Significant response to apatinib monotherapy in heavily pretreated advanced HER2-positive breast cancer: a case report and literature review.

Although HER2-targeted therapy has been shown to prolong the survival of patients with HER2-positive breast cancer, most patients eventually progress due to drug resistance. Novel treatment options are urgently needed to overcome resistance to HER2-targeted therapy. The VEGF/VEGFR (Vascular endothelial growth factor and its receptors) pathway is essential in tumor angiogenesis, which may be a promising target in HER2-positive breast cancer providing a rationale for the use of tyrosine kinase inhibitors (TKIs) targeting VEGFR. Here, we present a case of a heavily pretreated advanced breast cancer patient who did not respond to HER2-targeted therapy and developed resistance to multiple lines of HER2-targeted treatment. The patient was treated with apatinib at a dose of 500 mg daily, and obtained partial remission (PR) with a progression-free-stage (PFS) of 6 months. Our case indicates that apatinib might have anti-tumor activity in patients with HER2-positive breast cancer with HER2-targeted resistance. This case is of value which may provide new insights into strategies for HER2-targeted therapy resistance options in the clinic.

Prevalence and risk factors of intestinal parasitism among two indigenous sub-ethnic groups in Peninsular Malaysia.

BACKGROUND: Intestinal parasitic infections (IPIs) among indigenous people have been widely documented in Malaysia, however, the prevalence of these infections remains high. In the past, most studies have focused on specific species of parasites but polyparasitism has received limited attention. In addition, epidemiology studies on indigenous people tend to consider them as a homogenous group, whereas in reality different sub-ethnic groups have different cultural and living practices. Variations in living habits such as personal hygiene practices may predispose different groups to different parasitic infections. To better understand prevalence and risk factors of intestinal parasitism among different sub-ethnic groups, the present study was conducted among two sub-ethnic groups of indigenous people (Temuan and Mah Meri) residing in Selangor state, Malaysia. METHODS: A cross-sectional study that focused on two distinct sub-ethnic groups was carried out from February to September 2014. Faecal samples were collected from 186 participants and examined using the formalin-ether sedimentation technique. A molecular approach was adopted to conduct a genetic characterisation of the parasites. Additionally, questionnaires were administered to obtain information on the demographics, socio-economic backgrounds and behavioural risks relating to the participants, as well as information about their environments. Statistical analyses (i.e. binary and multivariate logistic regression analyses) were performed to measure risk factors. RESULTS: For Temuan communities, trichuriasis (64.2 %) was the most common infection found, preceding hookworm infection (34 %), ascariasis (7.5 %), giardiasis (14.2 %) and amoebiasis (7.5 %). As for the Mah Meri communities, trichuriasis (77.5 %) prevailed over ascariasis (21.3 %), hookworm (15 %), giardiasis (7.5 %) and amoebiasis (3.8 %). Significant differences in proportions of trichuriasis, ascariasis and hookworm infections were observed between the Temuan and Mah Meri sub-ethnic groups. Polyparasitism was more common among the Temuan sub-ethnic group (41.5 %) compared to the Mah Meri sub-ethnic group (32.5 %), with the majority of participants harbouring two parasites concurrently (Temuan: 33 %, Mah Meri: 20 %). Trichuris trichiura and Ascaris lumbricoides co-infections were most prevalent (10 %) among the Mah Meri communities, while a co-infection of T. trichiura with hookworm (19.8 %) was most common among the Temuan communities. Multivariate analyses showed that being unemployed, having a large family and drinking unboiled water were found to be significantly associated with intestinal parasitism. CONCLUSION: The present study highlights substantial polyparasitism and risk factors for infections in the Temuan and Mah Meri sub-ethnic groups. The high prevalence of IPIs among these two sub-ethnic groups indicates that parasitic infections are important health issues in these communities. Hence, it is imperative to implement sound intervention strategies such as periodic preventive chemotherapy coupled with health education in order to reduce and eradicate these infections.

