Biomedical subjects

A K Sood

Publications and source records attributed to A K Sood.

At least 19 recordsLinked to original sources

PubMed2001

Application of the National Cancer Institute international criteria for determination of microsatellite instability in ovarian cancer.

Recently, the National Cancer Institute (NCI) established criteria for determination of microsatellite instability (MSI) in colorectal tumors. Although the best panel of markers for ovarian tumors is not known, we evaluated epithelial ovarian cancers for MSI based on the NCI recommendations. One hundred and nine ovarian tumors were analyzed for MSI by gel analysis of paired germ-line and tumor DNA. PCR amplification was performed using the panel of five microsatellite markers recommended by the NCI (BAT25, BAT26, D5S346, D2S123, and D17S250) and nine additional markers picked based on their genomic location (NME1, D10S197, D11S904, D13S175, DXS981, DXS6800, DXS6807, AR, and D3S1611). Tumors were characterized on the basis of: high-frequency MSI (MSI-H) if two or more of the five NCI markers showed instability or there was instability at 30% or more of all markers tested; or low-frequency MSI (MSI-L) if only one of the five NCI markers showed instability or <30% of all of the markers. All of the other tumors were considered microsatellite stable. On the basis of the NCI markers, 12 (11%) tumors demonstrated MSI-H, and 8 (7%) additional tumors had MSI-L. When all of the 14 markers were considered together, 13 (12%) tumors demonstrated MSI-H (based on 30% or more unstable loci), and 26 (24%) tumors had MSI-L. A single tumor identified to have MSI-H based upon all of the markers tested would have been classified as MSI-L based upon the NCI markers alone. Inclusion of an additional dinucleotide marker (NME1) to the NCI panel allowed detection of all of the tumors with MSI-H using only six markers. MSI-H occurs in approximately 12% of invasive ovarian tumors. For optimal detection of microsatellite instability in ovarian cancer, an additional marker (NME1) may be required, along with the five recommended by the NCI.

DNA, Neoplasm↗

PubMed2001

Observation of a topological relaxation mode in microemulsions.

We report the observation of two diffusive relaxation modes in a very swollen microemulsion, measured by quasielastic light scattering experiments. In addition to a short-time diffusion process, we observe a long-time diffusive relaxation mode with unusual scaling behavior: the diffusion constant D is an exponential function of the characteristic length scale xi, D~exp(-xi). This observation provides experimental evidence for thermally activated topological relaxation of random fluid phases, as predicted by Milner et al. [J. Phys. (Paris) 51, 2629 (1990)]. We describe the activation energy of such a process by some simple microscopic model for the surfactant layer and give an estimation of the membrane elastic and Gaussian moduli kappa and kappa;, and its spontaneous curvature.

Journal Article↗

PubMed2001

Recurrent carcinoma in situ of a neovagina.

BACKGROUND: Development of carcinoma in situ in a neovagina is rare. CASE: A case of carcinoma in situ of a neovagina complicated by recurrence after ablative therapy is discussed. Recurrence occurred within 4 months of initial therapy, and a total vaginectomy was performed after the patient declined other therapeutic options. CONCLUSION: Recurrent carcinoma in situ of a neovagina can be successfully treated by surgical excision.

Carcinoma in Situ↗

PubMed2001

Paclitaxel and platinum chemotherapy for ovarian carcinoma during pregnancy.

BACKGROUND: Ovarian cancer diagnosed during pregnancy is uncommon. Paclitaxel-based chemotherapy during pregnancy has not been reported previously. CASE: A woman with ascites and an adnexal mass diagnosed during pregnancy at 27 weeks gestational age underwent a laparotomy with cytoreductive surgery and was diagnosed with stage IIIC papillary serous ovarian adenocarcinoma. She was treated with three cycles of paclitaxel and cisplatin during pregnancy. At 37 weeks, she underwent a cesarean section, abdominal hysterectomy, and cytoreduction. Three additional cycles of chemotherapy were given. She developed a recurrence within 6 weeks of completing chemotherapy. She received several cycles of chemotherapy, but died of recurrent cancer 29 months after diagnosis. The infant has normal growth and development at 30 months of age. CONCLUSION: This is the first reported case of paclitaxel use during pregnancy.

Adult↗

PubMed2001

Papillary serous carcinoma of the uterus: increased risk of subsequent or concurrent development of breast carcinoma.

