mcg/dL) on two separate occasions. He was discharged on a short course of hydrocortisone, with eventual recovery of his hypothalamic-pituitary-adrenal (HPA) axis. Pathology revealed a diagnosis of cortical adrenal hyperplasia. Conclusion: The presence of postoperative hypocortisolemia demonstrates that this patient had ACTH-independent hypercortisolism. This case report would be one of few describing the rare diagnosis of unilateral adrenal hyperplasia associated with ACTH-independent hypercortisolism and would add to the sparse literature currently available on this condition. Additionally, this case report highlights the clinical significance of mild autonomous cortisol secretion (MACS); despite only having an unsuppressed cortisol level following LDDS, this patient was found to have a suppressed HPA axis after unilateral adrenalectomy requiring corticosteroids. Early identification and treatment of MACS and treatment of adrenal insufficiency following adrenalectomy is essential to prevent adverse events. Presentation: Thursday, June 15, 2023

Preferred methods of Diagnosis and Treatment of Benign Prostatic Hyperplasia adopted by Ayurveda practitioners - A Survey Study

Introduction: Benign Prostatic Hyperplasia (BPH) refers to the nonmalignant growth of prostate gland. In Ayurveda, it can be correlated with Mutraaghata or Mutradosha. Currently used common oral medications such as 5α-reductase inhibitors, α1-Blockers as well as surgical treatment methods such as Transurethral Resection of the Prostate (TURP) have well-known side effects. Ayurveda case studies on BPH show evidence of a potential alternative to these current methods. Objectives: To conduct a survey to know the diagnostic methods and treatment modalities used by different Ayurveda Practitioners in BPH treatment. Materials & Methods: A survey comprising 7 questions in the form of multiple-choice questions on the diagnosis and treatment methods of BPH adopted by Ayurveda Physicians was done. The answers were recorded and interpreted in the form of graphs and pie charts. Results: A total of 57 different Ayurveda practitioners participated in the survey. Prevalence of BPH was seen more in the age group of 60-70 years. Ultrasonography (USG) and Prostate Specific Antigen (PSA) were among the most commonly used diagnostic methods for BPH. Most common symptoms observed were increased frequency of urine, urine incontinence and urine urgency. Uttara Basti (administration of medicine through the urethra) was the most recommended type of treatment procedure preferred, followed by Matra Basti (enema). Avagaha Swedana (Sitz bath) was recommended by most practitioners. The course duration of treatment is advised to be around half to one month. Around 40-60% relief was claimed in patients with BPH by the participants. Conclusion: BPH is a condition that is currently being treated by various Ayurveda practitioners using classical treatment methods such as Uttara Basti, Matra Basti etc. with claimed relief of about 40-60% by the participants.

Recent Updates in Surgical Treatment of Benign Prostatic Hyperplasia: A Review Article

Benign prostatic hyperplasia refers to the non-malignant growth or enlargement of the prostate gland and is a general cause of lower urinary tract symptoms in men which rises with growing age. There is a wide range of management options available from watchful waiting, and medicinal therapy to various surgical intervention methods. Though medicinal therapy is the preliminary treatment for benign prostatic hyperplasia, some patients lack the desire to keep on with the extended duration, and on occasion, they must break either due to treatment failure or side effects. Lately, numerous innovative surgical methodologies have been established to provide patients with efficient therapy on a day-care basis, without the risk of general anaesthesia and with rapid recovery, marginal morbidity, and safeguarding the reproductive function. Existing treatment alternatives for benign prostatic hyperplasia differ in the extent of intrusiveness, efficiency, complications, and cost-effectiveness. Various treatment modalities are available these days that are less invasive and have lesser complications as compared to conventional transurethral resection of the prostate. It helps curtail expenses, preserve time for recovery, curb untoward general and reproductive side effects. Laser, endoscopic, robotic, water vapor utilization, and various other minimally invasive methods have demonstrated their effectiveness in the treatment of benign prostatic hyperplasia in various studies.

