Serum testosterone level as possible predictive marker in androgen receptor axis-targeting agents and taxane chemotherapies for castration-resistant prostate cancer

Purpose

Currently, several therapeutic options for castration-resistant prostate cancer (CRPC) are available, for which predictive biomarkers have not been established. Therefore, we aimed to reveal the association between pretreatment serum testosterone level and antitumor outcomes when treated with androgen receptor axis-targeting agents and taxane chemotherapies for CRPC.

The effect of supragingival plaque control on the subgingival microbiota in subjects with periodontal disease

The present investigation was performed to study the effect on the subgingival microbiota, of a plaque control program which included meticulous oral hygiene instruction, supragingival scaling and professional monitoring during a 2 year period. 300 subjects were examined for periodontal disease and monitored for 2 years without treatment. After the 2 year examination, 80 subjects were invited to participate in a treatment program intended to improve the standard of their self-performed plaque control. 40 of the invitees had a gingivitis and only minor attachment loss, while 40 subjects had moderate signs of periodontitis. 62 subjects volunteered for this treatment. 23 of the volunteers (Group AB) had several sites with deep pockets (> 4 mm). 39 of the volunteers had gingivitis but shallow pockets only (Group C). Group AB contributed 31 shallow pocket sites (A-sites) and 40 deep pocket sites (B-sites), while Group C contributed 63 shallow sites (C-sites). After the clinical examination, samples of the subgingival microbiota were harvested from the 134 A, B and C sites. The 62 subjects were enrolled in a supervised oral hygiene program. Supragingival scaling was carried out. Oral hygiene instruction was provided and repeated on an individual need basis so that all subjects reached and maintained a supragingival plaque score which was < 20%. 24 months after the year 2 examination, the 62 subjects were examined again using both clinical and microbiological examination procedures. The findings demonstrated that carefully performed supragingival plaque control changed the quantity and the composition of the supragingival microbiota.(ABSTRACT TRUNCATED AT 250 WORDS)     

ASO Author Reflections: Safety and Curability of Lymphadenectomy for Salvage Esophagectomy

Annals of Surgical Oncology -     

SPan-1 Is a Useful Prognostic Marker for Patients with Stage IV Gastric Cancer Who Underwent Palliative Gastrectomy: A Retrospective Multivariate Study

Background

We retrospectively investigated prognostic factors to be used in selecting the patients with stage IV gastric cancer (GC) who have an unfavorable prognosis after palliative gastrectomy.

Methods

A total of 146 GC patients at stage IV who had undergone palliative gastrectomy were enrolled. Various clinicopathological parameters were evaluated for prognosis.

Results

Surgical morbidity and hospital mortality occurred in 35 (23.9 %) and 4 (2.7 %) patients, respectively. The overall 5-year survival rate and the median survival time were 11.2 % and 13.2 months, respectively. Of the 146 patients, 64 had uncomfortable symptoms associated with GC and 76 had no such symptoms. Of the 64 patients with uncomfortable symptoms, 60 (93.7 %) experienced relief of these symptoms after palliative surgery. Multivariate analysis for patients without uncomfortable symptoms associated with GC revealed that the number of incurable factors and serum SPan-1 level were independent prognostic factors.

Conclusions

Patients with stage IV GC who had multiple incurable factors and a high level of serum SPan-1 might not be candidates for palliative gastrectomy for the purpose of prognostic benefit.     

Relationship between body mass index and preoperative treatment response to aromatase inhibitor exemestane in postmenopausal patients with primary breast cancer

BackgroundSome studies have shown that high body mass index (BMI) is associated with inferior outcome after adjuvant therapy with anastrozole in breast cancer patients. We aimed to investigate predictive effect of BMI on clinical response to neoadjuvant therapy with exemestane in postmenopausal patients with primary breast cancer.Patients and methodsThe study group consisted of 109 patients from the JFMC 34-0601 neoadjuvant endocrine therapy trial. Patients were categorized into three groups according to BMI: low (BMI < 22 kg/m²), intermediate (22 ≤ BMI < 25 kg/m²) and high (BMI ≥ 25 kg/m²). Statistical analyses were performed to explore the predictive effect of BMI on clinical response.ResultsHigher BMI correlated with positive progesterone receptor status (p < 0.01) and low Ki-67 index (p = 0.03). Objective response rates (ORR) were 21.7% in low BMI, 56.0% in intermediate BMI and 60.6% in high BMI, respectively (p = 0.01). In a multivariate analysis, low BMI was an independent negative predictor of clinical response.ConclusionLow BMI was associated with a decreased ORR to neoadjuvant endocrine therapy with exemestane. Our results may suggest that the predictive effect of BMI varies according to the type of aromatase inhibitor and objective outcome.     

Therapeutic action of 5-HT3 receptor antagonists targeting peritoneal macrophages in post-operative ileus

Background and Purpose

Post-operative ileus (POI) is induced by intestinal inflammation. Here, we aimed to clarify the effects of 5-HT₃ receptor antagonists against POI.

Experimental Approach

We administered three 5-HT₃ receptor antagonists, ondansetron, tropisetron and palonosetron, to a mouse model of POI induced by surgical intestinal manipulation (IM). Immunohistochemistry, intestinal transit, inflammatory mediator mRNA expression and 5-HT content were measured. In some experiments, 5-HT₃A receptor null mice were used.

Key Results

Three 5-HT₃ receptor antagonists reduced IM-induced infiltration of inflammatory CD68-positive macrophages and myeloperoxidase-stained neutrophils. Ondansetron exhibited no anti-inflammatory actions in 5-HT₃A receptor null mice. Ondansetron inhibited expression of the chemokine CCL2, IL-1β, IL-6, TNF-α and iNOS mRNAs up-regulated by IM, and also ameliorated the delayed gastrointestinal transit. Peritoneal macrophages, but not most infiltrating monocyte-derived macrophages, expressed 5-HT₃ receptors. IM stimulation increased the 5-HT content of peritoneal lavage fluid, which up-regulated mRNA expression of proinflammatory cytokines in peritoneal macrophages. Immunohistochemical localization of 5-HT₃ receptors suggests that ondansetron suppressed expression of these mRNAs in activated peritoneal macrophages, adhering to the serosal region of the inflamed intestinal wall.

Conclusion and Implications

5-HT₃ receptor antagonists were anti-inflammatory, mainly targeting peritoneal macrophages expressing these receptors. They also restored the delayed gastrointestinal transit by IM. 5-HT₃ receptor antagonists should be therapeutically useful agents against POI.