Synergistic Anti-Cancer Effects of AKT and SRC Inhibition in Human Pancreatic Cancer Cells

PURPOSE: To investigate the effect of combined inhibition of protein kinase B (AKT) and SRC on the growth and metastatic potential of human pancreatic cancer cells. MATERIALS AND METHODS: AKT and SRC were inhibited using 10-DEBC and PP2, respectively. The expression of their messenger RNAs were down-regulated by specific small interfering RNA (siRNA). Changes in pancreatic cancer cell growth and metastatic potential were determined using a cell viability assay and a xenotransplant model of pancreatic cancer, as well as cell migration and invasion assays. Signal proteins were analyzed by Western blot. RESULTS: The inhibitors 10-DEBC and PP2 suppressed cell proliferation in a dose-dependent fashion in pancreatic cancer cell lines MIA PaCa-2 and PANC-1. The simultaneous inhibition of AKT and SRC at low concentrations resulted in a significant suppression of cell proliferation. Knockdown of AKT2 and SRC using siRNAs also significantly decreased cell proliferation. In a pancreatic cancer model, combined treatment with 10-DEBC and PP2 also significantly suppressed the growth of pancreatic cancer. Application of 10-DEBC with PP2 significantly reduced the metastatic potential of pancreatic cancer cells by inhibiting migration and invasion. The combined inhibition suppressed the phosphorylation of mTOR and ERK in pancreatic cancer cells. CONCLUSION: Combined targeting of AKT and SRC resulted in a synergistic efficacy against human pancreatic cancer growth and metastasis.

Successful treatment of vulvodynia with dry needling using a specially designed needle: A case report

Vulvodynia is a chronic pain syndrome in female genitalia in the absence of visible infectious, inflammatory, or neoplastic findings or a clinically identifiable neurological disorder. We report a case of vulvodynia successfully treated with dry needling using a specially designed round needle (Ahn's needle). A 50-year-old woman was seen with 20-year-history of left-sided vulvar pain in the absence of infectious, inflammatory, neoplastic, or neurological disorder. We diagnosed her condition as vulvodynia and conducted dry needling using an Ahn's needle. Dry needling was performed along left upper and middle labiocrural fold. She reported 50% improvement of vulvodynia after the first treatment and 100% improvement after the second treatment. She remained symptom free 9 months after treatment. Our report suggests that dry needling using an Ahn's needle have clinical significance in managing vulvodynia.

A systematic review of the effectiveness and safety of intramuscular stimulation therapy

Intramuscular stimulation (IMS) therapy has been used widely ever since Gunn introduced the effect of IMS in his study in 1980. Usually IMS has been based on Cannon's radiculopathic model, known for its effectiveness in chronic pain relief. In this study we systematically review the effectiveness and safety of IMS. In order to accomplish a systematic review, we searched for IMS-related studies through 12 bibliographical databases and 19 studies were included (4 randomized controlled trials (RCTs), 2 non-RCTs and 13 case reports/studies). Study selection was conducted independently by two researchers based on title and abstract. As a result, most included studies of 16 showed significant improvement in range of motion, decrease of drug consumption as well as pain relief after IMS treatment; the other 3 studies reported adverse events. In terms of the effectiveness of IMS, the results of intervention were good, so we concluded that IMS therapy is a useful method of pain treatment; with respect of safety, few adverse events that could have been caused by IMS were observed. However, it is not certain that there was a causal relationship between IMS and the adverse events that were reported due to a lack of evidence. Therefore, clinicians who have sufficient knowledge and experience of IMS will have to perform the procedure after thorough clinical examinations to determine its appropriateness for target patients. This study provided meaningful data on the current state of IMS treatment. We expect that the result of this study will stimulate further more extensive research on IMS.

Segmental palpation for radiculopathy

The success of intramuscular stimulation relies heavily on a thorough physical examination by a competent practitioner, trained to recognize the physical signs of segmental changes according to segmental innervations of the spinal nerve. These segmental changes are influenced by descending pathways from higher centers of the CNS and/or ascending pathways from peripherally innervated areas. These changes are actual phenomena but are frequently unrecognized by imaging studies such as X-rays, CT scans and MRI. To find abnormal segmental changes, a physical examination with exact palpation is essential. Therefore, in this chapter, we introduce the segmental changes in view of a physical examination and target areas according to dermatomes of the spinal nerve from the cervical and lumbosacral regions.

Segmental palpation for radiculopathy

The success of intramuscular stimulation relies heavily on a thorough physical examination by a competent practitioner, trained to recognize the physical signs of segmental changes according to segmental innervations of the spinal nerve. These segmental changes are influenced by descending pathways from higher centers of the CNS and/or ascending pathways from peripherally innervated areas. These changes are actual phenomena but are frequently unrecognized by imaging studies such as X-rays, CT scans and MRI. To find abnormal segmental changes, a physical examination with exact palpation is essential. Therefore, in this chapter, we introduce the segmental changes in view of a physical examination and target areas according to dermatomes of the spinal nerve from the cervical and lumbosacral regions.