Development and optimization of a tamsulosin nanostructured lipid carrier loaded with saw palmetto oil and pumpkin seed oil for treatment of benign prostatic hyperplasia

Benign prostatic hyperplasia (BPH) is a nonmalignant growth of the prostate tissue and causes urinary tract symptoms. To provide effective treatment, tamsulosin (TM), saw palmetto oil (SP), and pumpkin seed oil (PSO) were combined and fabricated a nanostructured lipid carrier (NLC) as TM-S/P-NLC using experimental design. The purpose was to enhance the permeation and therapeutic activity of TM; combining TM with SP and PSO in an NLC generates a synergistic activity. An optimized TM-S/P-NLC was obtained after statistical analysis, and it had a particle size, percentage of entrapment efficiency, and steady-state flux of 102 nm, 65%, and 4.5 μg/cm2.min, respectively. Additionally, the optimized TM-S/P-NLC had spherical particles with a more or less uniform size and a stability score of 95%, indicating a high level of stability. The in vitro release studies exhibited the optimized TM-S/P-NLC had the maximum release profile for TM (81 ± 4%) as compared to the TM-NLCs prepared without the addition of S/P oil (59 ± 3%) or the TM aqueous suspension (30 ± 5%). The plasma TM concentration–time profile for the TM-S/P-NLC and the marketed TM tablets indicated that when TM was supplied in a TM-S/P-NLC, the pharmacokinetic profile of the drug was improved. Simultaneously, in vivo therapeutic efficacy studies also showed favorable results for the TM-S/P-NLC in terms of the prostate weight and prostate index following treatment of BPH. Based on the findings of present study, we suggest that in the future, the TM-S/P-NLC could be a novel drug delivery system for treating BPH.

Establishment and Characterization of Brain Cancer Primary Cell Cultures From Patients to Enable Phenotypic Screening for New Drugs

Aim: Desmoplastic infantile ganglioglioma (DIG), is a rare tumor arising mainly during the first 2 years of life. Molecular characterization of these benign yet rapidly proliferating tumors has been limited to evaluating a few mutations in few genes. Our aim was to establish a live cell culture to enable the understanding of the cellular processes driving the non-malignant growth of these tumors. Methods: Tumor tissue from a rare non-infantile 8-year-old female DIG patient was dissociated and digested using collagenase to establish live cultures. Both 2D monolayer and 3D neurospheres were successfully cultured and characterized for proliferative potential, intrinsic plasticity, presence of cancer stem cells and the expression of stem cell markers. Cells cultured as 3D were embedded as tissue blocks. Immunohistochemistry was performed in both tissue and 3D sections for markers including synaptophysin, vimentin, neurofilament and MIB-1. Mutation analysis by NGS was performed using a-100 gene panel. Results: Using immunohistochemistry, the 3D cultures were shown to express markers as in the original DIG tumor tissue indicating that the spheroid cultures were able to maintain the heterogeneity found in the original tumor. Cells continued proliferating past passage 10 indicative of immortalization. Enrichment of cancer stem cells was observed in neurospheres by FACS using CD133 antibody and RT-PCR. Mutation analysis indicated the presence of germline mutations in three genes and somatic mutations in two other genes. Conclusion: A spontaneous cell line-like cell culture with high percentage of stem cells has been established from a DIG tumor for the first time.

Huge median prostatic lobe: a interesting case of BPH

Benign Prostatic Hyperplasia (BPH) refers to the nonmalignant growth or hyperplasia of prostate tissue and is a common cause of lower urinary tract symptoms in men [1].

Surgical management of oral submucous fibrosis with promising use of nasolabial flap

Purpose: To evaluate the efficacy of nasolabial (NL) flap as a grafting technique in the management of oral submucous fibrosis (OSMF).Patients and Methods: A prospective randomized study was conducted including 10 patients who were treated surgically for OSMF. Patients with the chief complaint of long standing difficulty in mouth opening (less than 20mm), pain in relation with the third molars or any non-malignant growth associated with that region were included.Results: This prospective study was carried out to evaluate the use of NL flap as a grafting technique in OSMF cases and observe the surgical outcome in terms of post-surgical mouth opening.1 week post- operative mouth opening ranged from 25mm to 45mm with a mean of 36 mm. However, 15 days, 1 month and 3 months post-operative mouth opening was 32, 34, and 36 mm respectively. Finally the 12 months follow up showed a range from 22 mm to 44 mm with a mean of 34 mm.Conclusion: Cessation of habits, vigorous mouth opening exercises and improvement in nutritional statusis must for better results post-operatively. All the patients showed sustained mouth opening, satisfactory epithelialization, and minimum wound contracture. The NL flap has proven to be a useful and reliable treatment modality.

