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Biomedical subjects

F F Liu

Publications and source records attributed to F F Liu.

At least 19 recordsLinked to original sources
PubMed1997

Relationship between thermal dose and outcome in thermoradiotherapy treatments for superficial recurrences of breast cancer: data from a phase III trial.

PURPOSE: The objective of this study was to determine whether the thermal dose delivered during hyperthermia treatments and other thermal factors correlate with outcome after combined radiation and hyperthermia of breast carcinoma recurrences. Data were from the combined hyperthermia and radiation treatment arms of four Phase III trials, which when pooled together, demonstrated a positive effect of hyperthermia. METHODS AND MATERIALS: Four Phase III trials addressing the question of whether hyperthermia could improve the local response of superficial recurrent breast cancer to radiation therapy were combined into a single analysis. Thermal dosimetry data were collected from 120 of the 148 breast cancer recurrence patients who received hyperthermia. The data were analyzed for correlations between thermal parameters as well as important clinical parameters and outcome (complete response rate, local disease free survival, time to local failure, and overall survival). RESULTS: Five thermal parameters were tested, all associated with the low regions of the measured temperature distributions. Max(TDmin) and Sum(TDmin) were associated with complete response where TDmin is the minimum thermal dose measured by any of the tumor temperature sensors during a treatment: Max(TDmin) is the maximum of TDmin over a series of treatments. Using a categorical relationship with a cutoff of 10 min for Sum(TDmin), the complete response rate was 77% for Sum(TDmin) > 10 min and 43% for Sum(TDmin) < or = 10 min (p = 0.022, adjusted for study center and significant clinical factors). The overall complete response rate for hyperthermia and radiation was 61% compared to 41% for radiation alone. Either Max(TDmin) or Sum(TDmin) were also associated with local disease free survival, time to local failure and overall survival. CONCLUSIONS: An earlier report of this trial demonstrated a significant benefit when hyperthermia was added to radiation in the treatment of breast cancer recurrences. The analysis of thermal factors demonstrates that parameters representative of the low end of the measured temperature distributions are associated with initial complete response rate, local disease-free survival, time to local failure and overall survival.

Breast Neoplasms↗
PubMed1997

Prenatal diagnosis of cephalothoracopagus janiceps monosymmetros.

We report a case of cephalothoracopagus janiceps monosymmetros that was diagnosed prenatally by ultrasound at 23 weeks' gestation. Obstetric ultrasound demonstrated conjoined female twins with a single fused cranial vault irregular in contour, duplicated cerebra, one face, two eyeballs, a fused thorax, two hearts, two thoracic spines, eight limbs, and polyhydramnios. The pregnancy was terminated and all the features described prenatally were observed at necropsy. The asymmetrical fused faces consisted of a ventral humanoid face with micrognathia, microphthalmia, low-set ears, a normal nose, and an opposite reduced face with partial facial features of a central narrowed fissure and paired synotic ears. The conjoined twins had fused umbilical cords, omphalocoele, and a single oesophagus, stomach, and duodenum, but duplicated pancreases, spleens, and central nervous, cardiopulmonary, hepatic, and genito-urinary systems. The common gastrointestinal tract bifurcated at the level of the jejunum. Our case documents a very uncommon variety of asymmetrical cephalothoracopagus janiceps with duplicated central nervous systems.

Adult↗
PubMed1997

Skeletal deformities of acardius anceps: the gross and imaging features.

A morphology based imaging review is presented of the characteristic skeletal deformities associated with acardius anceps in three acardiac twins. These fetuses demonstrated poorly developed skulls, limb reduction defects, and phocomelia of the upper limbs, as well as narrow thoracic cages with or without the complete development of ribs, clavicles, scapulae, and cervical, thoracic, or lumbar vertebrae. However, their lower limbs and pelvic girdles were almost normal. The authors conclude that skeletal development is likely to be jeopardized in the area adjacent to the heart and in the cephalic portion of the body in fetuses with acardius anceps, and suggest vascular deficiency and hypoperfusion as pathogenetic mechanisms in this type of skeletal deformity.

Abnormalities, Severe Teratoid↗
PubMed1997

Intracellular pH and heat sensitivity in two human cancer cell lines.

