Particular challenges exist for science education in the developing world, where limited resources require curricula designed to balance state-of-the-art knowledge with practical and political considerations in region-specific contexts. Project-based biology teaching is especially difficult to execute due to high infrastructural costs and limited teacher training. Here, we report the results of implementing short, challenging, and low-cost biology courses to high school and college students in Bolivia, designed and taught in collaboration between scientists from developed nations and local science instructors. We find our approach to be effective at transmitting advanced topics in disease modeling, microscopy, genome engineering, neuroscience, microbiology, and regenerative biology. We find that student learning through this approach was not significantly affected by their background, education level, socioeconomic status, or initial interest in the course. Moreover, participants reported a heightened interest in pursuing scientific careers after course completion. These results demonstrate efficacy of participatory learning in a developing nation, and suggest that similar techniques could drive scientific engagement in other developing economies.

Cutaneous T-cell Lymphoma (CTCL) is a rare non-Hodgkin's lymphoma that can affect the skin, blood, and lymph nodes, and can metastasize at late stages. Novel therapies that target all affected disease compartments and provide longer lasting responses while being safe are needed. One potential therapeutic target is NF-λB, a regulator of immune responses and an important participant in carcinogenesis and cancer progression. As a transcription factor, NF-λB targets genes that promote cell proliferation and survival. Constitutive or aberrant activation of NF-λB is encountered in many types of cancer, including CTCL.Recently, while analyzing gene-expression profiles of a variety of small molecule compounds that target NF-λB, we discovered the tetracycline family of antibiotics, including doxycycline, to be potent inhibitors of the NF-λB pathway. Doxycycline is well-tolerated, safe, and inexpensive; and is commonly used as an antibiotic and anti-inflammatory for the treatment a multitude of medical conditions.In our current study, we show that doxycycline induces apoptosis in a dose dependent manner in multiple different cell lines from patients with the two most common subtypes of CTCL, Mycosis Fungoides (MF) and Sézary Syndrome (SS). Similar results were found using primary CD4+ T cells from a patient with SS. Doxycycline inhibits TNF induced NF-λB activation and reduces expression of NF-λB dependent anti-apoptotic proteins, such as BCL2α. Furthermore, we have identified that doxycycline induces apoptosis through reactive oxygen species.

No abstract

Introduction: Treatment of early-stage mycosis fungoides (MF) requires safe, skin-directed therapies. Medication side effects can lead to underutilization of effective therapies. The objective of this study was to assess the use of topical triamcinolone 0.1% ointment as a means of reducing contact dermatitis associated with topical mechlorethamine/chlormethine gel for the treatment of MF. Methods: This prospective, randomized, openlabel study evaluated 28 adults with mycosis fungoides who were eligible for treatment with topical mechlorethamine/chlormethine gel from December 17, 2017 to December 23, 2020. Patients were treated for 4 months with clinical follow-up through 12 months. Patients had half of their lesions also treated with topical triamcinolone 0.1% ointment (while the other half were treated with mechlorethamine/chlormethine alone). The study was self-controlled with separate lesions in the same patient receiving each treatment arm. Treatment arms were determined by the flip of a coin. Results: Twenty-eight patients enrolled (17 men (61%) and 11 women (39%)). Demographics included 25 White, 2 African Americans, and 1 Asian patient. Twenty-five completed the 12-month follow-up. Triamcinolone 0.1% ointment led to increased tolerability of mechlorethamine/chlormethine gel but did not change the efficacy of mechlorethamine/chlormethine. There was a statistically significant 50% decrease in dermatitis (SCORD score) at month 2 in the triamcinolone-treated arm. Conclusions: Topical triamcinolone ointment is a helpful adjuvant therapy when treating patients with topical mechlorethamine/ chlormethine gel. It diminishes inflammation and does not reduce efficacy. The peak incidence of dermatitis in the study occurred in the second and third months. Trial Registration: ClinicalTrials.gov identifier, NCT03380026.

Squamous cell carcinoma (SCC) of the skin is a keratinocyte malignancy characterized by tumors presenting on sun-exposed areas with surgery being the mainstay treatment. Despite advances in targeted therapy in other skin cancers, such as basal cell carcinoma and melanoma, there have been no such advances in the treatment of SCC. This is partly due to an incomplete knowledge of the pathogenesis of SCC. We have recently identified a protein kinase C-associated kinase (PKK) as a potential tumor suppressor in SCC. We now describe a novel conditional PKK knockout mouse model, which demonstrates that PKK deficiency promotes SCC formation during chemically induced tumorigenesis. Our results further support that PKK functions as a tumor suppressor in skin keratinocytes and is important in the pathogenesis of SCC of the skin. We further define the interactions of keratinocyte PKK with TP63 and NF-κB signaling, highlighting the importance of this protein as a tumor suppressor in SCC development.