Crocin treatment improves testosterone induced benign prostatic hyperplasia in rats

Background and objective: Benign prostatic hyperplasia (BPH) is a typical nonmalignant growth of the prostate in the elderly. Crocin, a bioactive component of Crocus sativus L., commonly known as saffron, is known to have an anti-proliferative activity against numerous types of cancer, including prostate cancer. This study investigated the effects of crocin on testosterone-induced BPH development in rats. Materials and methods: The study sample included three groups of adult male rats (3 months old, weighed 250 g): the control group received corn oil only, the second and the third groups were injected with testosterone (3 mg/kg dissolved in corn oil) subcutaneously. The second group was considered as testosterone-induced BPH (untreated) while the third groups were assigned as testosterone-induced BPH-crocin treated group (100 mg/kg orally for 14 days). Results: After animal sacrifice, histopathological analysis of the prostate tissues was performed in parallel with gene expression of proliferation (PCNA), inflammation (IL-6), and vascularization (VEGF-A) markers, analyzed by qRT-PCR. Crocin treatment significantly reduced prostate index and the thickness of the epithelial layer in rats with BPH. Additionally, the mRNA expression levels of PCNA, a marker of cell proliferation; IL-6, an inflammatory cytokine; and VEGF-A, an angiogenesis marker, were significantly down-regulated in the BPH group that were treated with crocin. Conclusions: The present study indicates that crocin can effectively prevent the development of experimentally induced BPH through inhibition of prostatic cellular proliferation, inflammation, and angiogenesis.

The Influencing Role of Diabetes Mellitus and Hypertension in the Establishment of Benign Prostatic Hyperplasia

Background: Benign prostatic hyperplasia is regarded as non-malignant growth of prostatic tissueIt is the most common benign tumor in men, and the incidence is age related. In men aged more than 50 years, it is the fourth most prevalent disease. This study aim to determine the association of benign prostatic hyperplasia with diabetes mellitus and/or hypertension and this may help to bring out new dimensions in management of benign prostatic hyperplasia, hypertension and diabetes mellitus.
 Materials and Methods: Five hundred forty patients, diagnosed as benign enlargement of prostate with control group 270 at Urology out patient door between May 2018 to February 2019 with approval of Institutional review committee, were included. Patient with history of prostate cancer, neurogenic bladder, those who had undergone surgical intervention for prostate, not willing to take part in study were excluded.
 Results: Age range in cases and control were from 41–94 years. Diabetes was present in 14.63% of cases and 11.85% of controls. The positive association was established between prostatic hyperplasia and Diabetes (P-0.27). Hypertension was present in 37.96% of cases and 29.63% of controls (P-0.019). Diabetes and Hypertension were present in 56.48% in cases and 43.33% in control (P-0.000).
 Conclusion: Study suggests that benign prostatic hyperplasia is associated with diabetes mellitus and hypertension and may help to bring out new dimensions in management of benign prostatic hyperplasia.

6-sialyllactose ameliorates dihydrotestosterone-induced benign prostatic hyperplasia through suppressing VEGF-mediated angiogenesis

Benign prostatic hyperplasia (BPH), a common disease in elderly males, is accompanied by non-malignant growth of prostate tissues, subsequently causing hypoxia and angiogenesis. Although VEGF-related angiogenesis is one of the therapeutic targets of prostate cancer, there is no previous study targeting angiogenesis for treatment of BPH. Dihydrotestosterone (DHT)-induced expressions of vascular endothelial growth factor (VEGF) in prostate epithelial RWPE-1 cells and human umbilical vascular endothelial cells (HUVECs). Conditioned media (CM) from DHT-treated RWPE-1 cells were transferred to HUVECs. Then, 6SL inhibited proliferation, VEGFR-2 activation, and tube formation of HUVECs transferred with CM from DHT-treated RWPE-1 cells. In the rat BPH model, 6SL reduced prostate weight, size, and thickness of the prostate tissue. Formation of vessels in prostatic tissues were also reduced with 6SL treatment. We found that 6SL has an ameliorative effect on in vitro and in vivo the BPH model via inhibition of VEGFR-2 activation and subsequent angiogenesis. These results suggest that 6SL might be a candidate for development of novel BPH drugs.

