Diagnosis and treatment of tuberculosis in adults with HIV.

Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), continues to pose a major public health problem and is the leading cause of mortality in people infected with human immunodeficiency virus (HIV). HIV infection greatly increases the risk of developing TB even before CD4+ T-cell counts decrease. Co-infection provides reciprocal advantages to both pathogens and leads to acceleration of both diseases. In HIV-coinfected persons, the diagnosis and treatment of tuberculosis are particularly challenging. Intensifying integration of HIV and tuberculosis control programmes has an impact on reducing diagnostic delays, increasing early case detection, providing prompt treatment onset, and ultimately reducing transmission. In this Review, we describe our current understanding of how these two pathogens interact with each other, new sensitive rapid assays for TB, several new prevention methods, new drugs and regimens.

Allogenic mouse cell vaccine inhibits lung cancer progression by inhibiting angiogenesis.

Aim: This research investigated the therapeutic effect of an allogeneic mouse brain microvascular endothelial cell vaccine on lung cancer and further elucidated its potential anti-angiogenic mechanism. Materials & methods: The immune effect of the allogeneic bEnd.3 vaccine and DC vaccine loaded with bEnd.3 antigen on the subcutaneous transplantation of Lewis lung cancer (LLC) was assessed by ELISA, the CCK test and the CTL killing test. The mechanism was preliminarily revealed by immunohistochemistry and immunoblot analysis. Results: This study revealed that tumor volume was decreased (p < .01) and the survival was prolonged significantly (p < .05) by the bEnd.3 vaccine in subcutaneous LLC transplantation in the vaccine prevention group. In contrast, both tumor volume in the serum therapeutic group and survival of bEnd.3 vaccine were not significantly different from those of the control group (p > .05). Importantly, tumor volume and survival of the T lymphocyte therapeutic group were decreased and prolonged (p < .05). In addition, both tumor volume and survival of DC vaccine loaded with bEnd.3 in the vaccine prevention group were decreased and prolonged significantly (p < .01). Furthermore, bEnd.3 vaccine and DC vaccine loaded with bEnd.3 both produced the activity of killing bEnd.3 target cells in vitro.The reason may induce the immune mice to produce anti-VEGFR-II, anti-endoglin and anti-integrin αν antibodies to have an anti-angiogenesis function. Conclusion: The allogeneic mouse bEnd.3 cell vaccine can block angiogenesis and prevent the development of lung cancer transplantation tumors.

Intravenous analgesia with ultra-high-dose morphine for the treatment of headache and successful withdrawal of morphine: A case report and literature review.

RATIONALE: Pain is the fifth vital sign of human beings. Morphine is the first choice for relieving moderate to severe cancer pain. Most of the previous studies merely focused on the analgesic effect of high-dose or ultra-high-dose morphine in patients with advanced cancers but did not report any cases related to successful morphine withdrawal. PATIENT CONCERNS: A 42-year-old woman was admitted to our hospital in March 2019. DIAGNOSIS: She was diagnosed with progressive aggravation of headache for 1 month, which was meningeal metastasis of lung cancer. INTERVENTIONS: Symptomatic treatments like dehydration, hormone, intrathecal injection chemotherapy and an increased dose of osimertinib to 160 mg/day were applied but showed poor curative effects. The patient refused whole-brain radiotherapy. Pain intensity level was re-evaluated and the patient scored 9 based on numerical rating scale, which suggested that the patient suffered from severer cancerous pain. Thus, the patient started to receive morphine for treating headache. OUTCOMES: The patient's headache was alleviated after receiving high-dose morphine treatment, and she continued to undergo anti-cancer treatment. After tumor remission, the patient's morphine dose gradually decreased and eventually stopped, without any withdrawal symptoms. In addition, the quality of life of the patient was greatly improved with performance status scored 2 and limb muscle strength increased from Grade 2 to Grade 5. LESSONS: For patients with advanced cancers, the application of ultra-high-dose morphine may significantly relieve cancerous pain, improve survival and quality of life, and overcome their fear for death and desperation, which contributes to the establishment of a basis for subsequent anticancer treatments. Thus, timely effective pain management and routine anticancer treatments are the key to addressing the cancer pain problem.

