Strategies for targeting and remodeling tumor microenvironment / 药学学报

Tumor microenvironment (TME) is composed of abnormal tumor vasculature, extracellular matrix components, endothelial cells, pericytes, tumor associated fibroblasts, smooth muscle cells and immune cells, which is characterized by hypoxia, acidosis and high interstitial fluid pressure. Hypoxia and acidosis within the TME trigger an adjustment of the extracellular matrix (ECM), a response from neighbor stromal cells (e.g., fibroblasts) and immune cells (lymphocytes and macrophages), inducing tumor growth, angiogenesis, and ultimately, resulting in metastasis. What's more, the components of TME including abnormal tumor vasculature, rich composition of the ECM, and abundant stroma cells impair tumoral distribution and penetration of the drugs. At the same time, this stromal microenvironment plays a vital role in creating an immunosuppressive environment.Over the past years, more and more researches focus on targeting and remolding TME to improve therapeutic effects against tumors. Herein, we reviewed current strategies developed to target and remodel TME, including modulating tumor hypoxia, tumor vasculature, tumor associated fibroblasts, extracellular matrix components, tumor associated macrophage phenotypes and dendritic cells. Also, potential problems and future directions are pointed out in this review.

Drugs and drug delivery strategies for treatment of pulmonary arterial hypertension / 药学学报

Pulmonary arterial hypertension (PAH), also named as a cancer of cardiovascular disease, is a rare disease and has complicated pathogenesis. Recently, there are more understandings of PAH pathogeneses. According to the pathogenesis and active pathways, the clinically used drugs are classified into several groups incluidng prostacyclin analogues and prostacyclin receptor agonists, endothelin receptor antagonists, phosphodiesterase-5 inhibitors, soluble guanylate cyclase inhibitors, etc. To elevate the efficacy of the drugs, numerous drug delivery systems are developed. This review mainly summarized the pathological mechanism of PAH, drugs and drug delivery approaches in the treatment of PAH.

Research & development and evaluation of oral films / 中国中药杂志

Oral film is a new type of oral preparation. Due to portability, simple preparation process and good clinical compliance, oral films have become the focus of novel drug delivery system in recent years. Meanwhile, oral films have been gradually used in the development of Chinese medicine preparations. According to the application and approval situation of different types of oral films both at home and abroad in recent years, their research and development status was analyzed, including the basic concept, formulation, manufacturing process and quality control, as well as related progress and development prospects of oral films applied in traditional Chinese medicine. Some suggestions on the technical evaluation of oral films were put forward by considering specific requirements from regulatory agencies. This paper could provide some references for the development and evaluation of oral films. Due to the complexity of the drug substances and the particularity of the drug product, the development and application of oral films in traditional Chinese medicine are still faced with opportunity and challenges.

Consumption of hydrogen-rich water protects against ferric nitrilotriacetate-induced nephrotoxicity and early tumor promotional events in rats.

The aim of this work was to test whether consumption with hydrogen-rich water (HW) alleviated renal injury and inhibited early tumor promotional events in Ferric nitrilotriacetate (Fe-NTA)-treated rats. Rats were injected with Fe-NTA solution (7.5mg Fe/kg body weight) intraperitoneally to induce renal injury and simultaneously treated with HW (1.3 ± 0.2mg/l). We found that consumption with HW ameliorated Fe-NTA-induced renal injuries including suppressing elevation of serum creatinine and blood urea nitrogen and inhibited early tumor promotional events including decreasing ornithine decarboxylase activity and incorporation of [3H]thymidine into renal DNA. Consumption with HW suppressed Fe-NTA-induced oxidative stress through decreasing formation of lipid peroxidation and peroxynitrite and activities of NADPH oxidase and xanthine oxidase, increasing activity of catalase, and restoring mitochondrial function in kidneys. Consumption with HW suppressed Fe-NTA-induced inflammation marked by reduced NF-κB, IL-6, and MCP-1 expression and macrophage accumulating in kidneys. In addition, consumption with HW suppressed VEGF expression, STAT3 phosphorylation and PCNA expression in kidneys of Fe-NTA-treated rats. Consumption with HW decreased the incidence of renal cell carcinoma and suppressed tumor growth in Fe-NTA-treated in rats. In conclusion, drinking with HW attenuated Fe-NTA-induced renal injury and inhibited early tumor promotional events in rats.

