Increasing Engagement during Online Learning through the Use of Interactive Slides.

It is difficult in asynchronous online instruction to keep students engaged and motivated. The rapid and unexpected nature of the move to online instruction has meant that the content presented to students has been primarily static and linear. Thus, there is a need for creative pedagogical approaches that re-create some level of the laboratory experience. One economical and accessible approach to building an interactive lab experience is making web-based interactive slides. In the virtual spaces created by this approach, students can explore different modalities of content in a nonlinear and asynchronous manner. We hope that this approach will make the learning process easier and more enjoyable for students while simultaneously making the complex content normally covered in microbiology labs more approachable. In this article we provide detailed instructions for producing web-based interactive slides as well as an example interactive slide that encompasses content that might normally be presented in an introductory microbiology class.

Treatment of cervix carcinoma FIGO IIIb with Photofrin II as a radiosensitizer: a case report.

Cervical cancer is the fourth-most common type of cancer and cause of death in women. Human papilloma virus (HPV) infection is responsible for over 90% of cervical cancers. The recommended treatment is multidisciplinary, consisting of a combination of surgery, chemotherapy, and radiation therapy. The standard treatment in advanced stages, such as FIGO IIIb, is radio-chemotherapy with overall 5-year survival of 32%. Photofrin II has been demonstrated to serve as a specific and selective radiosensitizing agent in both in vitro and in vivo tumor models, admitted for radiation therapy. We describe a patient with advanced cervical carcinoma (squamous cell) who contacted us for further therapy in 2003. Staging included a gynecological examination, colonoscopy, explorative laparotomy, biopsy and pelvic MRI. The explorative laparotomy showed enlarged pelvic and para-aortal lymph nodes. The histologic examination described tumor infiltrated, positive lymph nodes (Stage FIGO IIIb). Contrary to recommendations, the patient refused standard treatment with a combination of chemotherapy and radiotherapy, but accepted a combined treatment of Photofrin II as a radiosensitizer and a radiotherapy procedure. She underwent irradiation with a 50.4 + 14 Gy boost with fractionation of 1.8 Gy day-1 for 5 days per week; the boost was given with 2 Gy fractions. She was injected with a single intravenous dose in a slow infusion (30 min) of 1 mg kg-1 of Photofrin II 24 h prior to radiation therapy. A localized relapse in the cervix appeared after 30 months, and was resected by hysterectomy. The patient is still alive with no evidence of disease after 15 years.

Management of Peripheral Neuropathy Induced by Chemotherapy.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is considered a severe side effect of therapeutic agents with limited treatment options. The incidence of CIPN in cancer patients is approximately 3-7% in cytostatic monotherapy and as high as 38% in cases of polychemotherapy. The prevalence of CIPN was found to be 68% within the first month of chemotherapy treatment. In some cases, CIPN can resolve, partially or completely, after completion of the treatment; in other cases, it can remain for a long time and affect the patient's quality of life. OBJECTIVE: The aim of this study is to present up-to-date data regarding available treatment options for the management of CIPN. MATERIALS AND METHODS: The up-to-date guidelines of ESMO (European Society for Medical Oncology), ASCO (American Society of Clinical Oncology), ONS (Oncology Nursing Society), NCI (National Cancer Institute), and NCCN (National Comprehensive Cancer Network) were reviewed and included in the manuscript. RESULTS: The use of tricyclic antidepressant (TCA), selective serotonin norepinephrine reuptake inhibitor (SSNRI), pregabalin, and gabapentin are recommended as first-line treatment. Other treatment options were offered as second and third lines of treatment (lidocaine patches, capsaicin high-concentration patches, tramadol, and strong opioids, respectively); however, lower significance was demonstrated. Inconclusive results were found in the use of cannabinoids, drug combinations, antiepileptics, antidepressants, and topical drugs. CONCLUSION: TCA, other antidepressants, and opioids could be recommended as treatment. Yet, we could not recommend an ideal therapeutic agent for the prevention or treatment of CIPN. Therefore, CIPN continues to be a challenge to clinicians and our patients.

