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Prostate cancer is the second leading cause of male death from malignant disease in Europe and in the USA. Failure to prevent or eliminate metastatic dissemination is a fundamental problem underlying the current inadequate treatment of prostate cancer, and novel therapeutic strategies are required if this disease is to be successfully managed. No independent markers are yet available to predict the behaviour of any individual prostate cancer, particularly its potential to metastasize, and there is now an urgent prerequisite to identify and characterize genes specifically involved in determining the metastatic phenotype of prostate cancer cells before any biologically appropriate treatment modality can be devised. To identify DNA sequences that trophically promote the metastatic phenotype, we have established a new transfection assay with which to monitor activity of prostate cancer genomic DNA. Rat prostatic G and AT6.1 cell lines derived from the same original Dunning R3327 rat prostatic carcinoma exhibit, respectively, low- and high-metastatic phenotypes when grown in syngeneic Copenhagen rats. Rat mammary epithelial cell line 'Rama 37' derived originally from Wistar-Furth rats yields benign non-metastasizing adenomas when inoculated subcutaneously into syngeneic animals. In this report, the Rama 37 cell line is successfully used as the recipient cell-line for transfected DNA fragments extracted from rat prostatic carcinoma G and AT6.1 cells. New metastatic variants of Rama 37 cells have been generated. Enzymatically fragmented genomic DNA from rat metastatic prostate carcinoma cell lines was co-transfected together with plasmid pSV2neo into parental Rama 37 cells, followed by culture in the presence of Geneticin-G418 to select for the transfected cells. To enable subsequent identification of metastasis-promoting DNA sequences, the fragmented genomic DNA sequences were covalently attached to specifically engineered linker DNA molecules to flank the genomic DNA before transfection. Thereafter, the resulting transfectants were pooled and inoculated into mammary fat pads of female Wistar-Furth rats. Metastases produced by the transfectant cells in vivo were reestablished from secondary tumours and probed for the presence of the specific synthetic oligonucleotide sequences that flanked, and hence identified, the presence of the transfected DNA. These new metastatic cells are shown to provide a sensitive assay system with which to detect DNA sequences responsible for conveying the metastatic phenotype of prostate cancer when inoculated into syngeneic rats.

31P magnetic resonance spectroscopy (MRS) in vivo and in vitro was used to study modulation of host liver (HL) metabolism in rats bearing the MAT-LyLu variant of the Dunning prostate tumour. Animals were inoculated either with 10(6) or 10(7) MAT-LyLu cells, or with saline to serve as controls. Carcass weight in tumour-bearing (TB) animals decreased despite similar food and water intake in both groups. Absence of metastatic tumour cells from HL of all TB animals was confirmed by histological examination. Twenty-one days after inoculation, 31P MRS showed a 2.5-fold increase in [Pi]/[ATP] ratios in HL in vivo (P < 0.001) which was confirmed by 31P MRS of liver extracts in vitro (P < 0.005). Phosphodiester to ATP ratios were significantly increased (P < 0.05) in HL in vivo, but absolute PDE levels were similar in both groups. Phosphomonoester to ATP ratios did not change, although absolute phosphomonoester levels in HL were reduced by -41% (not significant). In HL extracts in vitro, sharp reductions in the levels of glucose-6-phosphate (P < 0.05), fructose-6-phosphate (P = 0.05), phosphocholine (P < 0.001), glycerophosphocholine (P < 0.001), and glycerophosphoethanolamine (P < 0.001) were observed. Electron microscopy revealed increased amounts and altered distribution of rough endoplasmic reticulum in HL. These findings show that experimental prostate cancer significantly affects hepatic phosphorylation status, phospholipid metabolism, and gluconeogenesis in the host animal, and demonstrate the value of combined MRS in vivo and in vitro in monitoring HL metabolism in cancer.

Purpose:To evaluate the long term outcome of intravitreal bevacizumab in the treatment of refractory uveitic macular edema (UME).