[Double-mutated oncolytic adenovirus combined with gemcitabine for treating an orthotopic nude mouse model of bladder cancer].

OBJECTIVE: To investigate the therapeutic efficacy of double-mutated oncolytic adenovirus AxdAdB-3 in combination with gemcitabine for treating bladder cancer in an orthotopic nude mouse model. METHODS: The susceptibility to the adenovirus was evaluated in bladder cancer cell lines YTS-1, T24, 5637 and KK47, and normal cell lines HCV29 and WI38. The cells were infected with AxCAlacZ and stained with 5-bromo-4-chloro-3-indolyl-ß-galactoside (X-Gal). Immunostaining against adenoviral hexon protein was performed to determine the selective replication of AxdAdB-3 in the cancer cells. Flow cytometry was used to determine the YTS-1 cells in S phase of cell cycle after adenovirus infection. Cell viability after AxdAdB-3 and/or gemcitabine was measured by CCK-8 assay. Orthotopic bladder cancer model was established in nude mice, and the inhibitory efficacy of intravesical instillation therapy with AxdAdB-3 or/and gemcitabine was assessed. RESULTS: Gene transduction efficiency was different among the cell lines, and correlated with expression of CAR. 5637 and KK47 cells with high expression of CAR were more susceptible to the adenovirus, whereas YTS-1 and T24 cells with little CAR expression were resistant to adenoviral infection. Immunostaining showed that the expression levels of hexon protein varied among the cell lines. Normal cells infected with AxdAdB-3 expressed little hexon protein. The proportion of S-phase cells was (39 ± 3) % and (49 ± 5) % in the AxCAlacZ- and AxdAdB-3-infected bladder cancer cells, respectively. AxdAdB-3 effectively induced S-phase entry of cell cycle (P < 0.05). AxdAdB-3 combined with gemcitabine significantly inhibited the growth of bladder cancer cell lines. In vivo, the mean weight of the bladder tumors in mice treated with intravesical instillation of AxCAlacZ, gemcitabine, AxdAdB-3, and AxdAdB-3 + gemcitabine were 400.6, 126.4, 82. 0, 40.4 mg, respectively. Either AxdAdB-3 (P < 0.0001) and gemcitabine (P < 0.0001) suppressed the tumor growth in nude mice, and the combination therapy reduced tumors more effectively than either AxdAdB-3 (P < 0.0001) or gemcitabine (P < 0.0001) alone. CONCLUSIONS: Intravesical instillation therapy with AxdAdB-3 in combination with gemcitabine can effectively inhibit the orthotopic bladder cancer in nude mouse, and further relevant clinical studies are guaranteed.

[Type V phosphodiesterase inhibitor erection-provoking test with audio-visual sexual stimulation for the diagnosis of erectile dysfunction].

OBJECTIVE: To evaluate the type V phosphodiesterase (PDE-5) inhibitor erection-provoking test with audio-visual sexual stimulation in the diagnosis of erectile dysfunction. METHODS: A total of 853 out-patients diagnosed with erectile dysfunction were divided into an injury and a non-injury group. After scored on IIEF-5 questionnaires, all the patients received oral administration of PDE-5 inhibitors and, 30 minutes later, audio-visual sexual stimulation. The data on penile erection were recorded with Rigiscan Plus. RESULTS: The patients with mild, moderate and severe ED accounted for 18.8, 31.9 and 49.3% in the injury group, and 50.6, 39.8 and 9.6% in the non-injury group, with statistic differences between the two groups in the mild and severe parts (P < 0.05). The rates of conspicuous effectiveness, effectiveness, ineffectiveness and total effectiveness of the combined method were 13.0, 14.5, 72.5 and 27.5% in the injury group, but 55.7, 20.7, 23.6 and 76.4% in the non-injury group, with significant differences (P < 0.05). CONCLUSION: The PDE-5 inhibitor erection-provoking test with audio-visual sexual stimulation is a simple, practical, safe and effective method for the differentiation of organic from psychological erectile dysfunction.