Glioblastoma Multiforme, Diagnosis and Treatment; Recent Literature Review.

BACKGROUND: Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor, with an incidence of 3.19 cases per 100,000 person years and remarkably poor prognosis showing a 5-year survival rate of 4-5%, and only a 26-33% survival rate at 2 years in clinical trials. OBJECTIVE: In this paper, we review the different types of treatment modalities based on the relevant databases. Methods of diagnosis will be described briefly. METHOD: Systemic compilation of the relevant literature. RESULTS & CONCLUSION: Today's treatments cannot cure GBM patients but only extend their overall survival. The use of chemoradiation, immunotherapy, and radio sensitizers as an adjuvant therapy cannot reduce the high rates of recurrence within a few months after treatment. Radiotherapy will remain the backbone of the treatment but new treatment modalities must be developed.

The Possible Role of Infertility Drugs in Later Malignancy: A Review.

BACKGROUND: Some 15% of all couples in the industrialized world suffer from infertility. Accordingly, any possible life-long morbidity that may result from treatments for infertility presents a significant concern to public health. The use of medications for infertility is specifically relevant to their possible effects on the classical target tissues for hormones involved in the sex axes, i.e., uterus, ovaries, and breast, but may have an effect on other organs, which harbor receptors for some of the hormones involved in reproduction. When one deals with the effect of treatment for infertility on the occurrence of malignant conditions, there is no doubt that certain malignancies tend to occur more frequently in women who suffered from and/or were treated for infertility. OBJECTIVE: To review the accumulated data on the association of treatments for infertility with subsequent malignancies both in the classical target organs of sex steroids and in non-target organs. METHODS: Systematic compilation of the relevant literature. RESULTS & CONCLUSION: Contrary to popular believes, treatment for infertility is associated with very little increase in malignacies.

An update on Curcuma as a functional food in the control of cancer and inflammation.

PURPOSE OF REVIEW: Curcumin, commonly known as turmeric, is a spice that comes from the root Curcuma longa. The present article presents an update of new studies of curcumin activities as tested in anticancer models from 2011 to 2015. RECENT FINDINGS: Evidence from in-vitro and in-vivo research, together with clinical trials conducted over the past few decades, substantiates the potential of curcumin as an anticancer and anti-inflammatory agent. The development of formulations of curcumin in the form of nanoparticles, liposomes, micelles, or phospholipid complexes to enhance its bioavailability and efficacy are still in the early stages. Clinical trials with curcumin indicate safety, tolerability, and nontoxicity. However, the efficacy is questionable, based on the small numbers of patients in each study. SUMMARY: The laboratory and the clinical studies until 2011 were summarized in a review published in this journal. An update of the new studies and knowledge from 2011 to March 2015 focuses on new ways to overcome its low bioavailability and data from clinical trials.

Curcuma as a functional food in the control of cancer and inflammation.

PURPOSE OF REVIEW: Several nutritional compounds are the focus of public attention because of their potential beneficial health effects. Turmeric is a spice that comes from the root Curcuma longa. Extensive research over the past half century and especially in recent years has revealed important functions of curcumin and a timely review of clinical state-of-the-art using curcumin. RECENT FINDINGS: In-vitro and in-vivo research has shown various activities, such as anti-inflammatory, antiviral, antifungal, cytokines release, antioxidant, immunomodulatory, enhancing of the apoptotic process, and antiangiogenic properties. Curcumin also have been shown to be a mediator of chemo-resistance and radio-resistance. SUMMARY: Various in-vitro and in-vivo and scarce number of clinical studies on curcumin were identified. The various effects and properties of curcumin are summarized in this review, including preclinical and especially clinical studies. This review concentrates on recent knowledge and research with curcumin clinical applications, and clinical studies, focusing on studies published between 2008 and 2011 demonstrating the gap between preclinical and clinical research.