OBJECTIVE: Some women with endometrial cancer may be at increased risk for developing breast cancer. The histologic type of endometrial cancer associated with synchronous or subsequent breast cancer has not been clearly established. Our purpose was to determine if a certain histologic type of endometrial cancer was associated with an increased risk of synchronous or subsequent breast cancer. METHODS: The University of Iowa Hospitals and Clinics tumor registry was queried to ascertain all patients with the diagnosis of uterine cancer from January 1, 1983, to December 31, 1994. Statistics were performed utilizing SPSS for Windows version 9.0 (SPSS Inc., Chicago, IL), including Student's t tests and chi(2) tests. RESULTS: Five hundred ninety-two patients had endometrial adenocarcinoma during the study period. Five hundred thirty-six women had endometrioid adenocarcinoma, 23 women had papillary serous carcinoma (UPSC), 21 women had adenosquamous carcinoma, 10 women had clear-cell carcinoma, and 1 woman each had mucinous or squamous carcinoma. Twelve patients had previously been diagnosed with breast carcinomas. Twenty-five patients were diagnosed with breast cancer either concurrently or subsequent to their diagnosis of endometrial cancer. Synchronous or subsequent breast cancers developed in 3.2% of patients with endometrioid carcinoma and in 25% of patients with UPSC (P < 0.001). CONCLUSION: Patients with UPSC have an increased risk of development of breast cancer as compared to patients with endometrioid adenocarcinoma of the uterus.

Aged↗

PubMed2001

Molecular determinants of ovarian cancer plasticity.

During development, the formation and remodeling of primary vascular networks occurs by vasculogenesis and angiogenesis. Recently, the term "vasculogenic mimicry" has been used by our laboratory and collaborators to reflect the embryonic-like ability of aggressive, but not nonaggressive, melanoma tumor cells to form a pattern of matrix-rich networks (containing channels) surrounding spheroids of tumor cells in three-dimensional culture, concomitant with their expression of vascular cell markers. Ovarian cancer is usually diagnosed as advanced stage disease in most patients when widespread metastases have already been established within the peritoneal cavity. In this study, we explored whether invasive ovarian carcinoma cells could engage in molecular vasculogenic mimicry reflected by their plasticity, compared with their normal cell counterparts. The data revealed that the invasive ovarian cancer cells, but not normal ovarian surface epithelial cells, formed patterned networks containing solid and hollow matrix channels when grown in three-dimensional cultures containing Matrigel or type I collagen, in the absence of endothelial cells or fibroblasts. Immunohistochemical analysis showed that matrix metalloproteinases (MMP)-1, -2, and -9, and MT1-MMP were discretely localized to these networks, and the formation of the networks was inhibited by treatment with MMP inhibitors. Furthermore, the RNase protection assay revealed the expression of multiple vascular cell-associated markers by the invasive ovarian cancer cells. In patient tumor sections from high-stage, high-grade ovarian cancers, 7 to 10% of channels containing red blood cells were lined by tumor cells. By comparison, all vascular areas in benign tumors and low-stage cancers were endothelial lined. These results may offer new insights and molecular markers for consideration in ovarian cancer diagnosis and treatment strategies based on molecular vascular mimicry by aggressive tumor cells.

Female↗

PubMed2001

p53 Mutations and microsatellite instability in ovarian cancer: Yin and yang.

OBJECTIVE: We tested the hypothesis that p53 frameshift mutations in ovarian cancer occur as a result of genomic instability rather than as a proximal cause of this process. STUDY DESIGN: Sequencing of the p53 tumor suppressor gene has been carried out on 305 ovarian, fallopian tube, and peritoneal cancers. Two groups of p53 null mutations were identified: (1) those caused by frameshift insertion or deletion mutations (n = 31) and (2) those caused by nonsense mutations (n = 28). As a control group 59 tumors with p53 missense mutations were selected by matching with the p53 null tumors on the basis of patient age at diagnosis, stage and grade of cancer, cancer site, and year of diagnosis. Microsatellite instability was determined from paired normal and tumor tissue deoxyribonucleic acid by means of the following different markers: D2S123, D5S346, D17S250, BAT25, and BAT26. Amplimers from polymerase chain reactions were evaluated on 7% polyacrylamide gels. RESULTS: The p53 null tumors were more likely to be of higher stage and grade. Fallopian tube cancers were more common (P =.02) in the p53 frameshift group. The overall incidence of microsatellite instability was 39%, 36%, and 25% for tumors with p53 frameshift nonsense and missense mutations (P =.30). Microsatellite instability was seen almost exclusively with ovarian cancer (P =.04). CONCLUSIONS: Microsatellite instability is a relatively common event in ovarian cancer and is dependent on marker selection. The p53 frameshift mutations do not appear to occur as a consequence of genomic instability.