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Keywords: Clinical Trial Identifier NCT06038968; Silicone Oils; Silicones; Siloxanes EN Clinical Trial Identifier NCT06038968 Silicone Oils Silicones Siloxanes 252 252 1 10/03/23 20231003 NES 231003 2023 OCT 2 (NewsRx) -- By a News Reporter-Staff News Editor at Clinical Trials Week -- Staff editors report on the newly launched clinical trial, NCT06038968, which has the following summary description: "The goal of this interventional clinical trial is to assess anatomical and functional outcomes of methotrexate use in irrigating fluid during parsplana vitrectomy combined with intrasilicone injection at end of surgery in patients with advanced proliferative diabetic retinopathy. Does methotrexate use in irrigating fluid during parsplana vitrectomy combined with intrasilicone injection at end of surgery improve post operative functional outcome after vitrectomy in patients with advanced proliferative diabetic retinopathy? Does methotrexate use in irrigating fluid during parsplana vitrectomy combined with intrasilicone injection at end of surgery improve post operative functional outcome after vitrectomy in patients with advanced proliferative diabetic retinopathy?. [Extracted from the article]

Atopic keratoconjunctivitis (AKC) is often mistaken for other forms of ocular surface disease, like dry eye. However, misdiagnosis of this fairly common condition may result in devastating ocular morbidity, including corneal scarring, neovascularization, and blindness. The immunopathology of AKC, including its relationship to underlying atopy, requires a unique approach to management. This article will address typical findings of patients with AKC, differential diagnosis, concomitant infections, and systemic and topical treatment of both ocular and skin manifestations. [ABSTRACT FROM AUTHOR]

An Update: Uveitis in Children. SERI and the Asia-ARVO meeting-The only translational ophthalmology meeting in Asia. Interview with the Expert: Prof Wong Tien Yin. [ABSTRACT FROM AUTHOR]

Cancer is a leading cause of death worldwide, and the numbers of new cancer cases are expected to continue to rise. The main goals of cancer therapy include removing the primary tumor, preventing the spread of distant metastases, and improving survival and quality of life for the patients. To attain these goals of cancer therapy, the combination of different chemotherapeutics, as opposed to the conventional single-agent treatment, is an emerging area of research. Given the potential risks of drug toxicity in such treatment, the focus is to have a second compound that increases the anticancer potential of the primary agent but which reduces toxicity. There is an ever growing interest in treatment with natural compounds, such as plant phytoestrogens, as an adjuvant cancer therapy along with conventional cancer therapy. The question remains whether or not adding these compounds to the cancer therapy regimen as a second agent would be beneficial, and if they are safe to be used among cancer patients. The current literature suggests that phytoestrogen treatment is capable of inducing G2/M cell cycle arrest in a number of cancer cell lines, as well as upregulating cell cycle inhibitory molecules. Phytoestrogen therapy has been shown to inhibit inflammation, angiogenesis and metastases in various in vivo tumor models, and pronounced benefits have been observed when combined with radiation therapy. The lack of side effects from phase I and II clinical trials of phytoestrogens in cancer therapy points towards their safety, but to further understand their added benefit clinical studies with large sample sizes are required. We have reviewed the recent research studies in these areas in an attempt to find evidence for their role in cancer therapy as well as safety. [ABSTRACT FROM AUTHOR]

Researchers assessing the demographic statistics of All of Us Research Program participants prioritized enrolling racial, ethnic, and other minorities that, historically, have been underrepresented in clinical trials. The researchers concluded studies need to incorporate more diverse factors as key variables to ensure inclusion and identify barriers that limit research participation. [ABSTRACT FROM AUTHOR]

