Autologous Immune Enhancement Therapy in Recurrent Ovarian Cancer with Metastases: A Case Report

Current therapeutic modalities for ovarian cancer such as chemotherapy, radiotherapy and surgery have been reported to yield only marginal success in improving survival rates of patients and have associated adverse effects. We report here a case of recurrent stage IV ovarian cancer, treated with cell-based autologous immune enhancement therapy (AIET) along with chemotherapy and followed up for 18 months. A 54-year-old female was diagnosed with a recurrence of ovarian carcinoma 1 year after initial surgical removal followed by chemotherapy for stage IIIC ovarian carcinoma. When diagnosed in 2010 with recurrence, she had liver and spleen metastases with a CA-125 level of 243 U/ml and a stage IV clinical status. Six infusions of AIET using autologous in vitro expanded and activated natural killer (NK) cells (CD3–CD56+) and activated T lymphocytes (CD3+CD56+) were administered in combination with 6 cycles of chemotherapy with carboplatin and doxorubicin. Following this treatment, CA-125 decreased to 4.7 U/ml along with regression of the metastatic lesions and an improved quality of life. No adverse reactions were reported after the AIET transfusions. Eighteen months of follow-up revealed a static nonprogressive disease. Combining AIET with chemotherapy and other conventional treatments has been found to be effective in our experience, as reported earlier, even in patients with advanced ovarian cancer, and we recommend this strategy be considered in treating similar cases

Synthesis and Evaluation of Anisomelic acid-like Compounds for the Treatment of HPV-Mediated Carcinomas

The vast majority of cervical and 75% of oropharyngeal carcinomas are triggered by infection with a type of high-risk oncogenic human papillomavirus (HPV). It is well-known that E6 and E7 oncoproteins are critical for viral-induced cancer, and hence, they represent valuable targets for therapeutic intervention in HPV-mediated cancers. Our earlier research on the cembranoid, anisomelic acid (AA) showed that, AA has the potential to induce apoptosis in HPV cells by the depletion of E6 and E7 oncoproteins. The present study describes the structure-activity relationship and the evaluation of synthetic AA like compounds, i.e simplified cembranoid-like structures, as HPV inhibitors against some papilloma cell lines. Both from experimental and computational results, we observed that these compounds induced apoptosis by the same E6/E7-based mechanism as AA, but at earlier time points, thus being far more effective than AA. Further, the data indicated that only part of the structure of AA is required for the molecular action. Based on these results, we identified some novel and potential compounds for specific treatment of HPV-associated carcinomas

Five-year trend of competitiveness and knowledge-gaining attitude of university students; Evaluation based on an event of continuing health sciences education

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Cell Based Autologous Immune Enhancement Therapy (AIET) after Radiotherapy in a Locally Advanced Carcinoma of the Cervix

Radiotherapy is the primary form of treatment in patients with locally advanced cervical carcinoma. However for residual disease in the form of the persistent lymph nodes, surgery or chemotherapy is recommended. As surgery is not acceptable by every patient and chemotherapy has associated side effects, we hereby report the positive outcome of in vitro expanded natural killer cell and activated T lymphocyte based autologous immune enhancement therapy (AIET) for the residual lymphadenopathy in a patient with locally advanced cervical cancer after radiation. After six transfusions of AIET, there was complete resolution of residual lymph nodes and there was no evidence of local lesion. The patient also reported improvement in quality of life. As AIET has been reported as the least toxic among the available therapies for cancer, combining AIET with conventional forms of therapy in similar patients might not only improve the outcome but may also help the patients achieve a good quality of life

