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81.
PURPOSE: p27(Kip1) is a member of the Cip1/Kip1 family of cyclin-dependent kinase inhibitors and is a potential tumor suppressor gene. Low levels of p27 are associated with poor prognosis in a variety of gynecological tumors, including breast, ovarian, and cervical carcinomas. The role of p27 in endometrial cancer remains controversial. EXPERIMENTAL DESIGN: In the present study, p27 protein expression was investigated by immunohistochemistry in a series of 217 endometrial adenocarcinomas and, where present, in synchronous normal endometrium, simple and complex hyperplasia (with or without atypia), and cystic atrophy. The relationship between p27 expression and clinical outcome was also evaluated. RESULTS: Immunohistochemical analysis revealed a significant loss of p27 expression from normal (33%) through hyperplastic endometrium (50%) to endometrial adenocarcinomas (71%; P 相似文献   
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Postoperative speech function may be influenced by a number of treatment variables. The objective of this study was to examine the relationships among various treatment factors to determine the impact of these measures on speech function. Speech function was tested prospectively in 142 patients with surgically treated oral and oropharyngeal cancer 3 months after treatment. Each patient's speech was recorded during a 6- to 7-minute conversation and while performing a standard articulation test, producing speech outcome measures of percent correct consonant phonemes and percent conversational understandability. Correlational analyses were used to determine the relationships among the speech outcome measures and 14 treatment parameters. Speech function was mildly to moderately negatively correlated with most surgical resection variables, indicating that larger amounts of tissue resected were associated with worse speech function. Overall measures of conversational understandability and percent correct consonant phonemes were related to extent of oral tongue resection, floor of mouth resection, soft palate resection, and total volume of tissue resected. These relationships varied depending on the method of surgical closure. Method of surgical reconstruction had a profound impact on postoperative speech function 3 months after treatment and was an important factor in determining how oral tongue resection influenced articulation and intelligibility. The combination of closure type, percent oral tongue resected, and percent soft palate resected had the strongest relationship with overall speech function for patients with surgically treated oral and oropharyngeal cancer 3 months after treatment.  相似文献   
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OBJECTIVE: To determine the effects of monophasic oral contraceptives on the nasal respiratory epithelium in premenopausal women. DESIGN: Prospective open clinical trial. SETTING: Outpatient Family Planning Centre. PATIENT(S): Eighty-eight premenopausal women, with ovulatory cycle, who were planning to take oral contraceptives. INTERVENTION(S): Baseline endovaginal ultrasound examination and blood test to measure serum progesterone to confirm ovulatory cycle. Thirty-eight women on pill containing 30 microg ethinylestradiol (EE) plus 75 microg gestodene, and 35 women on pill containing 15 microg ethinylestradiol plus 60 microg gestodene. MAIN OUTCOMES/MEASURE(S): Cytological changes on the nasal respiratory epithelium evaluated with the maturation index performed during the follicular, periovular, and luteal phases of the menstrual cycle, and on the sixth cycle of pill intake. RESULT(S): Hematoxylin-eosin staining for the maturation index showed similar trophic cytological aspects between the nasal and vaginal epithelium during the menstrual cycle and pill usage. Both the nasal and vaginal cytological samples showed higher maturation indexes during both the follicular and the periovular phases than during the luteal phase. Women on pill containing 15 microg EE showed lower trophic aspects in the nasal cytological samples compared with those on pill with 30 microg EE. CONCLUSION(S): Along with the vaginal cells, the nasal respiratory epithelium is an ovarian steroid target. The maturation index of the nasal respiratory epithelium seems to depend on the variation of the ovarian steroids during the menstrual cycle and on the iatrogenic effects of oral contraceptives.  相似文献   
87.
The activation of poly(ADP-ribose) polymerase (PARP) is well considered to play an important role in various patho-physiological conditions like inflammation and shock. A vast amount of circumstantial evidence implicates oxygen-derived free radicals (especially, superoxide and hydroxyl radical) and high-energy oxidants (such as peroxynitrite) as mediators of inflammation and shock. ROS (e.g., superoxide, peroxynitrite, hydroxyl radical and hydrogen peroxide) are all potential reactants capable of initiating DNA single strand breakage, with subsequent activation of the nuclear enzyme poly(ADP-ribose) synthetase (PARS), leading to eventual severe energy depletion of the cells, and necrotic-type cell death. During the last years, numerous experimental studies have clearly demonstrated the beneficial effects of PARP inhibition in cell cultures through rodent models and more recently in pre-clinical large animal models of acute and chronic inflammation. The aim of this review is to describe recent experimental evidence implicating PARP as a pathophysiological modulator of acute and chronic inflammation.  相似文献   
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Interleukin-6 (IL-6) protects multiple myeloma cells against apoptosis induced by glucocorticoids. Here, we investigated whether inhibition of the IL-6 signaling pathway by the IL-6 receptor superantagonist Sant7 enhances the in vivo antitumor effects of dexamethasone on the IL-6-dependent multiple myeloma cell line INA-6. For this purpose, we used a novel murine model of human multiple myeloma in which IL-6-dependent INA-6 multiple myeloma cells were directly injected into human bone marrow implants in severe combined immunodeficient (SCID) mice (SCID-hu). The effect of in vivo drug treatments on multiple myeloma cell growth was monitored by serial determinations of serum levels of soluble IL-6 receptor (shuIL-6R), which is released by INA-6 cells and served as a marker of tumor growth. In SCID-hu mice engrafted with INA-6 cells, treatment with either Sant7 or dexamethasone alone did not induce significant reduction in serum shuIL-6R levels. In contrast, the combination of Sant7 with dexamethasone resulted in a synergistic reduction in serum shuIL-6R levels after 6 consecutive days of treatment. Gene expression profiling of INA-6 cells showed down-regulation of proliferation/maintenance and cell cycle control genes, as well as up-regulation of apoptotic genes in multiple myeloma cells triggered by Sant7 and dexamethasone combination. In vitro colony assays showed inhibition of myeloid and erythroid colonies from normal human CD34(+) progenitors in response to dexamethasone, whereas Sant7 neither inhibited colony growth nor potentiated the inhibitory effect of dexamethasone. Taken together, these results indicate that inhibition of IL-6 signaling by Sant7 significantly potentiates the therapeutic action of dexamethasone against multiple myeloma cells, providing the preclinical rationale for clinical trials of Sant7 in combination with dexamethasone to improve patient outcome in multiple myeloma.  相似文献   
90.