Au cours du reflux gastro-œsophagien (RGO), la dysphagie est souvent considérée comme un signe d’alarme qui fait craindre la survenue d’un adénocarcinome. Pourtant, la dysphagie est un symptôme relativement banal, dont la fréquence augmente avec l’âge, et qui résulte le plus souvent de l’action combinée de l’œdème et/ou de l’inflammation présentes en cas d’œsophagite, de troubles moteurs œsophagiens consécutifs au reflux, de la présence plus rare d’une sténose peptique ou d’un anneau de l’œsophage et exceptionnellement d’une œsophagite à éosinophiles. La prise en charge de la dysphagie repose sur le traitement optimal du RGO. Les inhibiteurs de la pompe à proton ont également montré leur efficacité en prévention secondaire des récidives. In the course of gastro-oesophageal reflux (GORD), dysphagia is often considered as an alarm sign for a risk of adenocarcinoma. Nevertheless, dysphagia is a rather common symptom, the frequency of which increases with age. It results most often from the combined action of oedema and/or inflammation associated with oesophagitis, oesophageal motility disorders induced by the reflux, the more rare presence of a peptic stenosis or an oesophageal ring and exceptionally of an eosinophilic oesophagitis. The management of dysphagia is based on the optimal treatment of GORD. The proton pump inhibitors (PPI) have also shown their efficacy in the secondary prevention of relapses. [ABSTRACT FROM AUTHOR]

The article offers information on Cultural and Linguistic Diversity (CLD) in Canada. It discusses research on the gaps that may address responsive education for CLD children in the country. It also looks into the concept of multiliteracies theory, practices that promote multilingual literacy, and identity texts of CLD students.

Author(s): Shebin Salim [1]; Md Shahid Alam (corresponding author) [2]; Sonam Ahuja [3]; Kirthi Koka [3]; Marian Pauly [1]; Subramanian Krishnakumar [4]; Bipasha Mukherjee [3] Sarcoidosis is a multisystem granulomatous [...], Purpose: To present the clinical features and management outcomes in a series of patients with orbital and adnexal sarcoidosis. Methods: This was a retrospective analysis of 19 histopathologically proven cases of orbital and adnexal sarcoidosis over the past ten years. The data analyzed included demographic details, clinical and imaging features, and management outcomes. The response to treatment was categorized based on clinical improvement at the last follow-up as complete resolution, partial resolution, or no resolution. Results: There were 15 (78.9%) females and four (21%) males. The mean age at presentation was 51.05 ± 14.35 years. Upper lid swelling was the most common sign (n = 6), followed by lacrimal gland enlargement (n = 5). The specific locations of involvement were orbital soft tissues (n = 8), lid (n = 5), lacrimal gland alone (n = 3), lacrimal sac (n = 1), extra ocular muscles (n = 1), and conjunctiva (n = 1). An incisional biopsy was performed on 16 patients, and an excisional biopsy on three. Of those undergoing excisional biopsy, the lesion was located in the superonasal extraconal space in one and in the superotemporal lid in two. Twelve patients (63.2%) had systemic involvement at presentation. No further treatment was necessary for patients who underwent excisional biopsy. Additional treatments included oral steroids (n = 10) and systemic immunosuppressants (n = 5). Six patients were lost to follow-up. Complete resolution of signs and symptoms was noted in 11 patients (84.6%), while partial resolution was seen in two patients. The mean duration of follow-up was 7.56 ± 12.63 months. Conclusion: Sarcoidosis can affect any part of the orbit or adnexa, with varied presentations depending on the involvement. Excisional or incisional biopsies, along with systemic steroids and immunosuppressants in select cases, remain the mainstay of treatment. Keywords: Adnexa, orbit, sarcoidosis