Role of tissue engineered buccal mucosa for treatment of urethral stricture

Cell based therapies in Urology: Cell based therapy for tissue engineering in urology, like in other branches of medicine uses the principles of cell transplantation, materials science, and biomedical engineering to develop biologic substitutes that can restore and maintain function of the damaged or lost genitourinary organs. Most current strategies for tissue engineering depend on a sample of autologous cells from the diseased organ of the host. However in cases where primary autologous cells cannot be expanded, pluripotent stem cells are an ideal source. Biomaterials play a major role in genitourinary tissue engineering. They are used to replace biologic and mechanical functions of the native extracellular matrix. Three classes of biomaterials have been used for the engineering of genitourinary tissues: naturally derived materials, such as collagen and alginate; acellular tissue matrices, such as bladder submucosa and synthetic polymers, such as polyglycolic acid [1]. A lot of research is ongoing in urethral regeneration by tissue engineering and cell based therapy. Tubularized collagen matrices seeded with autologous cells are used to regenerate the urethra [2]. Urinary Bladder reconstruction is possible with bladder shaped biodegradable scaffold seeded with autologous urothelial cells and smooth muscle cells [3]. Ureteral acellular tubular grafts have been used to replace ureteral loss but with poor functional results [4]. Cell-seeded biodegradable polymer scaffolds have been used with more success to reconstruct ureteral tissues [3]. The kidney is the most challenging organ in the genitourinary system to reconstruct because of its complex structure and function. Cell based therapies are used for creation of functional renal structures in vivo. Renal tubular cells have been harvested, expanded in culture and seeded on to a tubular device to function as nephron [5]. The expansion of this system to larger three-dimensional structures is the next challenge awaiting researchers in the urogenital tissue engineering field. Genitalia reconstruction is also possible with cell therapy. Engineered penile prosthesis can be reconstructed by culturing autologous chondrocytes which are seeded onto a Poly-glycolic acid scaffold and then implanting the scaffold into the corporal space of penis [6]. Microencapsulated Leydig cells in animal studies have been used to replace or supplement testosterone in testicular failure [7]. Cell therapy techniques are also used for treatment of urinary incontinence, vesicoureteric reflux by injecting cultured myoblasts or adipocytes [5]. The major limitation in engineering solid organs is the vascularisation of the regenerated tissue. Recent developments in angiogenesis research [8] may provide answer to this complex problem and accomplish the goal. Most of the research to date in urological tissue engineering is done in animals. Before these engineering techniques can be applied to humans, further studies need to be performed. Buccal Mucosal Epithelium for repair of the short segment urethral stricture: Urethral stricture is the narrowing of the lumen of the urethra which occurs as a terminal event secondary to many etiologies. Patients present with difficulty in voiding urine. There are endoscopic and open surgical reconstructive procedures to treat this disorder. Endoscopic treatment is often temporary and eventually results in recurrence of the disease. Many open surgical procedures have been described but none of the procedures offer permanent cure. The use of buccal mucosal grafts for stricture repair is in practice [9,10] with considerable success. However the donor site morbidity and complications like stricture recurrence with the present techniques [11,12] warrant the advent of novel techniques. The use of buccal mucosal cells which can be obtained by harvesting a 2mm x 2mm tissue bit compared to that of 5-6cm tissue usually harvested in conventional techniques for a graft and the culture-expansion of these cells in a suitable in vitro scaffold which can also act as a substrate after transplantation in vivo for optimal repair provides a viable option. Preliminary results of the application of autologous human buccal epithelial cells expanded & encapsulated in a nanopolymer scaffold after confirmation of their phenotype and genotype, in a male patient with inflammatory urethral stricture have been encouraging. This approach we have named as the Buccal Epithelium Expanded & encapsulated in Scaffold - Hybrid Approach to Urethral Stricture (BEES-HAUS) and is seemingly a promising one and further studies are needed for its validation

Potential Effects of Nichi Glucan as a Food Supplement for Diabetes Mellitus and Hyperlipidemia: Preliminary Findings from the Study on Three Patients from India