Regional hyperthermia combined with chemoradiotherapy in primary or recurrent locally advanced pancreatic cancer : an open-label comparative cohort trial.

PURPOSE: To evaluate the therapeutic effect of delivering regional hyperthermia (HT) plus chemoradiotherapy (CRT) in patients suffering from locally advanced unresectable pancreatic cancer (LAPC). METHODS: Between January 2000 and December 2008, 68 patients affected by primary (56/68) or recurrent (12/68) LAPC were treated either with CRT alone or CRT plus HT. Radiotherapy (RT) consisted of 3D conformal irradiation of tumor and regional lymph nodes (dose ranged from 30 Gy/10 fractions to 66 Gy/33 fractions). Chemotherapy (CT) consisted of gemcitabine (GEM) alone or in association with either oxaliplatin, cisplatin, or 5-FU. HT was delivered twice a week, concomitant with RT. RESULTS: In the current study, 60 of the original 68 patients were included. Median overall survival (OS) was 15 months in the HT group versus 11 months in the control group (log-rank test: p = 0.025). HT did not increase CRT toxicity. CONCLUSION: HT can be added safely to CRT in LAPC, thus, resulting in slightly prolonged survival in certain cases.

Intrathecal trastuzumab (Herceptin) and methotrexate for meningeal carcinomatosis in HER2-overexpressing metastatic breast cancer: a case report.

Leptomeningeal carcinomatosis represents a rare manifestation of metastatic breast cancer (MBC). We herewith report on a patient suffering from HER2 overexpressing MBC who received intrathecal methotrexate and trastuzumab for meningeal carcinomatosis. A 48-year-old woman was diagnosed with breast cancer in December 2002. Following surgery, six cycles of adjuvant FE100C plus irradiation and, subsequently for 1 year, trastuzumab were given. As a result of disseminated metastatic spread in October 2005, the patient received whole-brain radiotherapy for symptomatic central nervous system involvement, and was put on several trastuzumab-based combination regimens (capecitabine, vinorelbine, paclitaxel). In June 2006, the patient developed clinical signs of terminal cone involvement with overflow incontinence and paraparesis of the legs. Immediate radiation led to partial relief from clinical symptoms. Subsequently, the patient was put on the tyrosine kinase inhibitor lapatinib and capecitabine (August to October 2007), but on November 6th the patient suffered again from overflow incontinence and weakness of the legs. Failing to respond to lapatinib, the patient received gemcitabine/cisplatin and, additionally, was recommenced on intravenous trastuzumab. Owing to progressive leptomeningeal disease, the patient received repeated doses of intrathecal methotrexate and trastuzumab. Within 2 weeks and four intrathecal treatments, cerebrospinal fluid cytology showed the absence of tumor cells. Moreover, a striking clinical improvement with resolution of the paraparesis of the legs and overflow incontinence was observed. This case report gives details regarding the clinical course of a breast cancer patient who received intrathecal trastuzumab and methotrexate via lumbar puncture for meningeal carcinomatosis of HER2-overexpressing MBC.

The effect of radio-adaptive doses on HT29 and GM637 cells.

BACKGROUND: The shape of the dose-response curve at low doses differs from the linear quadratic model. The effect of a radio-adaptive response is the centre of many studies and well known inspite that the clinical applications are still rarely considered. METHODS: We studied the effect of a low-dose pre-irradiation (0.03 Gy - 0.1 Gy) alone or followed by a 2.0 Gy challenging dose 4 h later on the survival of the HT29 cell line (human colorectal cancer cells) and on the GM637 cell line (human fibroblasts). RESULTS: 0.03 Gy given alone did not have a significant effect on both cell lines, the other low doses alone significantly reduced the cell survival. Applied 4 h before the 2.0 Gy fraction, 0.03 Gy led to a significant induced radioresistance in GM637 cells, but not in HT29 cells, and 0.05 Gy led to a significant hyperradiosensitivity in HT29 cells, but not in GM637 cells. CONCLUSION: A pre-irradiation with 0.03 Gy can protect normal fibroblasts, but not colorectal cancer cells, from damage induced by an irradiation of 2.0 Gy and the application of 0.05 Gy prior to the 2.0 Gy fraction can enhance the cell killing of colorectal cancer cells while not additionally damaging normal fibroblasts. If these findings prove to be true in vivo as well this may optimize the balance between local tumour control and injury to normal tissue in modern radiotherapy.