Author(s): Ankush Kawali (corresponding author) [1]; Aayesha Khanum [2]; Sai B Mishra [1]; Srinivasan Sanjay [1]; Padmamalini Mahendradas [1] Acute retinal necrosis (ARN) is a rare but serious ocular condition [...], Acute retinal necrosis (ARN) is a sight-threatening ophthalmic emergency that requires aggressive treatment to prevent irreversible vision loss. However, primary treatment failure (PTF), where the initial antiviral therapy is ineffective, is a common challenge in ARN management. This comprehensive review examines PTF in ARN, drawing insights from a systematic literature search spanning 1997 to 2022, which identified 35 relevant cases from 23 reports. The analysis focuses on drug resistance patterns, alternative antiviral agents, combination therapies, and emerging treatments. Potential causes of drug resistance, including host factors, viral mutations, and drug-related considerations, are elucidated. Alternative agents such as foscarnet, cidofovir, and brivudine, as well as combination approaches involving systemic and intravitreal administration, high-dose therapy, judicious use of steroids, and potential treatment-related complications, are discussed. The review also highlights emerging therapies, including vaccines, monoclonal antibodies, and natural compounds, offering insights into future directions for addressing this challenging condition. Keywords: Aciclovir, acute retinal necrosis, acyclovir, alternative therapy, cidofovir, drug resistance, foscarnet, high dose, treatment failure, valaciclovir, valacyclovir

Author(s): Nida Khan [1]; Parthopratim Dutta Majumder [2]; Mahesh Janarthanan [3]; Jyotirmay Biswas (corresponding author) [4] Uveitis in children is a challenging condition compounded by difficulty and delay in diagnosis, [...], Purpose: To describe the treatment outcomes of adalimumab in noninfectious pediatric uveitis. Methods: The electronic medical records of children with noninfectious uveitis were reviewed retrospectively. The visual improvement and ocular inflammation were assessed according to the Standardization of Uveitis Nomenclature criteria before and after treatment with adalimumab. Results: Twenty-nine eyes of 16 patients were included. The mean age of children was 9.4 ± 3.8 years. There were eight (50%) males and eight (50%) females. Juvenile idiopathic arthritis was the most common cause of uveitis in these children (N = 10, 62.5%), followed by Behçet&apos;s disease (N = 3, 18.75%) and Vogt-Koyanagi-Harada disease (N = 2, 12.5%). One child (6.25%) was diagnosed with Crohn&apos;s disease. Nine (56.3%) children were previously treated with methotrexate, one each with mycophenolate mofetil (MMF) (6.3%), azathioprine (6.3%), and tofacitinib (6.3%), and one child received MMF followed by azathioprine and cyclosporine before shifting to adalimumab. Three (18.8%) children did not receive prior immunosuppressive therapy. The average number of adalimumab injections given was 20.3 ± 12.0 at an interval of 2 weeks. The mean follow-up duration was 22.2 ± 16.6 months. Disease inactivity was achieved in 28 (96.6%) eyes at last visit (P < 0.001). The best-corrected visual acuity (BCVA) improved from 0.48 ± 0.6 logMAR (logarithm of minimum of resolution) units at baseline to 0.20 ± 0.2 logMAR units at last visit (P = 0.018). Disease remission was achieved in 23 (79.3%) eyes at the third month (P = 0.001). Conclusion: Adalimumab is effective in the treatment of pediatric noninfectious uveitis by achieving disease inactivity, reducing the recurrence rate and improving BCVA. The drug is safe and well tolerated. Keywords: Adalimumab, biologicals, juvenile idiopathic arthritis, pediatric uveitis

Episcleritis and scleritis are ocular conditions that may present with similar signs but have distinctly different visual outcomes and symptoms. While episcleritis is typically a self-limiting condition with a good [...]

Author(s): Sarjak M Shah [1]; Priya Prabhu [1]; Jyotirmay Biswas (corresponding author) [2] Uveitis refers to a diverse group of infectious and noninfectious etiologies that incite inflammation in the vascular [...], The management of intermediate and posterior uveitis poses a significant challenge of achieving adequate drug concentrations in the posterior segment over the chronic nature of the disease. Systemic agents seldom reach effective drug levels, and even with low maintenance or tapering doses, it is hard to avoid systemic toxicity. The use of intravitreal and periocular injections is often unable to prevent recurrences due to their short half-life. Since the emergence of intravitreal implants (Vitrasert, Retisert), it has become possible to circumvent these therapeutic challenges. A detailed review in the PubMed index yielded 155 articles, of which 22 were analyzed based on exclusion criteria. A recent shift from surgically sutured to minimally invasive injectable implants mainly indicated for noninfectious uveitis is evident from the literature. This review article also provides insights into dexamethasone (Ozurdex) and recent fluocinolone acetonide (Yutiq, Iluvien) implants with particular emphasis on their improved safety and efficacy. Dexamethasone implants favor the therapeutic goal of prevention of recurrences, whereas the use of fluocinolone implants helps to attain better visual outcomes due to their longer duration of action. Thus, the review provides recent literature supporting the role and indication of sustained release intravitreal implants in the management of noninfectious intermediate and posterior uveitis. Keywords: Fluocinolone implants, Iluvien, intravitreal implants, noninfectious uveitis, Ozurdex, posterior uveitis, Yutiq

