Expression of cytoplasmic-domain substituted epidermal growth factor receptor inhibits tumorigenicity of EGFR-overexpressed human glioblastoma multiforme

The accumulated results of recent clinical studies have indicated that aberrant epidermal growth factor receptor (EGFR) activation due to gene amplification and/or rearrangement contributes to increased malignancy and poor prognosis in many human cancers, especially in human glioblastoma multiforme (GBM). The elevated EGFR signaling in GBM has been correlated with shorter interval to relapse and lower survival rates, even in patients treated with surgery, radiation therapy, and/or chemotherapy. Therefore, the blockade of EGFR signaling in GBM may provide an ideal alternative therapeutic strategy. In this study, two EGFR-overexpressing human GBM cell lines (i.e., DBTRG and GBM 8901) were used as a model system. We demonstrated that expression of a human EGFR (EGFRt-EGFP) chimera protein in which the cytoplasmic domain is substituted by EGFP significantly reduced the EGF-induced endogenous EGFR autophosphorylation, EGF-induced downstream extra-cellular signal-regulated kinase (ERK) and Akt signaling, and the proportion of internalized receptors in EGF stimulated cells. Furthermore, these cells' anchorage-independent growth in vitro was decreased and their tumorigenicity in vivo abrogated or strongly suppressed. Our data suggest that EGFRt-EGFP abrogates tumor growth by disrupting receptor activation via competing for EGF-like ligands, forming non-activated heterodimers with endogenous EGFR, and inhibiting the EGFR endosomal signaling by substantially diminishing receptor internalization. This treatment modality (termed 'dominant-negative EGFR therapy') and its efficacy for gliomas or other tumors are under scrutiny.     

Inhibition of NF-kappaB in cancer cells converts inflammation- induced tumor growth mediated by TNFalpha to TRAIL-mediated tumor regression

We used an experimental murine cancer metastasis model in which a colon adenocarcinoma cell line generates lung metastases, whose growth is stimulated in response to injection of bacterial lipopolysaccharide (LPS), to investigate the role of NF-kappaB in inflammation-induced tumor growth. We found that LPS-induced metastatic growth response in this model depends on both TNFalpha production by host hematopoietic cells and NF-kappaB activation in tumor cells. Inhibition of NF-kappaB in both colon and mammary carcinoma cells converts the LPS-induced growth response to LPS-induced tumor regression. The latter response is TNFalpha-independent, but depends on another member of the TNF superfamily, TRAIL, whose receptor is induced in NF-kappaB-deficient cancer cells.     

Dang-Gui-Bu-Xai-Tang modulated the immunity of tumor bearing mice

Dang-Gui-Bu-Xai-Tang (DGBXT), which includes Radix Angelicae Sinensis and Radix Astragali Membranaceus, is a traditional Chinese medicine used to modulate the lymphocyte activity of cancer patients after chemotherapy and radiotherapy. In the present study, we examined the cytotoxicity of DGBXT on transformed cells and the immunomodulating effects of DGBXT in a tumor-bearing murine model. DGBXT markedly inhibited the growth of the EJ-Ha-ras transformed LZEJ and LZEJ-C2 cells lines. Oral administration of DGBXT for three weeks significantly prevented the tumor development in mice that injected with LZEJ-C2 cells subcutaneously. Moreover, DGBXT effectively increased the population of cytotoxic T lymphocytes (CTLs) and NK cells, and down-regulated activated T helper cells (CD4+/CD25+) in spleen and tumor-draining lymph nodes (TDLN). Furthermore, DGBXT stimulated the production of tumor necrosis factor-alpha in in vitro cultured splenocytes. These results might explain the antitumor effects of DGBXT.     

An unexpected quadruplet heterotopic pregnancy after bilateral salpingectomy and replacement of three embryos

OBJECTIVE: To report a case of combined intrauterine and interstitial twin pregnancies after bilateral salpingectomy and IVF with replacement of three embryos. DESIGN: Case report. SETTING: University hospital. PATIENT(S): A 31-year-old woman known to have bilateral salpingectomy for ectopic pregnancies who underwent IVF. INTERVENTION(S): Laparotomy. MAIN OUTCOME MEASURE(S): Postoperation intrauterine monozygotic twins survival and birth. RESULT(S): After removing the interstitial monozygotic twin pregnancy, the patient had an uneventful postoperative course and delivered two healthy girls by cesarean section at 38 weeks' gestation. CONCLUSION(S): Heterotopic pregnancy can still occur in women treated by IVF after bilateral salpingectomy. The early sonography follow-up of IVF pregnancy would be of value because of the reported higher incidence of pathological pregnancies and especially monozygotic twinning.     

