Surgical resection plus biotherapy/chemotherapy improves survival of hepatic metastatic melanoma

AIM: To analyze the correlation of treatment method with the outcome of all the hepatic metastatic mela-noma (HMM) patients from our hospital.METHODS: There were altogether nine cases of HMM that had been treated in the PUMCH hospital during the past 25 years, from December 1984 to February 2010. All of the cases developed hepatic metastasis from primary cutaneous melanoma. A retrospective review was performed on all the cases in order to draw informative conclusion on diagnosis and treatment in correlation with the prognosis. Clinical features including symptoms, signs, blood test results, Bultrasound and computed tomography (CT) imaging characteristics, and pathological data were analyzed in each case individually. A simple comparison was made on case by case basis instead of performing statistical analysis since the case numbers are low and patients were much diversified in each item that has been analyzed. Literatures on this subject were reviewed in order to draw a safe conclusion and found to be supportive to our finding in a much broad scope. RESULTS: There are six males and three females whose ages ranged 39-74 years old with an average of 58.8. Patients were either with or without symptoms at the time of diagnosis. The liver function and tumor marker exam were normal in all but one patient. The incidence of HMM does not affect liver function and was not related to virus infection status in the liver. Most of these HMM patients were also accompanied by the metastases of other locations, including lung, abdominal cavity, and cervical lymph nodes. Ultra-sound examinations showed lesions ranging 2-12 cm in diameter, with noor low-echo peripheral areola. Doppler showed blood flow appeared inside some tumors as well as in the surrounding area. CT image demonstrated low density without uniformed lesions, characterized with calcification in periphery, and en-hanced in the arterial phase. Contrast phase showed heterogeneous enhancement, with a density higher than normal liver tissue, which was especially appar-ent at the edge. Patients were treated differently with following procedures: patients #1, #6 and #8 were operated with hepatectomy with or without removal of primary lesion, and followed by comprehensive biotherapy/chemotherapy; patient #9 received hepatectomy only; patient #2 received bacille calmette-guerin treatment only; patient #7 had Mile’s surgery but no hepatectomy; and patients #3, #4 and #5 had supportive treatment without specific measurement. The patients who had resections of metastatic lesions followed by post-operative comprehensive therapy have an average survival time of 30.7 mo, which is much longer than those did not receive surgery treatment (4.6 mo). Even for the patient receiving a resection of HMM only, the post-operative survival time was 18 mo at the time we reviewed the data. This patient and the patient #6 are still alive currently and subjected to continue following up. CONCLUSION: Surgical operation should be first choice for HMM treatment, and together with biothera-py/chemotherapy, hepatectomy is likely to bring better prognosis.

Cryomicroneedle delivery of nanogold-engineered Rhodospirillum rubrum for photochemical transformation and tumor optical biotherapy

Tumor metabolite regulation is intricately linked to cancer progression.Because lactate is a characteristic metabolite of the tumor microenvironment(TME),it supports tumor progression and drives immunosuppression.In this study,we presented a strategy for antitumor therapy by developing a nanogold-engineered Rhodospirillum rubrum(R.r-Au)that consumed lactate and produced hydrogen for optical biotherapy.We leveraged a cryogenic micromolding approach to construct a transdermal therapeutic cryomicroneedles(CryoMNs)patch integrated with R.r-Au to efficiently deliver living bacterial drugs.Our long-term storage studies revealed that the viability of R.r-Au in CryoMNs remained above 90%.We found that the CryoMNs patch was mechanically strong and could be inserted into mouse skin.In addition,it rapidly dissolved after administering bacterial drugs and did not produce by-products.Under laser irradiation,R.r-Au effectively enhanced electron transfer through Au NPs actuation into the photosynthetic system of R.rubrum and enlarged lactate consumption and hydrogen production,thus leading to an improved tumor immune activation.Our study demonstrated the potential of CryoMNs-R.r-Au patch as a minimally invasive in situ delivery approach for living bacterial drugs.This research opens up new avenues for nanoengineering bacteria to transform tumor metabolites into effective substances for tumor optical biotherapy.