BACKGROUND AND PURPOSE: The majority of studies which have demonstrated a linear correlation between intracellular pH (pHi) and thermosensitivity have used rodent cell lines. In order to understand the therapeutic potential of this strategy, it is necessary to determine whether similar observations can be obtained with human cancer cells. MATERIALS AND METHODS: Human breast cancer MCF-7, and nasopharyngeal carcinoma CNE-1 cell lines were heated at 43 degrees C under extracellular pH (pHe) conditions of 7.2 or 6.8, +/- NaHCO3. We studied the function of the Na+/H+ antiport, one of the primary membrane regulators of pHi, pHi level, and clonogenic survival after these treatments. RESULTS: After 2-h exposure to 43 degrees C at pHe 7.2, antiport activity in MCF-7 cells was > 50% relative to that of unheated cells, in contrast to < 20% relative activity for CNE-1 cells. Respective survival levels under these conditions were 0.25 and 0.04. The addition of 5-(N-ethyl-N-isoproply) amiloride (EIPA), a potent inhibitor of Na+/H+ antiport, had no effect on MCF-7 cells, but enhanced cytotoxicity for CNE-1 cells, when heated at pHe 6.8 without NaHCO3. Analysis of the correlation between log surviving fraction and pHi demonstrated that this relationship was much steeper for CNE-1 compared to MCF-7 cells. CONCLUSION: The relationship between pHi levels and thermosensitivity observed in rodent cells can also apply to two human cancer cell lines: MCF-7 and CNE-1, with the latter cells being apparently more amenable to manipulations of pHi regulation compared to the former.

Amiloride↗
PubMed1997

First report of distal obstructive uropathy and prune-belly syndrome in an infant with amniotic band syndrome.

We describe the first report of distal obstructive uropathy and prune-belly syndrome in an infant with amniotic band syndrome. Prenatal ultrasonographic examination in the third trimester revealed intermittent oligohydramnios, bilateral hydronephrosis, and megacystis. Postnatally, the infant was found to have a scalp defect, a skin pedicle, pseudosyndactyly and constriction rings on the hands, marked distention of the abdomen, a fibrous band attached to the proximal urethra causing urethral stricture, a swollen penile shaft, bilateral talipes equinovarus, and syndactyly of the feet. Multiple fibrous amniotic bands could be identified in the placenta. Our case shows that fetal distal obstructive uropathy can be associated with the congenital constriction band syndrome.

Adult↗
PubMed1997

Perinatal features of omphalocele-exstrophy-imperforate anus-spinal defects (OEIS complex) associated with large meningomyeloceles and severe limb defects.

Omphalocele-Exstrophy-Imperforate anus-Spinal defects (OEIS complex), a combination of omphalocele, exstrophy of the bladder, an imperforate anus and spinal defects, arises from a single localized defect in the early development of the mesoderm that will later contribute to infraumbilical mesenchyme, cloacal septum, and caudal vertebrae. In this report, we document the perinatal features of two cases of OEIS complex associated with meningomyeloceles and severe lower limb defects, and discuss the prenatal diagnosis, inheritance, and differential diagnosis of this association of malformations. Although long-term survival can be achieved by successful corrective surgery, the associated structural defects such as large meningomyelocele and severe limb aplasia or hypoplasia, as seen in our patient, can influence the patient's quality of life. We would like to emphasize that an accurate prenatal diagnosis of OEIS complex and associated malformations is important for the detailed counseling of the family as well as appropriate perinatal management by the obstetricians, pediatric surgeons, urologists, neurosurgeons, and neonatologists.

Abnormalities, Multiple↗
PubMed1997

Cebocephaly, alobar holoprosencephaly, spina bifida, and sirenomelia in a stillbirth.

Cebocephaly and sirenomelia are uncommon birth defects. Their association is extremely rare; however, the presence of spina bifida with both conditions is not unexpected. We report on a female still-birth with cebocephaly, alobar holoprosencephaly, cleft palate, lumbar spina bifida, sirenomelia, a single umbilical artery, and a 46,XX karyotype, but without maternal diabetes mellitus. Our case adds to the examples of overlapping cephalic and caudal defects, possibly related to vulnerability of the midline developmental field or axial mesodermal dysplasia spectrum.

Abnormalities, Multiple↗
PubMed1997

Prenatal diagnosis, pathology, and genetic study of fetus in fetu.