Radiochemotherapy in combination with regional hyperthermia in preirradiated patients with recurrent rectal cancer.

BACKGROUND AND PURPOSE: Encouraging results of phase II studies combining chemotherapy with radiotherapy have been published. In this study, the results of a multimodal salvage therapy including radiochemotherapy (RCT) and regional hyperthermia (RHT) in preirradiated patients with recurrent rectal cancer are reported. PATIENTS AND METHODS: All patients enrolled had received previous pelvic irradiation (median dose 50.4 Gy). The median time interval between prior radiotherapy and the onset of local recurrence was 34 months. The combined treatment consisted of reirradiation with a median dose of 39.6 Gy (30.0-45.0 Gy), delivered in fractions of 1.8 Gy/day. 5-fluorouracil was given as continuous infusion 350 mg/m(2)/day five times weekly, and RHT (BSD-2000 system) was applied twice a week within 1 h after radiotherapy. The primary endpoint was local progression-free survival (LPFS); secondary endpoints were overall survival, symptom control, and toxicity. RESULTS: 24 patients (median age 59 years) with a previously irradiated locally recurrent adenocarcinoma of the rectum were enrolled. The median LPFS was 15 months (95% confidence interval 12-18 months] with a median follow-up of 27 months (16-37 months). The overall 1-year and 3-year survival rates were 87% and 30%, respectively. Pain was the main symptom in 17 patients. Release of pain was achieved in 12/17 patients (70%). No grade 3 or 4 hematologic or skin toxicity occurred. Grade 3 gastrointestinal acute toxicity was observed in 12.5% of the patients. Paratumoral thermometry revealed a homogeneous distribution of temperatures. CONCLUSION: RCT combined with RHT is an efficient salvage therapy showing high efficacy with acceptable toxicity and can be recommended as treatment option for this unfavorable group of preirradiated patients with local recurrence of rectal cancer.

Irradiation treatment of laryngeal cancer in a patient with an implantable cardioverter-defibrillator (ICD).

BACKGROUND: Due to an aging population the incidence of both cardiac and tumor-related illnesses is increasing. A problem may arise if radiotherapy is necessary in close anatomic proximity to an implantable cardioverter-defibrillator (ICD). These highly precise devices may respond to ionizing radiation with a loss of function or uncontrolled stimulation, with both effects being potentially life threatening. Available guidelines recommend the dose maximum to a pacemaker to be cumulative below 2 Gy. For most patients undergoing radiation therapy of the neck or of the chest this limit is exceeded, thus making a removal of the device and an implantation of an external ICD necessary. CASE REPORT: A patient with severe cardiac problems underwent an implantation of an ICD. However, a recurrence of a laryngeal cancer was diagnosed. The irradiation dose after resection was 60 Gy to the tumor region and 50 Gy to the lymph nodes. Irradiation peakload to the ICD was calculated to be 2.5 Gy. This dose was verified with thermoluminescence measurements. The ICD was externally deactivated during the sessions of irradiation. Device checks demonstrated no malfunction. CONCLUSION: Even though the dose limits of the ICD of 2 Gy were exceeded, the device demonstrated a regular function during and after radiotherapy.

Feasibility of photofrin II as a radiosensitizing agent in solid tumors--preliminary results.