Living symbiotic bacteria-involved skin dressing to combat indigenous pathogens for microbiome-based biotherapy toward atopic dermatitis

Many skin diseases,such as atopic dermatitis(AD),are featured with the dysbiosis of skin microbiota.The clinically recommended options for AD treatments suffer from poor outcomes and high side-effects,leading to severe quality-of-life impairment.To deal with this long-term challenge,we develop a living bacterial formu-lation(Hy@Rm)that integrates skin symbiotic bacteria of Roseomonas mucosa with poly(vinyl pyrrolidone),poly(vinyl alcohol)and sodium alginate into a skin dressing by virtue of the Ca^(2+)-mediated cross-linking and the freezing-thawing(F-T)cycle method.Hy@Rm dressing creates a favorable condition to not only serve as extrinsic culture harbors but also as nutrient suppliers to support R.mucosa survival in the harsh microenvi-ronment of AD sites to defeat S.aureus,which predominantly colonizes AD skins as an indigenous pathogen,mainly through the secretion of sphingolipids metabolites by R.mucosa like a therapeutics bio-factory.Mean-while,this elaborately designed skin dressing could accelerate wound healing,normalize aberrant skin char-acters,recover skin barrier functions,alleviate AD-associated immune/inflammation responses,functioning like a combinational therapy.This study offers a promising means for the topical bacteria transplant to realize effective microbe biotherapy toward the skin diseases feature with microbe milieu disorders,including but not limited to AD disease.

Recent advances of biomaterials in biotherapy

Biotherapy mainly refers to the intervention and the treatment of major diseases with biotechnologies or bio-drugs,which include gene therapy,immunotherapy(vaccines and antibodies),bone marrow transplantation and stem-cell therapy.In recent years,numerous biomaterials have emerged and were utilized in the field of biotherapy due to their biocompatibility and biodegradability.Generally,biomaterials can be classified into natural or synthetic polymers according to their source,both of which have attracted much attention.Notably,biomaterials-based non-viral gene delivery vectors in gene therapy are undergoing rapid development with the emergence of surface-modified or functionalized materials.In immunotherapy,biomaterials appear to be attractive means for enhancing the delivery efficacy and the potency of vaccines.Additionally,hydrogels and scaffolds are ideal candidates in stem-cell therapy and tissue engineering.In this review,we present an introduction of biomaterials used in above biotherapy,including gene therapy,immunotherapy,stem-cell therapy and tissue engineering.We also highlighted the biomaterials which have already entered the clinical evaluation.

Biomaterial-assisted biotherapy:A brief review of biomaterials used in drug delivery,vaccine development,gene therapy,and stem cell therapy

Biotherapy has recently become a hotspot research topic with encouraging prospects in various fields due to a wide range of treatments applications,as demonstrated in preclinical and clinical studies.However,the broad applications of biotherapy have been limited by critical challenges,including the lack of safe and efficient de-livery systems and serious side effects.Due to the unique potentials of biomaterials,such as good biocompati-bility and bioactive properties,biomaterial-assisted biotherapy has been demonstrated to be an attractive strategy.The biomaterial-based delivery systems possess sufficient packaging capacity and versatile functions,enabling a sustained and localized release of drugs at the target sites.Furthermore,the biomaterials can provide a niche with specific extracellular conditions for the proliferation,differentiation,attachment,and migration of stem cells,leading to tissue regeneration.In this review,the state-of-the-art studies on the applications of bio-materials in biotherapy,including drug delivery,vaccine development,gene therapy,and stem cell therapy,have been summarized.The challenges and an outlook of biomaterial-assisted biotherapies have also been discussed.