Comparison of total laparoscopic hysterectomy and laparoscopically assisted vaginal hysterectomy

We compare the surgical results of 60 women undergoing laparoscopically assisted vaginal hysterectomy (LAVH) and 41 having total laparoscopic hysterectomy (TLH) under the indications of uterine fibroids or adenomyosis. With similar specimen weight, TLH required longer surgery duration (140.4 vs. 115.1 min; p < 0.05) than LAVH. Among women with uteri weighing 0.05) although the TLH group had a significantly higher rate of previous abdominal surgery (57.7 vs. 20%; p < 0.05). There were no significant differences between the two groups with respect to the mean cost, length of hospital stay and rate of various complications (p > 0.05). As for sexual symptoms, dyspareunia decreased significantly post-operatively in the LAVH group (p < 0.05), but not in the TLH group. A significant reduction in the frequency of orgasms after surgery was detected in both groups (p < 0.05). In conclusion, LAVH has advantages over TLH with reduced operating time. Although it is a technical challenge, TLH can be effectively performed within reasonable time limits in selected cases. The effects on sexual function, following either LAVH or TLH, are found to be similar.     

Spontaneous intracranial hemorrhage caused by pheochromocytoma in a child

We report a 6-year-old boy who presented with left occipital spontaneous lobar hematoma and hypertension. Cerebral angiography failed to demonstrate a vascular malformation. Subsequently, a left adrenal tumor was found that proved to be a pheochromocytoma. This is the first report in the literature of a lobar hematoma in a child caused by a concomitant pheochromocytoma. In children with hypertension and resulting intracerebral hematoma, a pheochromocytoma should be considered in the differential diagnosis.     

An anomaly within the Latino epidemiological paradox: the Latino adolescent male mortality peak

OBJECTIVE: To describe the anomaly of the Latino adolescent male mortality peak in relation to the overall Latino epidemiological paradox and in relation to the need for new conceptual models describing the health of a culturally diverse population. DESIGN: Population-based study using California's 1989 to 1997 summary death files for death-related information and the State of California Department of Finance population estimates for population denominators for corresponding years. PARTICIPANTS: California's general population for 1989 to 1997, including California's 15- to 19-year-old and 20- to 24-year-old populations. In 1997, those 2 age groups numbered 4.3 million. MAIN OUTCOME MEASURES: Mortality rates for Latinos and African Americans compared with non-Hispanic whites expressed as relative risk (RR). RESULTS: Overall, the Latino RR of mortality follows the Latino epidemiological paradox in that it is lower (RR, <1.00) than that of non-Hispanic whites for most age groups and both sexes. The anomaly within this paradox is seen in Latino males aged 15 to 19 years (RR, 1.77; 95% confidence interval, 1.55-2.02) and 20 to 24 years (RR, 1.79; 95% confidence interval, 1.58-2.02). CONCLUSIONS: This period of elevated mortality risk is labeled the Latino adolescent male mortality peak, and it is an anomaly within the overall Latino epidemiological paradox.     

Morphology,GluR1 and GRIP-C localization differ in octopus cells of C57BL6 and B6Cast mice

Air conduction (AC) versus bone conduction (BC) loudness balance testing was conducted at frequencies of 0.25, 0.5, 0.75, 1, 2, and 4 kHz for two groups: 23 normal hearing subjects and eight subjects with a mild to moderate pure sensorineural hearing loss. Narrow-band noise was presented interchangeably between earphones and a bone transducer fitted to the subjects. Loudness matching was carried out at each frequency and at the levels 30-80 dB hearing level (HL) (10 dB steps) in the following manner: the sound pressure from the earphones was fixed and the subject adjusted the output level of the bone transducer for equal loudness by bracketing the standard. The results revealed somewhat different loudness functions for AC and BC sound with a 6-10 dB difference in the AC and BC loudness functions for the normal hearing group over the dynamic range 30-80 dB HL at the frequencies 250-750 Hz. At the higher frequencies, 1-4 kHz, the difference was only 4-5 dB over the same dynamic range. Similar results were obtained for the sensorineural hearing-impaired group. The difference between the AC and the BC loudness functions may originate from changes with level of the AC sound path, e.g. contraction of the stapedius muscle, but also distortion from the bone transducer and tactile stimulation could have contributed to the results seen.