BACKGROUND: Photofrin II has been demonstrated to serve as a specific and selective radiosensitizing agent in in vitro and in vivo tumor models. We aimed to investigate the feasibility of a clinical application of Photofrin II. MATERIAL AND METHODS: 12 patients were included in the study (7 unresectable solid tumors of the pelvic region, 3 malignant gliomas, 1 recurrent oropharyngeal cancer, 1 recurrent adenocarcinoma of the sphenoid sinus). The dose of ionizing irradiation was 30-50.4 Gy; a boost irradiation of 14 Gy was added for the pelvic region. All patients were intravenously injected with 1 mg/kg Photofrin II 24 h prior to the commencement of radiotherapy. Magnetic resonance imaging (MRI) controls and in some cases positron emission tomography (PET) were performed in short intervals. The mean follow-up was 12.9 months. RESULTS: No major adverse events were noted. Minor adverse events consisted of mild diarrhea, nausea and skin reactions. A complete remission was observed in 4/12 patients. A reduction in local tumor volume of >45% was achieved in 4/12 patients. Stable disease was observed in 4/12 patients. 1 patient showed local disease progression after 5 months. CONCLUSION: The early follow- up results are encouraging regarding the feasibility of the application of Photofrin II as a radiosensitizing agent.

Optimized radiation of pelvic volumes in the clinical setting by using a novel bellyboard with integrated gonadal shielding.

The purpose of this study was to determine the feasibility of a custom-made, modified bellyboard to reduce radiotherapy side effects on small bowel, bladder, skin, and male gonads. Two groups of 10 consecutive patients each were treated from January 2003 through April 2003 with neoadjuvant (45 Gy) or adjuvant (54 Gy) radio(chemo)therapy in single fractions of 5 days a week 1.8 Gy for rectal carcinoma, using a photon energy of 15 MV. One group was positioned in a prone position without an immobilization device, the other group was positioned on our bellyboard. Treatment planning was calculated by using a 4- and a 3-field box technique. Differences in the dose of organs of risk were calculated. For 1 male patient, a gonadal shielding was developed and integrated. All patients examined with the bellyboard demonstrated an anterior and cranial dislocation of the small bowel. Using a 4-field box, the mean dose to the small bowel of patients treated on our bellyboard was 56.5% as compared to 63.1% when treated without the bellyboard. When a 3-field box was used, the mean dose to the small bowel was 52.4% when the bellyboard was used, as compared to a mean dose of 63.1% without the bellyboard. Regarding the dose volume effects to the bladder, the mean dose for patients treated with a 4-field box was about 14.5% higher as compared to patients treated with a 3-field box. The mean dose to the hip joints and skin also depended on the radiation technique. The patient who received gonadal shielding received a maximal total gonadal dose of about 75.0 cGy in single fractions of maximal 3.0 cGy (TL-dosimeters). Daily setup variations evaluated by a beam's-eye view were similar in both groups and ranged from 0.5 cm 1.0 cm. For daily use, our bellyboard appears to be an ideal compromise due to effectiveness, its easy handling, and reproductive positioning; moreover, it can also be used in combination with gonadal shielding.

Photofrin as a radiosensitizer in an in vitro cell survival assay.

Chemical modifiers (radiosensitizers) are used in order to increase the efficacy of radiotherapy. The use of Photodynamic Therapy for tumor treatment, especially with Photofrin II, is also known. At present, no chemical modifier has been found to act as a selective radiosensitizer. Experiments using several series of cell lines were performed; human bladder cancer cell line (RT4), colon adenocarcinoma cells (HT-29), and the glioblastoma cells (U-373 MG) were investigated, with and without incubation with Photofrin II, before irradiation. The irradiation was performed using doses ranging from 0 to 8Gy. Colony forming tests were applied to determine the efficiency of Photofrin II as a radiation sensitizer in comparison to irradiation alone. Two of the cell lines tested, cultures of the RT4 and U-373 MG, treated with Photofrin II prior to radiation, showed cell survival lower than cultures untreated with Photofrin II but irradiated under identical conditions. For the HT-29 cells, the results did not differ between the two groups (with and without Photofrin). The results of this study showed that Photofrin II can act, under certain conditions as a tumor radiosensitizer.