Beta Glucan food supplements have been reported to be of benefit in diabetes and hyperlipidemia. We report a pilot study of the effects of Nichi Glucan, 1, 3-1, 6 Beta Glucan food supplement, in lowering the blood glucose and lipid levels in three patients with noninsulin-dependent diabetes mellitus (NIDDM) from India. These patients had increased blood glucose and lipid levels inspite of routine antidiabetic and lipid level lowering medications. Each of the participants took 1.5 g of Nichi Glucan per day with food for two months along with their routine medications. The relevant parameters to assess glycemic status and lipid levels were calculated at the baseline and at the end of two months. After two months of continuous consumption, in one patient, the HbA1c decreased from 9.1% to 7.8%, and the glycemic target of HbA1c <6.5% laid down by the International Diabetes Federation was reached in two patients. Lipid levels also decreased significantly. Based on our findings, Nichi Glucan food supplement can be considered along with routine medications in patients with Type II diabetes with hyperlipidemia. Further studies are needed to validate the results

β-glucans: wide-spectrum immune-balancing food-supplement-based enteric (β-WIFE) vaccine adjuvant approach to COVID-19

Conventional vaccines to combat COVID-19 through different approaches are at various stages of development. The complexity of COVID-19 such as the potential mutations of the virus leading to antigenic drift and the uncertainty on the duration of the immunity induced by the vaccine have hampered the efforts to control the COVID-19 pandemic. Thus, we suggest an alternative interim treatment strategy based on biological response modifier glucans such as the Aureobasidium pullulans AFO-202-derived β-glucan, which has been reported to induce trained immunity, akin to that induced by the Bacille Calmette-Guérin vaccine, by epigenetic modifications at the central level in the bone marrow. These β-glucans act as pathogen-associated molecular patterns, activating mucosal immunity by binding with specific pathogen recognition receptors such as dectin-1 and inducing both the adaptive and innate immunity by reaching distant lymphoid organs. β-Glucans have also been used as immune adjuvants for vaccines such as the influenza vaccine. Therefore, until a conventional vaccine is widely available, an orally consumable vaccine adjuvant that acts like biosimilars, termed as the wide-spectrum immune-balancing food-supplement-based enteric (β-WIFE) vaccine adjuvant approach, with well-reported safety is worth in-depth investigation and can be considered for a clinical trial

Autologous Immune Enhancement Therapy for cancer using NK cells and CTLs without feeder layers; our six year experience in India

Background: Autologous Natural Killer (NK) cells and Cytotoxic T Lymphocytes (CTLs) based immune-cell therapy, otherwise called as Autologous Immune enhancement therapy (AIET), though has been in clinical practice in several developed nations since early 90s, in India it is in infancy due to lack of technological knowhow. Our institute has been providing the AIET cell expansion services since 2005 and we here in report our experience in 30 such patients of both solid tumours and hematological malignancies.Materials and Methods: The number of AIET transfusions in each patient ranged from one to six. All the patients included had Stage III to IV malignancy. AIET was either given along with the chemotherapy or after the completion of a minimum of six cycles of chemotherapy in all the patients. 70 ml of Peripheral Blood was collected each time. The protocol followed was as per Terunuma et al (Breast Cancer 2010) which uses only the patients’ autologous plasma for expansion of the Natural Killer Cells and Cytotoxic T lymphocytes from the peripheral blood. The cells were cultured for a period of 10 to 16 days and then transfused to the patients intravenously. The cells were subjected to Flow cytometry before and after the in vitro expansion. Feeder layers were not used in the procedure of in vitro expansion at any stage.Results: The percentage of NK cells and CTLs after expansion by flow cytometry ranged from 60 to 82 %. There were no adverse reactions in any of the patients following transfusion. The mean prolonged survival time was 15 months and 27% of the patients had Static non-progressive disease after the therapy. Two patients reported significant decrease in Cancer marker levels after AIET and among the terminally ill, two had more than two years survival. All the patients reported improvement in quality of life and resumption of appetite following AIET. Conclusion: Optimal in vitro expansion of NK cells and CTLs of patients with stage III-IV cancer either concurrently or after chemotherapy could be accomplished using autologous serum without use of feeder layers. The In vitro expanded NK cells and CTLs when given intravenously decrease the tumor size and prolong the survival without any adverse effect in our experience