We report the prenatal diagnosis, pathology, cytogenetics, and molecular studies of a retroperitoneal fetus in fetu. Prenatal ultrasonography of the host fetus in the third trimester showed an anencephalic, acardiac mass with identifiable extremities and spine within an intra-abdominal cystic mass. Pathological examination revealed a fetiform mass weighing 20 g with four extremities, digits, vertebral bodies, an oral cavity with developing teeth, primitive male external genitalia, a urinary bladder, a cloaca with an external opening, large intestines, a membranous capsule, and an umbilical cord with one artery, one vein, and Wharton's jelly. Histological examination demonstrated nerve bundles in the fibrocollagenous tissue below the cuboidal surface epithelium of the membranous capsule, and absence of lamina elastica interna and vasa vasorum in the single artery of the umbilical cord. Both the host infant and the fetus in fetu had a normal 46,XY karyotype. Molecular analysis using informative genetic markers showed no genetic difference between the host infant and the fetiform mass. We report this case as an unusual example of fetus in fetu in co-existence with an amnion-like membrane containing nerve bundles and with a well-formed umbilical cord. We demonstrate that fetus in fetu can be diagnosed prenatally if the fetiform mass has well-developed limbs and spine. We emphasize the necessity for suspicion of fetus in fetu when a well-defined encapsulated cystic mass with calcified solid components is detected prenatally in a fetus by ultrasonography.

Adult↗
PubMed1997

Progressive fetal axillary cystic lymphangioma with coexistent naevus flammeus.

We report the rare occurrence of a progressive fetal axillary cystic lymphangioma coexistent with an overlying naevus flammeus. The fetus at 22 weeks' gestation was found to have a 37 x 35 mm left axillary multiloculated mass without colour-flow imaging. Amniocentesis showed a normal 46,XX karyotype. Multiple fine-needle aspirations of the mass in the second and third trimesters obtained blood-stained chocolate-coloured fluid containing numerous erythrocytes and lymphocytes but proved ineffective in lessening the progressive growth of the mass. The mother underwent caesarean delivery and a healthy neonate was born with a 141 x 81 mm left axillary cystic lymphangioma and a 50 x 35 mm coexistent naevus flammeus. The neonate was well after simple excision of the lesions. Although cystic lymphangiomas arising in the axilla enlarge progressively during fetal life, our case suggests a good prognosis and except for genetic evaluation, no prenatal intervention is required.

Adult↗
PubMed1997

Cutis marmorata telangiectatica congenita associated with an elevated maternal serum human chorionic gonadotrophin level and transitory isolated fetal ascites.

A 34-year-old woman with an abnormal maternal serum screening result and a Down syndrome risk of 1:60 calculated from a maternal serum alpha-fetoprotein (AFP) value of 1.4 multiples of the median (MoM) and a human chorionic gonadotrophin (hCG) level of 4.32 MoM at 18 weeks' gestation was found to have isolated fetal ascites at 23 weeks' gestation. Spontaneous resolution occurred 10 weeks after the initial presentation. After birth, the neonate had generalized cutis marmorata telangiectatica congenita (CMTC), large vascular plaques on the scalp with superficial ulceration and crusts, a small atrial septal defect, a patent ductus arteriosus, hepatomegaly, micrognathia, seizures, an abnormal electroencephalogram, congenital retinal detachment, glaucoma and widely spaced toes. Our patient illustrates that CMTC in utero may be associated with a markedly elevated maternal serum hCG level as well as transitory isolated fetal ascites. However, such associations can be coincidental and further collaborative studies and cases will be necessary before it can be determined that a disproportionately elevated hCG level and transitory isolated fetal ascites are predictive of CMTC in utero.

Abnormalities, Multiple↗
PubMed1997

Prenatal diagnosis of a deletion of 18q in a fetus associated with multiple-marker screen positive results.

We report here the observations of positive maternal serum screening tests for Down syndrome, cytogenetic and molecular analysis, and dysmorphic fetal features in a pregnancy with 18q-syndrome. A 33-year-old primigravida was referred for genetic counselling because of multiple-marker screen positive results. At 14 weeks' gestation, the woman had a Down syndrome risk of 1:107 calculated from a maternal serum alpha-fetoprotein (MSAFP) level of 1.49 multiples of the median (MOM), a total human chorionic gonadotrophin (hCG) level of 2.42 MOM, and a serum unconjugated oestriol (uE3) level of 0.55 MOM. At 17 weeks' gestation, a repeat test showed a Down syndrome risk of 1:10 calculated from an MSAFP level of 1.09 MOM and a free beta-hCG level of 12.3 MOM. Genetic amniocentesis revealed a de novo deletion of 18q22.2-qter. Intrauterine fetal death occurred at 21 weeks' gestation. At birth, the fetus manifested clinical findings of the 18q-syndrome. The phenotype was correlated with the extent of the deletion. Linkage analysis of the family confirmed the extent and paternal origin of the deletion.