Adrenal cortical hyperplasia: diagnostic workup, subtypes, imaging features and mimics

Adrenal cortical hyperplasia manifests radiologically as a non-malignant growth, or enlargement, of the adrenal glands, specifically the cortex, although the cortex cannot be definitively identified by conventional imaging. Controlled by the pituitary gland, the adrenal cortex drives critical processes, such as the production of cortisol, mineralocorticoid and sex hormones. Any disruption in the multiple enzymes and hormones involved in these pathways may cause serious or life-threatening symptoms, often associated with anatomical changes in the adrenal glands. Diagnosis and treatment of adrenal cortical hyperplasia requires a thorough clinical evaluation. As imaging has become more robust so has its role in the diagnosis and treatment of adrenal conditions. CT has been the primary modality for adrenal imaging owing to reproducibility, temporal and spatial resolution and broad access. MRI serves a complimentary role in adrenal imaging and can be used to further evaluate indeterminate CT findings or serve as an adjunct tool without the use of ionizing radiation. Ultrasound and fluoroscopy (genitography) are most commonly used in children and foetuses to evaluate congenital adrenal hyperplasia. This article will discuss the clinical presentation, laboratory workup and imaging features of adrenal cortical hyperplasia, both congenital and acquired.

Bilateral buccal exostosis evaluated by cone-beam computed tomography: A rare accidental finding

Buccal exostoses are broad-based, non-malignant surface growth occurring on the outer or facial surface of the maxilla and/or mandible, found usually in the premolar and molar region. Etiology is still not established, but it has been suggested that the bony overgrowth can be because of abnormally increased masticatory forces to the teeth. Compensatory response to periodontal disease has been proposed to explain some cases of exostoses; they tend to appear in early adolescence and may very slowly increase in size with time. They are painless, self-limiting and may increase patient concern about poor esthetics, inability to perform oral hygiene procedures, and compromised periodontal health by causing food lodgment. The following article presents a very rare case of bilateral buccal-sided maxillary and mandibular exostoses in the anterior region which was an accidental finding in a chronic generalized periodontitis patient.

Niacin esters of chalcones with tumor-selective properties

Novel series of niacin esters of chalcones 2, 4 and 6 were designed as antineoplastic agents that have the potential to release the chemoprotectant niacin. These enones are cytotoxic to human CD4+ T-lymphocyte Molt 4/C8 and CEM and murine leukemia L1210 cells. Quantitative structure–activity relationship (QSAR) studies of the biodata in series 4 revealed that cytotoxic potency was enhanced by placing electron-repelling groups in one of the aryl rings. The compounds are lethal to HL-60, HSC-2, HSC-3 and HSC-4 neoplasms but less toxic to nonmalignant hepatocyte growth factor, hematopoietic progenitor cell and human periodontal ligament fibroblast cells. Hence, the compounds display tumor-selective toxicity. These chalcones are well tolerated in mice and no overt toxicity was noted. The results establish that in general the compounds in series 2, 4 and 6 have positive characteristics which warrant further studies.