A new method for stimulation of cervical facet joint under ultrasonographic guidance

BACKGROUND: Cervical facet joint needling and stimulation is useful for the management of cervical facet arthropathy, but a direct needling of the joint may injure the capsule and cause post-needling pain.We developed a new approaching technique for cervical facet joint needling and stimulation. METHODS: We retrospectively reviewed medical records of 24 patients with cervical facet arthropathy who underwent facet joint needling and stimulation through oblique posterior approach.Under ultrasonographic guidance, a specially designed dry needle (Ahn's needle) was inserted at midline of posterior neck and advanced obliquely to posterior and lateral side of facet joint.The procedure was completed when a marked reduction in resistance was felt at the tip of the needle.Follow-ups using the numeric rating pain scale (NRS) and the rate of self-rated improvement were conducted at three weeks and about three months after last treatment by telephone interview. RESULTS: Among them, 23 patients were enrolled.The average of NRS decreased from 6.8 +/- 3.0 to 2.7 +/- 3.0 at 3 weeks and to 2.9 +/- 2.0 at 3 months after the last treatment (P < 0.05).The average rate of self-rated improvement was 63.7 +/- 7.2 and 61.6 +/- 3.0% at 3 weeks and 3 months after the last treatment respectively. CONCLUSIONS: Our result suggested that this technique for dry needling around cervical facet joint under ultrasound guidance is one of the successful options to treat neck pain derived from facet joint.

Estimation of the prevalence of osteoarthritis in Korean adults based on the data from the fourth Korea national health and nutrition examination survey

BACKGROUND: This study estimated the number of Korean adults with osteoarthritis from a representative sample. METHODS: We analyzed the data from phase 2 of the fourth Korea National Health and Nutrition Examination Survey conducted in 2008 using surveyfreq procedure of the SAS statistical package and estimated the number of Korean adults who reported that they experienced osteoarthritis lasting for three or more months during the past year (chronic patients) or were suffering from osteoarthritis at the time of survey (current patients). RESULTS: It was estimated that there were 3,597,774 (proportion, 9.8%; 95% confidence interval, 3,238,651-3,956,897) chronic patients and 3,916,417 (10.7%; 3,548,768-4,284,066) current patients among 36,744,994 Korean adults aged 20-89 years in 2008. CONCLUSIONS: Further efforts to investigate exact number of Korean adults with osteoarthritis and improve treatment outcomes of osteoarthritis are needed.

Non-surgical management of temporomandibular joint disorder using specially designed dry needle: A report of 3 cases

Pains derived from the temporomandibular joint are not treated easily. Recently, an arthroscopic surgical management has been reported, but its efficacy has not been proven yet. In this case report, we introduce an effective non-surgical treatment technique for the temporomandibular joint using a specially designed dry needle under ultrasonography guidance. Since the patient has pain related to mouth movement, accompanying decreased mouth opening, clicking sound or crepitus on physical examination, this approach will be helpful for pain relief and for functional recovery of the temporomandibular joint.

Interventional muscle and nerve stimulation for spasmodic torticollis: A case report

A 49-year-old woman with spasmodic torticollis was treated with interventional muscle and nerve stimulation (IMNS). Her neck was tilted to the left, and her chin was rotated and tilted to the right. Based on patient history, physical examination, and X-ray findings, the right C2-3, C3-4, C4-5 and C5-6 facet joints were selected for IMNS treatment. Under ultrasound guidance, an Ahn's Needle (a specially designed needle for IMNS) was inserted from the midline of the posterior neck and advanced toward a point over the capsule of the facet joints. The needle was moved gently forward and backward within a 1-2 mm range until no resistance was felt at the tip. After undergoing three rounds of IMNS treatment, the dystonic features were grossly normal but spontaneous activities of the muscles innervated by C6 remained. Although we did not demonstrate complete improvement of spasmodic torticollis, our report suggests that IMNS has therapeutic value for spasmodic torticollis.

Past, present and future of IMS

IMS is more than a needling technique. It has a background based on physiology, and needling depends upon a detailed knowledge of anatomy. The rationale conforms to Canon's law of denervation supersensitivity. Thus, IMS is a theoretical model that has the support of western physiologists. IMS worked by desensitizing supersensitive body segments. Therefore the technique needs detailed physical examination on segmental innervation area and needling skill to find accurate needling point. IMNS (Interventional Microadhesiolysis and Nerve Stimulation) works for hypersensitive joint soft tissue and FIMS (Fluoroscopy guided Interventional Microadhesiolysis and nerve Stimulation) works for hypersensitive nerve root, whereas classical IMS works for nerve stimulation due to muscle needling. In the future, we can adopt these techniques for brain disease according by Canon's law.