Effect of ethnicity and socioeconomic variation to the gut microbiota composition among pre-adolescent in Malaysia.

Gut microbiota plays an important role in mammalian host metabolism and physiological functions. The functions are particularly important in young children where rapid mental and physical developments are taking place. Nevertheless, little is known about the gut microbiome and the factors that contribute to microbial variation in the gut of South East Asian children. Here, we compared the gut bacterial richness and composition of pre-adolescence in Northern Malaysia. Our subjects covered three distinct ethnic groups with relatively narrow range of socioeconomic discrepancy. These included the Malays (n = 24), Chinese (n = 17) and the Orang Asli (indigenous) (n = 20). Our results suggested a strong ethnicity and socioeconomic-linked bacterial diversity. Highest bacterial diversity was detected from the economically deprived indigenous children while the lowest diversity was recorded from the relatively wealthy Chinese children. In addition, predicted functional metagenome profiling suggested an over-representation of pathways pertinent to bacterial colonisation and chemotaxis in the former while the latter exhibited enriched gene pathways related to sugar metabolism.

Clinical Analysis of Treatment and Prognosis of Patients with Pain Caused by Malignant Bone Metastasis / 中国医科大学学报

Objective To analyze the clinical features,therapeutic effect and prognosis in patients with bone pain induced by malignant bone me?tastasis as well as the rationality of analgesic application,so as to improve the level of diagnosis and treatment for metastatic bone pain. Methods Totally 123 patients with pain due to malignant bone metastasis received antitumor therapy and analgesic therapy based on standardized three?step guidelines. Their clinical characteristics were retrospectively analyzed. Results The total pain relief rate was 85.4%and the pain was significantly relieved(P<0.05). The DUI value of each narcotic agent was close to 1 and the application of narcotic agents tended to be rational. The Kaplan?Meier survival analysis showed that patients with moderate pain had longer survival time than those with severe pain(P=0.015). The survival rate of patients with significant pain relief after treatment was higher than those unrelieved(P=0.021). The survival rate of patients without visceral me?tastasis was higher than those with visceral metastasis(P=0.000). The COX multivariate analysis indicated that the pain intensity and visceral me?tastasis were independent risk factors influencing patient prognosis. Conclusion Standard treatment can improve symptoms in most patients with bone metastasis and prolong survival time. Opioids have satisfactory analgesic effect for moderate to severe pain and the adverse reactions can be tol?erated.

Enterobius vermicularis salpingitis seen in the setting of ectopic pregnancy in a Malaysian patient.

We report a rare and unusual case of invasive Enterobius vermicularis infection in a fallopian tube. The patient was a 23-year-old Malaysian woman who presented with suprapubic pain and vaginal bleeding. A clinical diagnosis of ruptured right ovarian ectopic pregnancy was made. She underwent a laparotomy with a right salpingo-oophorectomy. Histopathological examination of the right fallopian tube showed eggs and adult remnants of E. vermicularis, and the results were confirmed using PCR and DNA sequencing.

E3 ubiquitin ligase Cbl-b potentiates the apoptotic action of arsenic trioxide by inhibiting the PI3K/Akt pathway