Diffuse Extensive Esophageal Papillomatosis: A Rare Cause of Dysphagia

Esophageal squamous papilloma is a benign epithelial tumor, usually seen as a solitary, small, white or pink, sessile or polypoid mass. The true incidence of esophageal papillomatosis is unknown, however, various studies estimate the incidence between 0.007-0.43%1. Fifteen percent of papillomatosis cases are seen as multiple lesions and even fewer are extensive disease2. We present a case of diffuse extensive papillomatosis. A 69 year old African-American gentleman with hypertension, COPD and alcohol abuse who presented with 2-3 months of dysphagia, and 40 pounds of weight loss over 10 months. Esophagogastroduodenoscopy (EGD) revealed a partially circumferential/obstructing friable necrotic appearing mass in the mid-esophagus which was biopsied. Distal to the large mass were small, circumferential, pearly, wart/finger-like exophytic growths which spared the very distal esophagus and the gastroesophageal junction. PET/CT scan revealed circumferential thickening and a hypermetabolic mid-esophageal wall over a length of 10cm, concerning for a primary esophageal cancer without evidence of metastatic disease. Initial pathology revealed no evidence of malignancy. The patient underwent two additional flexible EGDs with biopsies which were unrevealing. The patient finally underwent rigid esophagoscopy with biopsy with pathology revealing squamous papillomas. This was confirmed with pathology from a repeat EGD showing squamous papillomas without any evidence of malignancy. Our case is unique given the rarity of diffuse esophageal papillomatosis and highlights the challenges in diagnosing extensive disease as a non-malignant growth. Of note, 30 % of all lesions are associated with HPV and currently HPV on our patient remains pending. [1]. Syrjänen et al. Detection of human papillomavirus in esophageal papillomas: systematic review and meta-analysis. APMIS. 2013 May;121(5):363-74. [2]. Odze et al. Esophageal squamous papillomas. A clinicopathologic study of 38 lesions and analysis for human papillomavirus by the polymerase chain reaction. Am J Surg Pathol.1993 Aug;17(8):803-12.Figure 1Figure 2

Characterization of ductal carcinoma in situ cell lines established from breast tumor of a Singapore Chinese patient.

BackgroundFive cell lines were established from a Singaporean patient of Chinese origin with breast ductal carcinoma in situ (DCIS). These five cell lines express exogenous human telomerase reverse transcriptase (hTERT) which confers the ability to proliferate indefinitely.MethodsCells were isolated from the DCIS excision and transfected with a plasmid expressing hTERT, a catalytic subunit of telomerase. Five immortalized colonies were propagated and characterized by karyotyping, array comparative genomic hybridization (CGH), immunostaining and Western blots for biomarkers, in vitro anchorage independent growth, in vivo mouse tumorigenicity, drug sensitivity, species authentication and virology safety testing.ResultsArray CGH analysis showed that the cell lines harbored different specific genetic aberrations. Common mutations observed in most breast cancer cell lines such as the general loss of heterozygosity (LOH) throughout chromosome X and chromosome 17 are also observed in our cell lines. The cell lines were further characterized as human breast cells that are estrogen- and progesterone-receptor positive, and sensitive to tamoxifen. The cell lines showed anchorage-independent growth in the soft agar assay and can grow in common culture medium without supplementation with growth factor, therefore demonstrating transformed characteristics. Four of the cell lines can engraft and form measureable tumors after 50 days when injected subcutaneously into immune-deficient (SCID) mice. The weak tumorigenicity of these cell lines corresponded well with their non-malignant growth origin. The cell lines were authenticated to be of human origin based on DNA fingerprint of the cells. The cell lines were free from contamination of 20 viruses and mycoplasma in the virological safety test panel.ConclusionsUnlike most available breast cell lines, our cell lines are derived from primary breast cancer tissues that represent earlier grades or tumor progression stages. They would be useful as study models for basic and clinical research programs directed at early diagnosis and intervention.

Linking Pre-Diabetes with Benign Prostate Hyperplasia. IGFBP-3: A Conductor of Benign Prostate Hyperplasia Development Orchestra?

Benign prostatic hyperplasia (BPH) represents a pattern of non-malignant growth of prostatic fibromuscular stroma. Metabolic disturbances such us pre-diabetes and metabolic syndrome may have a role in BPH pathophysiology. A potential explanation for the above relationship involves the insulin-like growth factor (IGF) axis as well as IGF binding proteins, (IGFBPs) of which the most abundant form is IGFBP-3. Therefore, the aim of the present study was to investigate the association between intra-prostatic levels of IGF-1, IGF-2 as well as to evaluate the role of locally expressed IGFBP-3 in BPH development in pre-diabetes. A total of 49 patients admitted to the Urology department of a tertiary urban Greek hospital, for transurethral prostate resection, or prostatectomy and with pre-diabetes [impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) or both] were finally included. The majority of the sample consisted of subjects with IGT (51.0%), followed by IFG and IGT (32.7%) and isolated IFG (16.3%). For all participants a clinical examination was performed and blood samples were collected. In addition, total prostate (TP) volume or transitional zone (TZ) volume were estimated by transrectal ultrasonography. The results of the multivariate analysis regarding TP volume showed that higher PSA (p<0.001), larger waist circumference (p=0.007) and higher IGFBP-3 expression levels (p<0.001) independently predicted higher TP volume. The results regarding the volume of the TZ showed that higher PSA (p<0.001), larger waist circumference (p<0.001) and higher IGFBP-3 expression levels (p=0.024) were independently associated with higher TZ volume. Our findings show that intra-prostatic levels of IGFBP-3, PSA and waist circumference, but not overall obesity, are positively associated with prostate volume. IGFBP-3 seems to be a multifunctional protein, which can potentiate or inhibit IGF activity.