[Deep sarcoma of the penis: a report of 2 cases and review of the literature].

OBJECTIVE: To investigate the clinical characteristics, diagnosis, treatment and prognosis of deep sarcoma of the penis. METHODS: The pathological and clinical data of 2 cases of deep sarcoma of the penis were analyzed retrospectively and the literature reviewed. RESULTS: Both of the cases were treated by total penectomy. Epithelioid angiosarcoma of the penis was confirmed by postoperative pathology in one patient, who died of pulmonary metastasis in the eighth month after the operation; and epithelioid sarcoma of the penis was confirmed in the other, who died of brain metastasis in the second month after the operation. CONCLUSION: Deep sarcoma of the penis is rare but can be diagnosed pathologically. Total penectomy is the main option for its treatment. Node dissection, with poor prognosis, is not recommended unless adenopathy is palpable.

Surgical treatment of a rare case of penile squamous cell carcinoma in a 65-year-old man.

Penile squamous cell carcinoma has been commonly reported in the past decades. We describe a rare case of a huge squamous cell carcinoma of the penis in a 65-year-old patient with a 4-year history of tumor growth, for which total penectomy, perineal urethrostomy and bilateral inguinal lymphadenectomy were carried out. We suggest that aggressive surgical intervention should be recommended for those with well-differentiated penile carcinoma regardless of the size of the tumor.

Effects of 2-n-nonyl-1,3-dioxolane as an enhanceron transdermal absorption of Salvia miltiorrhiza gel / 中国中药杂志

<p><b>OBJECTIVE</b>To choose the most suitable concentration of 2-n-nonyl-1,3-dioxolane as a penetration enhancer in tanshinone gel preparation.</p><p><b>METHOD</b>In vitro, transdermal absorption was studied using improved Frans equipment and rats skin. Tanshinone II A was tested by HPLC.</p><p><b>RESULT</b>The 4.0% concentration of 2-n-nonyl-1,3-dioxolane enhanced the transdermal absorption significantly in the preparation.</p><p><b>CONCLUSION</b>2-n-nonyl-1,3-dioxolane was a new effective permeaton enhancer.</p>

[Observation of safety and efficacy of tadalafil for men with erectile dysfunction].

OBJECTIVE: To observe the safety and efficacy of tadalafil in the treatment of erectile dysfunction in clinical research. METHODS: Eighty patients with ED, before and after 20 mg tadalafil administered orally, received respectively the rigiscan examination with aural and visual sexual stimulation at the same time, and then Bphallic circumference variation, stiffness index, duration were compared before and after the treatment. RESULTS: Phallic stiffness index, duration revealed a statistically (P < 0.05) obvious improvement before and after the treatment for all patients. A significant difference (P < 0.01) on the phallic stiffness index, duration were found between the patients with psychogenic ED and others with organic or mixed ED after the treatment. Overall satisfaction with tadalafil was 82.5%. There was an obvious difference on the curative rates between the patients with psychogenic ED (92.3%) and others with organic ED (68.7%) or mixed ED (58.3%). All adverse events (11 cases of headache and dizziness, 8 cases of digestive canal unwell, 5 cases of flushing, 2 cases of back muscle pain) associated with tadalafil were mild and recovered without any treatment. CONCLUSION: Tadalafil improves erectile function significantly in most patients. Adverse reactions are generally transient and mild to moderate in nature.