Adult↗
PubMed1996

Radiotherapy with or without hyperthermia in the treatment of superficial localized breast cancer: results from five randomized controlled trials. International Collaborative Hyperthermia Group.

PURPOSE: Claims for the value of hyperthermia as an adjunct to radiotherapy in the treatment of cancer have mostly been based on small Phase I or II trials. To test the benefit of this form of treatment, randomized Phase III trials were needed. METHODS AND MATERIALS: Five randomized trials addressing this question were started between 1988 and 1991. In these trials, patients were eligible if they had advanced primary or recurrent breast cancer, and local radiotherapy was indicated in preference to surgery. In addition, heating of the lesions and treatment with a prescribed (re)irradiation schedule had to be feasible and informed consent was obtained. The primary endpoint of all trials was local complete response. Slow recruitment led to a decision to collaborate and combine the trial results in one analysis, and report them simultaneously in one publication. Interim analyses were carried out and the trials were closed to recruitment when a previously agreed statistically significant difference in complete response rate was observed in the two larger trials. RESULTS: We report on pretreatment characteristics, the treatments received, the local response observed, duration of response, time to local failure, distant progression and survival, and treatment toxicity of the 306 patients randomized. The overall CR rate for RT alone was 41% and for the combined treatment arm was 59%, giving, after stratification by trial, an odds ratio of 2.3. Not all trials demonstrated an advantage for the combined treatment, although the 95% confidence intervals of the different trials all contain the pooled odds ratio. The greatest effect was observed in patients with recurrent lesions in previously irradiated areas, where further irradiation was limited to low doses. CONCLUSION: The combined result of the five trials has demonstrated the efficacy of hyperthermia as an adjunct to radiotherapy for treatment of recurrent breast cancer. The implication of these encouraging results is that hyperthermia appears to have an important role in the clinical management of this disease, and there should be no doubt that further studies of the use of hyperthermia are warranted.

Breast Neoplasms↗
PubMed1996

CVS-exposed limb deficiency defects with or without other birth defects: presentation of six cases born during a period of nine years.

We report on six cases with CVS-exposed limb-"reduction" defects born in our hospital during a period of 9 years (1986-1994). Four cases were associated with other birth defects. One had an oromandibular-limb hypogenesis syndrome with a cleft lip and jejunal atresia, a second had an oromandibular-limb hypogenesis (Hanhart) syndrome, a third had severe flexion deformity at the hips and hyperextension at the knees with meconium peritonitis and intestinal obstruction, and a fourth had Poland anomaly. Detailed clinical descriptions, prenatal diagnosis, photographs, and radiographs are presented. Our presentation adds to the information on severe limb abnormalities after CVS and suggests CVS-exposed limb defects may be associated with other birth defects resulting from vascular insufficiency or intrauterine compression. We suggest that detailed post-CVS sonographic followups are necessary for each CVS-exposed case to identify not only the possible fetal limb reduction, but also vascular disruption-type malformations and compressive deformities.

Abnormalities, Multiple↗
PubMed1996

The stress-activated protein kinase pathway mediates cell death following injury induced by cis-platinum, UV irradiation or heat.

BACKGROUND: Stimuli that stress cells, including inflammatory cytokines, ultra-violet irradiation, DNA-damaging chemotherapeutic drugs and heat shock, stimulate a recently identified cytoplasmic signaling system that is structurally related to the mitogen-activated protein kinase pathway. This pathway consists of a cascade of protein kinases including stress-activated protein kinase (SAPK), also termed Jun N-terminal kinase (JNK), and two kinases that activate it, MEKK and SEK/MKK4. Despite rapid progress in delineating the components of this pathway, the cellular consequence of its activation remains to be defined. RESULTS: We have screened cells for defects in SAPK signaling and identified a cell line, previously characterized for its thermotolerance properties, as being more refractive to SAPK activation induced by heat stress than its thermosensitive parental line. Stable expression of dominant inhibiting SEK mutants in thermosensitive parental cells specifically and effectively blocked SAPK activation after heat shock. These lines also became markedly resistant to the cytocidal effects of thermal stress, confirming the phenotype of the thermotolerant line. These cell lines defective in SAPK activation were also resistant to the lethal effects of the DNA-damaging drug cis-platinum. CONCLUSIONS: Experimentally induced stable blockade of SAPK activation in cells with normal thermosensitivity is sufficient to confer resistance to cell death induced by diverse stimuli including heat and the chemotherapeutic agent cis-platinum. These results suggest that activation of the SAPK pathway by diverse cell stressors plays a critical part in mediating the toxicity of these treatments and inducing cell death. SAPK activation in this context could broadly influence cellular response to stress, modulate apoptosis during development or determine the clinical response of tumor cells to cytotoxic therapies.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed1996

The effect of heat on Na+/H+ antiport function and survival in mammalian cells.