Overexpression of von Willebrand factor is an independent risk factor for pathogenesis of intimal hyperplasia: preliminary studies.

OBJECTIVE: Deposition of von Willebrand factor (vWF) is increased in hyperplastic intima of grafts, vWF levels are elevated in patients with cardiovascular diseases, and there is resistance to progression of atherosclerosis in pigs with von Willebrand disease. We hypothesize that increased expression of endothelial vWF has mitogenic effects on smooth muscle cell (SMC) proliferation. METHODS: In an in vitro study, mouse aortic smooth muscle cells (SMC) were exposed to vWF in various concentrations (0, 5, 20, 100, 500, and 1000 ng/mL). DNA synthesis of SMC was measured with (3)H-thymidine incorporation. In an in vivo study, 108 mice from inbred strains of C57BL/6J (control) and RIIIS/J (characteristic of low plasma vWF) underwent carotid artery ligation (flow cessation model) and were divided into three groups: C57BL/6J, RIIIS/J, and RIIIS/J treated with desmopressin (DDAVP; intraperitoneal injection at 3 micro g/kg/d). At 2 and 4 weeks, carotid arteries were harvested for analysis with immunohistochemical analysis, morphometric studies, and reverse transcriptase polymerase chain reaction; plasma vWF was measured with an enzyme-linked immunosorbent assay. RESULTS: In vitro SMC proliferation showed a positive dose-response curve with vWF stimulation. Intimal hyperplasia (IH) in carotid arteries was prominent in C57BL/6J mice, absent in RIIIS/J mice, and moderate in RIIIS/J treated with DDAVP (intima-media ratio, 71% +/- 18%, 0, and 32% +/- 12%, respectively; P <.01). vWF deposition occurred in all hyperplastic intima subjacent to intact endothelium. Plasma vWF correlated with degree of IH (110% +/- 10%, 21% +/- 7%, and 45% +/- 8%, respectively; P <.05). vWF-messenger RNA was 9 times higher in carotid arteries of C57BL/6J mice and 4 times higher in RIIIS/J with DDAVP, compared with RIIIS/J. CONCLUSIONS: vWF directly stimulates SMC proliferation in vitro via a direct dose-response effect. In vivo low shear stress accelerates IH proportional to vWF expression. This could occur under intact endothelium without platelet activation and platelet-derived growth factor release. In effect, control of IH may entail modulation of vWF expression.

Radiation therapy combined with photofrin or 5-ALA: effect on Lewis sarcoma tumor lines implanted in mice. Preliminary results.

AIMS AND BACKGROUND: Ionizing irradiation is a well-established therapeutic modality for cancer. Photodynamic therapy (PDT), especially with 5-ALA and Photofrin, is highly effective in some tumor types. Chemical modifiers, so-called radiosensitizers, are used in order to increase the efficacy of radiotherapy. Most of the known and routinely used radiosensitizers are not tumor selective, so that the normal tissue reaction toxicity is also increased. In the present study we investigated whether a porphyrin derivative that is currently used as a tumor-photosensitizing agent in photodynamic therapy (PDT) may also act as a tumor-specific radiosensitizer. MATERIALS AND METHODS: For our investigation we used Balb/c mice implanted with Lewis sarcoma and irradiated with 3 Gy combined with injection of 5-ALA or Photofrin at various concentrations before irradiation. RESULTS: 5-ALA had no effect as a radiosensitizer at any of the concentrations examined. Photofrin at a concentration of 5 mg/kg proved to be a chemical modifier of ionizing radiation, delaying tumor growth and reducing the overall tumor volume by about 50% after six days. CONCLUSION: Photofrin has marked efficacy as a radiosensitizer and can be used in the future as a selective tumor radiosensitizer.