We aimed to assess the long-term effects and safety of RTX for the treatment of pemphigus in the Chinese population. In this retrospective study, 74 pemphigus patients treated with RTX from February 2008 to December 2018 and followed up were included and analyzed. Lymphoma protocol (LP, 375mg/m 2 per week for 4 weeks) or rheumatoid arthritis protocol (RAP, 1000mg on the 1 st and 15 th day) was used as RTX protocol. The median follow-up duration was 26.1 months. CR rate was 66.2% and the median time to achieve CR was 11.0 months. Six patients received RTX as first-line treatment and all achieved CR, while the CR rate of other patients was 63.2%. Thirteen (26.5%) in 49 CR patients relapsed. The median relapse time was 12.3 months. No significant effect of RTX protocol on CR rate (P ¼ 0.016) and relapse rate (P ¼ 0.907) was observed, but RAP protocol had a shorter time to achieve CR (11.8 months vs 6.8 months, P ¼ 0.016). In baseline and during follow-up, levels of antidesmoglein autoantibodies, CD19 + B cells, CD4 + T cells, CD8 + T cells and immunoglobulins were collected and adverse events were recorded. Autoantibody level was found to change with the disease conditions. Fifteen severe adverse events (SAE) occurred in 13 (17.6%) patients. The most common SAE was pulmonary infection (13.5%, 10/74) with the median time of 64.5 days from RTX treatment to events. In those patients, 9 (90.0%) patients were with lower IgM level than normal limit. Three patients (4.1%) died because of severe pulmonary infections within 3 months. They were all evaluated as immunosuppressed at baseline. This first long-term research suggests that RTX is an effective treatment for pemphigus with a high CR rate in the Chinese population. Patients taking RTX as first-line treatment rather than nonfirst line treatment may be more likely to achieve CR. Pulmonary infection during treatment could be fatal and worthy of attention.

Oral and laryngeal cutaneous T-cell lymphoma (CTCL) is rare and usually associated with poor prognosis. Here, we discuss 2 cases of oral CTCL that developed in heavily pretreated patients and provide a review of the literature. The first case is of a 46-year-old African American male with rapidly progressive disease, presenting with a lesion on his hard palate 6 months after being diagnosed with a CD4+CD8+ CTCL. His cutaneous disease was widespread with tumors on >80% of his body surface area. Unfortunately, the patient died 2 ½ years after his CTCL diagnosis and 7 months after developing the oral CTCL lesion. The second case is of a 38-year-old African American male with stage IIb CD3+CD4+CD30+ mycosis fungoides (MF), who developed a tumor on the hard palate 6 months after diagnosis. He received palliative radiation to the oral lesion and multiple lines of systemic therapy for pulmonary, laryngeal, esophageal, and gastric involvement. Biopsy of the gastric lesions showed a CD30+ T-cell lymphoma with the same clonal peak as in his skin but with large cell transformation. Brentuximab vendoin was started, and the patient is now in complete remission, 30 months later. From the 76 cases of oral CTCL that have been reported in the English language, six were of transformed MF. The most common sites affected were the tongue and palate, and the most common presentation were erythematous or ulcerated tumors, plaques, or nodules associated with dysphagia and pain. Oral CTCL typically occurs years after the initial diagnosis of CTCL and portend a poor prognosis with an average survival of just over 1 year after development of oral lesions.

Immunology is typically first encountered by students in advanced college or graduate courses. Additional challenges to teaching immunology exist in the developing world, where limited resources require curricula balancing state-of-the-art knowledge with region-specific practical considerations. Project-based teaching is especially difficult to execute due to lack of infrastructure and teacher training. Here, we report the results of implementing short hands-on low-cost microbiology and immunology courses for high school and college students in Bolivia. This initiative, “Clubes de Ciencia Bolivia”, brings graduate students and postdoctoral fellows from research institutions in developed nations to teach weeklong intensive courses in Bolivia. These courses (“clubes”) feature project-based and active learning components and are designed and taught with local Bolivian science instructors. Our approach was effective at transmitting concepts in microbiology and immunology, as measured by subject-specific test scores before and after course completion. Importantly, student learning was not significantly affected by their background, education level, socioeconomic status, or initial interest in the specific course taken. Moreover, participants reported a heightened interest in scientific careers after course completion. Strikingly, participants scored higher in subject-specific tests than Bolivian college students who had taken related semester-long college courses. Altogether, these data indicate that participatory learning for immunology in a developing nation can be used to effectively transmit knowledge. Similar approaches are likely to drive scientific engagement in other developing economies.