Advances in non-surgical management of primary liver cancer

Hepatocellular carcinoma(HCC) is the fifth most common cancer and the third most common cause of cancer-related death worldwide. There have been great improvements in the diagnosis and treatment of HCC in recent years, but the problems, including difficult diagnosis at early stage, quick progression, and poor prognosis remain unsolved. Surgical resection is the mainstay of the treatment for HCC. However, 70%-80% of HCC patients are diagnosed at an advanced stage when most are ineligible for potentially curative therapies such as surgical resection and liver transplantation. In recent years, non-surgical management for unrespectable HCC, such as percutaneous ethanol injection, percutaneous microwave coagulation therapy, percutaneous radiofrequency ablation, transcatheter arterial chemoembolization, radiotherapy, chemotherapy, biotherapy, and hormonal therapy have been developed. These therapeutic options, either alone or in combination, have been shown to control tumor growth, prolong survival time, and improve quality of life to some extent. This review covers the current status and progress of non-surgical management for HCC.

Magnetic resonance imaging may predict deep remission in patients with perianal fistulizing Crohn's disease

To evaluate the imaging course of Crohn’s disease (CD) patients with perianal fistulas on long-term maintenance anti-tumor necrosis factor (TNF)-α therapy and identify predictors of deep remission.METHODSAll patients with perianal CD treated with anti-TNF-α therapy at our tertiary care center were evaluated by magnetic resonance imaging (MRI) and clinical assessment. Two MR examinations were performed: at initiation of anti-TNF-α treatment and then at least 2 years after. Clinical assessment (remission, response and non-response) was based on Present’s criteria. Rectoscopic patterns, MRI Van Assche score, and MRI fistula activity signs (T2 signal and contrast enhancement) were collected for the two MR examinations. Fistula healing was defined as the absence of T2 hyperintensity and contrast enhancement on MRI. Deep remission was defined as the association of both clinical remission, absence of anal canal ulcers and healing on MRI. Characteristics and imaging patterns of patients with and without deep remission were compared by univariate and multivariate analyses.RESULTSForty-nine consecutive patients (31 females and 18 males) were included. They ranged in age from 14-70 years (mean, 33 years). MRI and clinical assessment were performed after a mean period of exposure to anti-TNF-α therapy of 40 ± 3.7 mo. Clinical remission, response and non-response were observed in 53.1%, 20.4%, and 26.5% of patients, respectively. Deep remission was observed in 32.7% of patients. Among the 26 patients in clinical remission, 10 had persisting inflammation of fistulas on MRI (T2 hyperintensity, n = 7; contrast enhancement, n = 10). Univariate analysis showed that deep remission was associated with the absence of rectal involvement and the absence of switch of anti-TNF-α treatment or surgery requirement. Multivariate analysis demonstrated that only the absence of rectal involvement (OR = 4.6; 95%CI: 1.03-20.5) was associated with deep remission.CONCLUSIONDeep remission is achieved in approximately one third of patients on maintenance anti-TNF-α therapy. Absence of rectal involvement is predictive of deep remission.

Liver-specific therapies for metastases of neuroendocrine pancreatic tumors

The presence or development of liver metastases in patients with neuroendocrine pancreatic tumors is the most important prognostic factor.Liver resection,transplantation and many different therapeutic approaches are discussed in this special review.

Role of Th17 cells in the pathogenesis of rheumatoid arthritis

Since early description of CD4/CD8 T cell duality, continuous discovery of functional T lymphocyte subsets and their related cytokines constitutes major progress in our understanding of the immune response. T-lymphocyte derived lymphokines and environmental cytokines are essential for both innate and antigen-specific immune responses to a wide variety of agents. Following immune battle and aggression overcome, cytokines may return against neighbored cells/organs, causing pathogenic hypersensitivity reactions, including autoimmune diseases. Due to their cytokine production, CD4+ T helper lymphocyte subsets may be considered as one the major players of the immune response. Among CD4+ T cell subsets, the identification of interleukin-17-producing cells(Th17) led to better understanding of coordinated cytokine involvement during inflammatory reactions together with the subsequent clarification of complex interactions between these mediators. In this review, we discuss Th17 cell differentiation, functions, and the role of this cell subset during rheumatoid arthritis pathogenesis together with therapeutic strategies to control these cells.