Sonographically assisted minimally invasive release (interventional microadhesiolysis) of the A1 pulley to treat trigger digit

BACKGROUND: We developed a sonographically assisted minimally invasive release technique (entitled as interventional microadhesiolysis) of the A1 pulley to treat trigger digit. This paper introduces the procedure and evaluates the efficacy of the intervention for trigger digit. METHODS: Eleven trigger digits in nine patients were treated with a specially designed needle using ultrasonographic assistance. The technique includes subcutaneous and intrasheath release. Subcutaneous release was performed by obliquely inserting the needle into the interdigital space and advancing it to release the subcutaneous tissue overlying the affected area. If the A1 pulley was not completely released, intrasheath release was performed by advancing the needle into the flexor tendon sheath, and the operator fixed the needle while the digit was passively flexed and extended. RESULTS: After the patients underwent the technique, all of the patients reported a reduction in pain and improved range of motion. CONCLUSIONS: This study suggests that interventional microadhesiolysis is an effective treatment for trigger digit.

Estimated number of self-reported intervertebral disc disorders in Korean adults based on the data from the third Korea national health and nutrition examination survey

BACKGROUND:This study estimated the number of self-reported intervertebral disc disorders in Korean adults from a representative sample. METHODS:We analyzed the data from the third Korea National Health and Nutrition Examination Survey conducted in 2005 using surveyfreq procedure of the SAS statistical package and estimated the number of Korean adults who reported that they experienced intervertebral disc disorders during their lifetime (lifetime patients) and those who reported that they experienced intervertebral disc disorders lasting for three or more months during the past year or were suffering from intervertebral disc disorders at the time of survey (one-year patients). RESULTS:It was estimated that there were 2,653,230 (proportion, 7.4%; 95% CI, 2,490,624-2,815,835) self-reported lifetime patients and 2,250,850 (6.3%; 2,102,714-2,398,986) self-reported one-year patients among 35,719,293 Korean adults aged 20?89 years in 2005. CONCLUSIONS:Further efforts to investigate exact number of Korean adults with intervertebral disc disorders and improve treatment outcomes of intervertebral disc disorders are needed.

Ultrasound-guided cervical facet joint IMS

BACKGROUND:Cervical facet joint stimulation is a good therapeutic option for treating chronic neck pain.Fluoroscopy is the gold standard, as an imaging tool, for performing cervical facet joint stimulation.Ultrasound guided stimulation is safe and accurate, but there have been no reports on using ultrasound guided cervical facet joint stimulation to treat chronic neck pain.We wanted to describe successful ultrasound guided cervical facet joint IMS for treating patients with chronic neck pain. METHODS:Twenty six adult patients were treated with IMS on a cervical facet joint.A low frequency ultrasound system was used (Qsonix by Ultrasonix, Canada with a 6?12 Hz linear probe).The patients were positioned in the prone position with a slight extended neck.A parasagittal posterior view of the cervical spine was obtained with using a sterile technique.This allowed visualization, in a single view, of all the cervical facet joints on the one side.We performed this procedure with a transverse approach after manually palpating the facet joint.This allowed real-time monitoring of the needle along its entire length. RESULTS:The posterior neck pain and the dorsal back pain were both decreased after needle stimulation.Ultrasound guided dry needling could be performed accurately for all the patients. CONCLUSIONS:This is the first description of cervical facet dry needle stimulation under ultrasound guidance for treating chronic neck pain.The advantages of ultrasound guidance include accurate targeting, reducing the unwanted injury and improved patient discomfort.

Successful treatment of spasmodic dysphonia using IMS :A case report

Spasmodic dysphonia is a voice disorder that's characterized by intermittent, involuntary tightening or constriction of the larynx during phonation.This paper describes the case of a 45-yr-old female who suffered from phonation difficulties along with posterior and anterior neck pain.She was diagnosed with adductor type spasmodic dysphonia, which is a chronic disorder involving hyperadduction of the vocal mechanism and a resultant vocal arrest.The neural innervation of the intrinsic laryngeal musculature and the cervical nerves too may well be amenable to intramuscular stimulation therapy.