PURPOSE: Because intracellular pH (pHi) is a determinate of thermosensitivity, it is important to understand the relationship between heat cytotoxicity and the mechanisms responsible for pHi regulation, such as the Na+/H+ antiport. The objective of this study is to elucidate the relationship between heat damage and Na+/H+ antiport activity. METHODS AND MATERIALS: Various cell lines, EMT6, RIF-1, and its thermoresistant variant TR-4, and CCL39, and its variant that lacks the Na+/H+ antiport (PS120), were all heated using a water bath. Parallel assessments of antiport function and pHi were made using the fluorescent dye 2,7-biscarboxyethyl-5(6)-carboxyfluorescein (BCECF). RESULTS: Exposure of EMT6 cells to 43-46 degrees C for 30-60 min caused progressive decline in antiport activity, in parallel with cytotoxicity. When the same degree of cytotoxicity was induced by ionizing radiation, no alteration in Na+/H+ antiport function was observed. Despite a 10-fold lower survival in RIF-1 compared to TR-4 cells after heating, there was no difference in the thermosensitivity of their antiports. Antiport activity in the TR-4 cells, however, was higher than that of RIF-1 cells both before and during heating. Intracellular pH for TR-4 cells decreased minimally during heating, in contrast to a decline of 1 pH unit in RIF-1 cells despite similar relative levels of antiport activity, suggesting that in this pair of cell lines, antiport activity does not play a major pHi regulatory role. PS120 and CCL39 cells and similar survival levels when heated at pHe 7.2 in the presence of NaHCO3, which allows function of the other major regulator of pHi, the Na+ -dependent HCO3-/Cl- exchanger. This occurred despite a drop in pHi in the PS120 cells during heating. A reduced survival was observed, however, in PS120 cells after 43 degrees C for 30-60 min at either pHe 6.5 or pHe 7.2 in the absence of NaHCO3. Intracellular pH was consistently greater for PS120 than CCL39 cells. CONCLUSION: We demonstrated that damage to the Na+/H+ antiport likely reflects early heat-induced change in membrane function, but is not a primary target for heat cytotoxicity. Although there is an association between survival, antiport function, and pHi level under most treatment conditions, the precise role of the Na+/H+ antiport in mediating thermal cytotoxicity remains uncertain.

Animals↗
PubMed1996

Prenatal diagnosis of partial monosomy 3p and partial trisomy 2p in a fetus associated with shortening of the long bones and a single umbilical artery.

The prenatal and postnatal findings of a fetus with partial deletion of 3p25 -> pter and duplication of 2p25.3 -> pter are described. The proband postnatally displayed mental and growth retardation, psychomotor delay, microcephaly, ptosis, micrognathia, a narrow palate, and cryptorchidism. All of these anomalies were consistent with those described in 3p- and partial trisomy 2p syndromes, and also frequently seen in patients with other chromosomal disorders. However, the prenatal sonograms revealed unusual shortening of the long bones, a single umbilical artery, and normal development of the skull. Our case suggests that skeletal growth retardation of the long bones may occur earlier than that of the skull in fetuses associated with chromosomal aberrations such as del(3p)/dup(2p). Shortening of the long bones and a single umbilical artery together with other abnormalities detected by prenatal ultrasound thus warrant a fetal cytogenetic study.

Abnormalities, Multiple↗
PubMed1996

Ultrasound-guided fluid aspiration and prenatal diagnosis of duplicated hydrometrocolpos with uterus didelphys and septate vagina.

We report on a case of duplicated hydrometrocolpos with uterus didelphys, a septate vagina, lower vaginal atresia, a persistent urogenital sinus, left ear agenesis, a single umbilical artery, and an imperforate anus, but without the associated features of McKusick-Kaufman syndrome such as polydactyly and congenital heart defects. Ultrasound-guided fluid aspiration of the fetal intrapelvic cystic mass helped to decompress the distended genital organs, decrease the severity of the urinary tract obstruction, delineate the ultrasonographic image of duplicated hydrometrocolpos to differentiate it from other intrapelvic cystic masses, and obtain fluid for cytological analysis.

Abnormalities, Multiple↗