Novel insights into the role of the tumor suppressor von Hippel Lindau in cellular differentiation, ciliary biology, and cyst repression

The growth and differentiation of renal tubular epithelial cells is normally tightly controlled. Disturbances can lead to the development of renal cysts or renal cell carcinomas, clinically relevant disease entities, which have so far been considered as being caused by entirely distinct mechanisms. Clear cell renal carcinoma, the most frequent type of renal cancer is associated with inactivation of the von Hippel Lindau (VHL) protein. Genetic defects leading to cystic kidney disease usually affect proteins that play a role in structure or function of primary cilia of renal epithelial cells. Accumulating evidence suggests that the VHL protein also controls cilia function and that its inactivation may result in both malignant or nonmalignant growth of epithelial cells and that this effect is in part mediated through the accumulation of hypoxia-inducible factors. Unraveling the complex role of VHL in renal epithelial cells is likely to shed further insight into mechanism of epithelial growth control, epithelial-mesenchymal transformation, and tumor development.

Saw palmetto extract suppresses insulin-like growth factor-I signaling and induces stress-activated protein kinase/c-Jun N-terminal kinase phosphorylation in human prostate epithelial cells.

A common alternative therapy for benign prostatic hyperplasia (BPH) is the extract from the fruit of saw palmetto (SPE). BPH is caused by nonmalignant growth of epithelial and stromal elements of the prostate. IGF action is important for prostate growth and development, and changes in the IGF system have been documented in BPH tissues. The main signaling pathways activated by the binding of IGF-I to the IGF-I receptor (IGF-IR) are the ERK arm of the MAPK cascade and the phosphoinositol-3-kinase (PI3K)/protein kinase B (PKB/Akt) cascade. We tested the hypothesis that SPE suppresses growth and induces apoptosis in the P69 prostate epithelial cell line by inhibiting IGF-I signaling. Treatment with 150 microg/ml SPE for 24 h decreased IGF-I-induced proliferation of P69 cells and induced cleavage of the enzyme poly(ADP-ribose)polymerase (PARP), an index of apoptosis. Treatment of serum-starved P69 cells with 150 microg/ml SPE for 6 h reduced IGF-I-induced phosphorylation of Akt (assessed by Western blot) and Akt activity (assessed by an Akt kinase assay). Western blot analysis showed that SPE reduced IGF-I-induced phosphorylation of the adapter protein insulin receptor substrate-1 and decreased downstream effects of Akt activation, including increased cyclin D1 levels and phosphorylation of glycogen synthase kinase-3 and p70(s6k). There was no effect on IGF-I-induced phosphorylation of MAPK, IGF-IR, or Shc. Treatment of starved cells with SPE alone induced phosphorylation the proapoptotic protein JNK. SPE treatment may relieve symptoms of BPH, in part, by inhibiting specific components of the IGF-I signaling pathway and inducing JNK activation, thus mediating antiproliferative and proapoptotic effects on prostate epithelia.

797. Human Fibroblasts Expressing Stably-Integrated Telomerase Undergo Non-Malignant Growth Transformation In Vitro That Dramatically Prolongs Transgene Expression and Cell Survival In Vivo

797. Human Fibroblasts Expressing Stably-Integrated Telomerase Undergo Non-Malignant Growth Transformation In Vitro That Dramatically Prolongs Transgene Expression and Cell Survival In Vivo