Arsenic trioxide (ATO) is a strong inducer of apoptosis in malignant hematological cells. Inducible phosphatidyl inositol 3 kinase (PI3K)-Akt activation promotes resistance to ATO. In the present study, we evaluated whether E3 ubiquitin ligase Cbl-b, a negative regulator of PI3K activation, is involved in the action of ATO. The effect of ATO on cell viability was measured by the Trypan blue exclusion assay or by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was determined by flow cytometry and protein expression was assayed by Western blotting. ATO decreased the viability of HL60 cells and induced cellular apoptosis, which was accompanied by transient activation of Akt. The PI3K/Akt inhibitor, LY294002, significantly increased ATO-induced apoptosis (P < 0.05). In addition, ATO up-regulated the expression of Cbl-b proteins. Furthermore, ATO inhibited cell viability with an IC50 of 18.54 μM at 24 h in rat basophilic leukemia-2H3 cells. ATO induced cellular apoptosis with transient activation of Akt and Cbl-b was also up-regulated. Rat basophilic leukemia-2H3 cells transfected with a dominant negative (DN) Cbl-b mutation showed overexpression of Cbl-b (DN) and enhanced Akt activation. Compared with cells transfected with vector, ATO-induced apoptosis was decreased and G2/M phase cells were increased at the same concentration (P < 0.05). The PI3K/Akt inhibitor, LY294002, re-sensitized Cbl-b (DN) overexpressing cells to ATO and reversed G2/M arrest (P < 0.05). Taken together, these results suggest that Cbl-b potentiates the apoptotic action of ATO by inhibition of the PI3K/Akt pathway.

E3 ubiquitin ligase Cbl-b potentiates the apoptotic action of arsenic trioxide by inhibiting the PI3K/Akt pathway.

Arsenic trioxide (ATO) is a strong inducer of apoptosis in malignant hematological cells. Inducible phosphatidyl inositol 3 kinase (PI3K)-Akt activation promotes resistance to ATO. In the present study, we evaluated whether E3 ubiquitin ligase Cbl-b, a negative regulator of PI3K activation, is involved in the action of ATO. The effect of ATO on cell viability was measured by the Trypan blue exclusion assay or by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was determined by flow cytometry and protein expression was assayed by Western blotting. ATO decreased the viability of HL60 cells and induced cellular apoptosis, which was accompanied by transient activation of Akt. The PI3K/Akt inhibitor, LY294002, significantly increased ATO-induced apoptosis (P < 0.05). In addition, ATO up-regulated the expression of Cbl-b proteins. Furthermore, ATO inhibited cell viability with an IC50 of 18.54 µM at 24 h in rat basophilic leukemia-2H3 cells. ATO induced cellular apoptosis with transient activation of Akt and Cbl-b was also up-regulated. Rat basophilic leukemia-2H3 cells transfected with a dominant negative (DN) Cbl-b mutation showed overexpression of Cbl-b (DN) and enhanced Akt activation. Compared with cells transfected with vector, ATO-induced apoptosis was decreased and G2/M phase cells were increased at the same concentration (P < 0.05). The PI3K/Akt inhibitor, LY294002, re-sensitized Cbl-b (DN) overexpressing cells to ATO and reversed G2/M arrest (P < 0.05). Taken together, these results suggest that Cbl-b potentiates the apoptotic action of ATO by inhibition of the PI3K/Akt pathway.

Diagnostic value of determination of CEA, CA125, CA153 and CA199 assay in pleural fluid for lung cancer / 中国肺癌杂志

<p><b>BACKGROUND</b>To study the diagnostic value of detection of carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), cancer antigen 153 (CA153) and cancer antigen 199 (CA199) in pleural fluid samples for lung cancer.</p><p><b>METHODS</b>Immunoprotein quantity of CEA, CA125, CA153 and CA199 was analyzed in pleural fluid and serum from patients with lung cancer (52 cases) and in pleural fluid from non cancerous patients (50 cases) by chemiluminescence.</p><p><b>RESULTS</b>The levels of CEA, CA125, CA153 and CA199 in pleural fluid of patients with lung cancer were significantly higher than those of non cancerous patients ( P < 0.01 or P < 0.05). In lung cancer patients, the levels of CEA, CA125, CA153 and CA199 in pleural fluid were obviously higher than those in serum ( P < 0.01 or P < 0.05). The sensitivity and the specificity of CEA+CA199 were 96.2% and 96.0%, respectively.</p><p><b>CONCLUSIONS</b>Detection of CEA, CA125, CA153 and CA199 in pleural fluid might be helpful for diagnosing lung cancer, and the optimal combination for assay is CEA+CA199.</p>