Study Objective

To describe the potential role of intraoperative ultrasound (IOUS) in the detection and localization of recurrent disease in gynecologic cancer patients during minimally invasive surgery (MIS).

Design

A prospective cohort study (Canadian Task Force classification II-1).

Setting

A university hospital.

Patients

Fifty-one gynecologic cancer patients with isolated recurrent disease.

Interventions

IOUS during secondary cytoreductive surgery (SCS) by MIS.

Measurements and Main Results

From November 2015 to February 2017 51 gynecologic cancer patients with isolated recurrent disease and candidates for SCS were treated by MIS. Recurrent tumor was preoperatively assessed at clinical examination, transvaginal and transabdominal sonography, and radiologic evaluation in all women. Twelve of 51 women (23.5%) needed IOUS. Type of disease was ovarian in 5 women (42%), endometrial in 4 (33%), cervical in 1 (8%), vaginal cancer in 1 (8%), and uterine sarcoma in 1 (8%). Recurrence was localized deep in the pelvis in 7 cases (58%), lymph nodes in 3 (25%), and extraperitoneal in 2 cases (17%). Recurrence was dimmed in the surgical field, due to either presence of adherences, deep anatomic position, small size, and/or lack of tactile feeling. IOUS was able to identify the lesions in all women, allowing MIS (83% laparoscopy and 17% robotic) complete cytoreduction, with no conversion to laparotomy. Median operative time was 150 minutes (range, 77–280). No intraoperative/postoperative complications occurred. Histologic examination confirmed the presence of recurrence in 11 of 12 cases (92%), whereas the remaining case showed inflammatory tissue. With a median follow-up time of 15 months (range, 6–19), all patients except 2 were still alive.

Conclusions

About 1 of 4 patients (25%) with single gynecologic cancer recurrence needs IOUS to benefit from MIS for complete secondary cytoreduction.  相似文献   
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