Subcutaneous botulinum toxin type a injection for chronic medial knee pain with ostheoarthritis

BACKGROUND:This study was designed to evaluate the efficacy of subcutaneous Botulinum toxin type A (BoNT-A) injection for treating chronic medial knee pain with osteoarthritis. METHODS:A randomized, double-blind, placebo-controlled clinical trial was conducted at a university hospital in Korea.The subjects suffering from chronic medial knee pain with osteoarthritis were randomly allocated to either the BoNT-A (treatment, n = 23) group or the normal saline (placebo, n = 27) group.Injections were given to 10 points per unilateral knee along the course of the saphenous nerve.A total of 90 units of BoNT-A (60 units at baseline and 30 units after 1 week) was given for treating unilateral knee pain and a total of 180 units of BoNT-A was given for treating bilateral knee pain.The placebo group received the same volume of normal saline. RESULTS:The Visual Analog Scale (VAS) pain score was significantly decreased in both the BoNT-A and normal saline groups 1, 4 and 12 weeks after injection.After adjusting for covariates, BoNT-A had a 0.788 times higher effect to decrease the VAS score than did normal saline, but the effect was marginally significant (P = 0.050). CONCLUSIONS:Subcutaneous injection along the course of the saphenous nerve significantly reduces chronic medial knee pain. The pain reduction effect of BoNT-A is higher than that of placebo, but the effect is marginally significant

Successful treatment of spasmodic dysphonia using IMS :A case report

Spasmodic dysphonia is a voice disorder that's characterized by intermittent, involuntary tightening or constriction of the larynx during phonation.This paper describes the case of a 45-yr-old female who suffered from phonation difficulties along with posterior and anterior neck pain.She was diagnosed with adductor type spasmodic dysphonia, which is a chronic disorder involving hyperadduction of the vocal mechanism and a resultant vocal arrest.The neural innervation of the intrinsic laryngeal musculature and the cervical nerves too may well be amenable to intramuscular stimulation therapy.

Subcutaneous botulinum toxin type a injection for chronic medial knee pain with ostheoarthritis

BACKGROUND:This study was designed to evaluate the efficacy of subcutaneous Botulinum toxin type A (BoNT-A) injection for treating chronic medial knee pain with osteoarthritis. METHODS:A randomized, double-blind, placebo-controlled clinical trial was conducted at a university hospital in Korea.The subjects suffering from chronic medial knee pain with osteoarthritis were randomly allocated to either the BoNT-A (treatment, n = 23) group or the normal saline (placebo, n = 27) group.Injections were given to 10 points per unilateral knee along the course of the saphenous nerve.A total of 90 units of BoNT-A (60 units at baseline and 30 units after 1 week) was given for treating unilateral knee pain and a total of 180 units of BoNT-A was given for treating bilateral knee pain.The placebo group received the same volume of normal saline. RESULTS:The Visual Analog Scale (VAS) pain score was significantly decreased in both the BoNT-A and normal saline groups 1, 4 and 12 weeks after injection.After adjusting for covariates, BoNT-A had a 0.788 times higher effect to decrease the VAS score than did normal saline, but the effect was marginally significant (P = 0.050). CONCLUSIONS:Subcutaneous injection along the course of the saphenous nerve significantly reduces chronic medial knee pain. The pain reduction effect of BoNT-A is higher than that of placebo, but the effect is marginally significant

The Latest Trend in IMS Therapy for Chronic Pain

No abstract available.

The Deep Dry Needling Techniques, and Interventional Muscle and Nerve Stimulation (IMS) for the Treatment of Chronic Pain / 대한통증학회지

Chronic pain can cause disability, mild to severe suffering and high medical costs. Some unfortunate patient do not improve despite administering conservative treatment and then the various interventional therapies, including oriental medical treatment and/or surgery, and they find themselves in search of a more effective pain relief. Deep dry needling is one of the newer treatment modalities for these patients. The last 10 years have seen a lot of progress in understanding the neural pathways and the type and extent of tissue involvement during chronic pain. This in turn has stimulated the development of new treatment techniques, and deep dry needling is one of them. So, the authors of this paper discuss the individual theories, the characteristics and future directions of several deep dry needling techniques, and we examine the new dry needling technique that has been recently developed in Korea.

Clinical Effect of Fluoroscopy Guided Interventional Muscle and Nerve Stimulation (IMNS) on Intractable Spinal Origin Pain / 대한마취과학회지

BACKGROUND: This study was performed to characterize the long term observations after the use of a round needle for the management of chronic musculoskeletal pain. METHODS: The study subjects were 71 patients with musculoskeletal pain who had failed at least two previous treatments. They received interventional muscle and nerve stimulation (IMNS) using a 0.8 to 1.2 mm diameter dry needle with a streamlined shaped and a round tip from March, 2002 to July, 2002. Patients received IMNS as a bilateral segmental treatment mainly in the paraspinal, sometimes in the radicular region at 2 week intervals. The follow-up rate was 97%. Follow-up occurred at 6 months after the last IMNS treatment. Main outcomes were measured using a pain relief scale and a visual analog scale. RESULTS: Spinal stenosis, Herniated Nucleus Pulposus and an unclassified group (radicular symptoms existed, but no correlatable radiographic findings of radiculopathy were found) produced positive responses whereas fibromyalgia and failed back surgery syndrome did not. CONCLUSIONS: These results reveal that IMNS has a potential value in musculoskeletal pain originating from a spinal nerve root.