A number of autoimmune diseases may initially present with only ocular manifestations prior to any systemic involvement. Common ocular manifestations of autoimmune diseases include keratitis sicca, peripheral ulcerative keratitis, episcleritis, [...]

A 49-year-old Hispanic female presented for a second opinion regarding chronic floaters and photopsia OU for seven months that were previously diagnosed as a posterior vitreous detachment. Medical history included [...]

Author(s): Raul E Ruiz-Lozano [1,2]; Eugenia M Ramos-Dávila [1]; Alejandro Rodriguez-Garcia (corresponding author) [1] Dear Editor, We read the article 'Surgically induced necrotizing scleritis (SINS): Is it a standalone condition [...]

Earn2CE Credits: (COPE APPROVED) Despite advancements in ocular imaging over the past decade, there is no single parameter used for glaucoma diagnosis. Currently, it is usually made using a Bayesian [...]

Author(s): Kowsigan Magesan [1]; Parthopratim D Majumder (corresponding author) [1]; Mamta Agarwal [1]; Amala E George [1]; Vineeta Nair [1]; Sudha K Ganesh [1]; Jyotirmay Biswas [1] Dear Editor, We [...]

Superior limbic keratoconjunctivitis (SLK) involves inflammation of the upper bulbar and palpebral conjunctiva. One proposed mechanism includes mechanical microtrauma at the superior limbus and bulbar conjunctiva interface. Here, we report [...]

Author(s): Duoduo Wu [1]; Kai En Chan [2]; Blanche Xiao Hong Lim [1,2]; Dawn Ka-Ann Lim [1,2]; Wendy Meihua Wong [1,2]; Charmaine Chai [1,2]; Ray Manotosh [1,2]; Chris Hong Long [...], Corneal neovascularization (CoNV) is a sight-threatening condition affecting an estimated 1.4 million people per year, and the incidence is expected to rise. It is a complication of corneal pathological diseases such as infective keratitis, chemical burn, corneal limbal stem cell deficiency, mechanical trauma, and immunological rejection after keratoplasties. CoNV occurs due to a disequilibrium in proangiogenic and antiangiogenic mediators, involving a complex system of molecular interactions. Treatment of CoNV is challenging, and no therapy thus far has been curative. Anti-inflammatory agents such as corticosteroids are the mainstay of treatment due to their accessibility and well-studied safety profile. However, they have limited effectiveness and are unable to regress more mature neovascularization. With the advent of advanced imaging modalities and an expanding understanding of its pathogenesis, contemporary treatments targeting a wide array of molecular mechanisms and surgical options are gaining traction. This review aims to summarize evidence regarding conventional and emerging therapeutic options for CoNV. Keywords: Anti-VEGF, cornea, corneal neovascularization, gene therapy

It is important that clinicians are prepared with alternative methods for patients experiencing refractory CME after failed improvement with the agents that are most frequently used. Pseudophakic cystoid macular edema [...]

Often, what's found at clinical presentation results in needing additional laboratory testing and/or imaging studies. In Part 1 of this series last month, we explored how to implement these procedures [...]

For many optometrists, the most valuable resource we can save is our time. In some situations, clinicians may choose to buy themselves time between exams by performing a more brief, [...]