MiR-1260b inhibitor enhances the chemosensitivity of colorectal cancer cells to fluorouracil by targeting PDCD4/IGF1.

Colorectal cancer (CRC) is the most common malignant tumor type and has become resistant to 5-fluorouracil (5-FU) in recent decades, which is one of the most popular therapies. Recently, microRNA (miRNA or miR) has been investigated as a potential therapeutic strategy for CRC. However, there has been little investigation of the underlying mechanism of the association between expression of miRNA and chemosensitivity. The present study aimed to investigate the effect of miR-1260b inhibitor on CRC cells, and their chemosensitivity to 5-FU, by treating them with the miR-1260b inhibitor. miR-1260b inhibitor was demonstrated to significantly promote the proliferation and invasion of the CRC cell line, HCT116, and to increase the apoptotic rate. Furthermore, it was validated that programmed cell death 4 (PDCD4) was a direct target of miR-1260b inhibitor in CRC with bioinformatics tools and a luciferase assay. Western blot analysis revealed that miR-1260b inhibitor could significantly decrease PDCD4 expression, and downregulate the expression of phosphorylated-Akt (p-Akt) and phosphorylated-extracellular-signal-regulated kinase (p-ERK). In conclusion, it was confirmed that the anti-tumor effect of the miR-1260b inhibitor was conducted by blocking the phosphorylated 3-kinase/Akt pathway as dysregulated protein expression induced by miR-1260b inhibitor was rescued by insulin-like growth factor. Notably, miR-1260b inhibitor could significantly enhanced the chemoresponse of HCT116 cells to 5-FU via reduced proliferation, increased apoptosis, and downregulation of PDCD4, p-Akt and p-ERK protein expression. In summary, the present study may provide a novel direction for future clinical therapy to enhance the chemosensitivity of tumor cells.

Efficacy for lung metastasis induced by the allogeneic bEnd3 vaccine in mice.

BACKGROUND: The mouse brain microvascular endothelial cell line bEnd.3 was used to develop a vaccine and its anti-tumor effect on lung metastases was observed in immunized mice. METHODS: Mouse bEnd.3 cells cultured in-vitro and then fixed with glutaraldehyde was used to immunize mice; mice were challenged with the metastatic cancer cell line U14, and changes in metastatic cancer tissues were observed through hematoxylin and eosin staining. Carboxyfluorescein succinimidyl amino ester (CSFE) and propidium iodide (PI) were used to detect cytotoxic activity of spleen T lymphocytes; the ratio of CD3+ and CD8+ T-cell sub-sets was determined by flow cytometry. Enzyme-linked immunosorbent assay (ELISA), immunocytochemistry and immunoblot were used to examine the specific response of the antisera of immunized mice. RESULTS: The number of metastatic nodules in bEnd.3 and human umbilical vein endothelial cell (HUVEC) vaccine groups was less than NIH3T3 vaccine group and phosphate buffered saline (PBS) control group. The bEnd.3-induced and HUVEC-induced cytotoxic T-lymphocytes (CTLs) showed significant lytic activity against bEnd.3 and HUVEC target cells, while the antisera of mice in bEnd.3 and HUVEC vaccine groups showed specific immune responses to membrane proteins and inhibited target cell proliferation in-vitro. Immunoblot results showed specific bands at 180KD and 220KD in bEnd.3 and at 130 kD and 220 kD in HUVEC lysates. CONCLUSIONS: Allogeneic bEnd.3 vaccine induced an active and specific immune response to tumor vascular endothelial cells that resulted in production of antibodies against the proliferation antigens VEGF-R II, integrin, Endog etc. Immunization with this vaccine inhibited lung metastasis of cervical cancer U14 cells and prolonged the survival of these mice.