Bioinhibition of diarrhogenic Gram-positive bacterial pathogens by potential indigenous probiotics

High level infant mortality rates and onset of drug resistance has led into the possible development of indigenous probiotics as alternative bacteriotherapy in the control of infantile bacterial diarrhoea.This study was to determine the in vitro inhibitory potential of four probiotic candidates obtained from Nigerian indigenous fermented foods and beverages and from faecal specimens of healthy infants on infantile Gram-positive diarrhogenic bacterial pathogens.Potential probiotic candidates,AAOOL4,L.reuteri AAOOCH1,L.plantarum AA0025NN and L.delbrueckii AAOOT20 were assayed for in vitro bactericidal effects on diarrhogenic bacterial test strains-Bacillus cereus 25S,B.cereus 32S,B.licheniformis 26S and B.licheniformis 39S.All the test strains inoculated into an industrial infant weaning food already seeded with the probiotic strains were significantly inhibited within 96 hours.L.acidophilus AAOOL4,L.reuteri AAOOCH1,L.plantarum AAOO25NN and L.delbrueckii AAOOT20 had in vitro bactericidal effects on bacteri isolates implicated in infantile diarrhoea,indicating the probiotic potential of the candidates.

Adult Onset Still’s Disease: Articular Manifestations in Twenty Cases

The adult onset Still’s disease is a rare inflammatory pathology of unknown pathogeny. The clinical features are variable. The diagnosis is difficult since exclusion of infectious, systemic and tumoral pathologies should be done. The articular complications are frequent and can be revelatory of this pathology. The articular prognosis depends on the diagnosis delay and the treatment efficiency. Our study aims to analyze different aspects of articular manifestations complicating adult onset Still’s disease to define epidemiological, clinical and evolving characteristics of these complications. It was a cross-sectional study concerning 20 cases of adult onset Still’s disease diagnosed from 1990 to 2015 in the internal medicine A department of Charles Nicolle Hospital in Tunis, meeting Yamaguchi criteria. We identified clinical, radiological, evolving and therapeutic profile of the articular manifestations occurred in these patients. There were 13 women and 7 men. The average age was 25 years. The arthralgias were reported in all cases;while, the arthritis interested fifteen patients. A hand deformation was found in four patients. A wrist ankylosis was noted in one case and a flexion elbow in one patient. The standard articular radiographs were normal in twelve cases. The treatment associated essentially non-steroidal anti-inflammatory and/or corticosteroids and/or methotrexate. Concerning the evolving profile, the monocyclic form was present in 25% of the cases, the intermittent form in 45% and the chronic articular form in 30% of our patients. The adult onset Still’s disease is rare and heterogeneous. The articular disturbances are frequent and have various outcomes.

Afluria

全球主要的流感疫苗制造商CSL Biotherapies公司近日宣布，美国FDA已批准其产品Afluria（R）（流感病毒疫苗）上市，用于18岁以上（包括18岁）人群的主动接种，预防由A型和B型流感病毒所导致的疾病。此举标志CSL Biotherapies公司首次进军美国疫苗市场。

Recent advances in systemic lupus erythematosus and microbiota: from bench to bedside

Systemic lupus erythematosus(SLE)is a complicated autoimmune disease affecting multiple systems and organs.It is highly heterogeneous,and it preferentially affects women at childbearing age,causing worldwide social burden.The pathogenesis of SLE mostly involves genetic predisposition,epigenetic dysregulation,overactivation of the immune system,and environment factors.Human microbiome,which is mostly composed of microbiota colonized in the gut,skin,and oral cavity,provides a natural microbiome barrier against environmental risks.The past decade of research has demonstrated a strong association between microbiota and metabolic diseases or gastrointestinal diseases.However,the role of microbiota in autoimmunity remains largely unknown until recently,when the technological and methodological progress facilitates further microbiota research in SLE.In this review,the latest research about the role and mechanisms of microbiota in SLE and the advances in the development of diagnostic and therapeutic strategies based on microbiota for SLE were summarized.