Adult↗

PubMed2001

Hormone replacement therapy and cancer risk.

The advantages and disadvantages of hormone replacement therapy (HRT) have been debated nearly as long as the treatment has been in use, especially the relationship between HRT and risk of cancer development. It is hoped that recently published studies will shed more light on this complex issue. Several large population studies suggest that there may be a small but increased risk of developing breast cancer in HRT users, especially in estrogen and progesterone users. This risk appears most pronounced after 5 years of HRT use. Endometrial cancer, which has long been associated with unopposed estrogen use, can be successfully prevented with the addition of progestins to the HRT regimen, provided it is given for at least 10 days each month. Estrogen replacement therapy has also been shown to significantly reduce the risk for colon cancer but not rectal cancers. Finally, a large prospective study has linked HRT with an increase in ovarian cancer mortality.

Breast Neoplasms↗

PubMed2001

The p53 mutational spectrum associated with BRCA1 mutant ovarian cancer.

PURPOSE: Cancer-specific p53 mutational spectra have been identified. Data from murine models and human BRCA1-related hereditary breast cancers suggest that both unique and specific BRCA1-associated p53 mutations may be found in BRCA1-related ovarian cancers. EXPERIMENTAL DESIGN: The p53 mutational spectrum from ovarian cancers containing either somatic or germ-line BRCA1 mutations was compared with that of sporadic ovarian cancers defined as those diagnosed with a negative family history for breast/ovarian cancer in a three-generation pedigree. Tumor DNA was screened over exons 2-11 of the p53 gene by the PCR and single-strand confirmation polymorphism analysis of the amplimers. Cycle-based DNA sequencing from separate reactions was used to confirm p53 mutations. RESULTS: p53 gene mutations were detected in 42 of 86 sporadic ovarian cancers, compared with 13 of 15 cancers with somatic BRCA1 mutations (P = 0.007) and 16 of 20 cancers with germ-line BRCA1 mutations (P = 0.01). p53 null mutations were found in 31.4% of BRCA1 mutant cancers, compared with only 9.3% of the sporadic cancers (P = 0.002). The p53 mutational spectrum of germ-line BRCA1-related cancers was shifted toward transversions, frameshifts, and non-CpG transitions relative to the spectrum of sporadic ovarian cancers. Thirty-three unique ovarian cancer p53 mutations were sequenced. However, the specific p53 mutations in the BRCA1 mutant cancers were no more unique to this cohort than the p53 mutations of the sporadic cancers. CONCLUSIONS: Ovarian cancers containing somatic or germ-line BRCA1 mutations are uniformly accompanied by p53 dysfunction. This finding offers additional support to observations regarding the importance of p53/BRCA1 interactions in ovarian carcinogenesis.

BRCA1 Protein↗

PubMed2001

Prostate epithelium-derived Ets transcription factor mRNA is overexpressed in human breast tumors and is a candidate breast tumor marker and a breast tumor antigen.

PURPOSE: There is a need to identify novel breast tumor-associated molecules with a potential as diagnostic/prognostic markers of breast cancer as well as targets of vaccine and drug discovery against this cancer. EXPERIMENTAL DESIGN: We used a combination of digital differential display and reverse transcription-PCR (RT-PCR) methods to identify breast tumor-associated cDNAs. RESULTS: It was found that prostate epithelium-derived Ets transcription factor (PDEF) and five other cDNAs occur at high frequency in the cDNA libraries from normal human breast tissue and human breast tumors. In contrast, these cDNAs are either undetectable or present at low frequencies in the cDNA libraries from other normal human tissues. RT-PCR expression analysis of PDEF showed it to be overexpressed in 14 of 20 primary human breast tumors and in one metastases tested. Also, consistent with the digital differential display data, RT-PCR analysis of PDEF expression showed highly restricted expression in normal human tissues. Furthermore, we show that PDEF transcript levels are 192-fold higher in the peripheral blood of a breast cancer patient in comparison with two normal individuals and another breast cancer patient. In contrast to PDEF, RT-PCR analysis of the expression of the other three cDNAs, including MYL5, Hs.44017, and Hs.215937, showed that these cDNAs are expressed in several normal human tissues. CONCLUSIONS: These results suggest that PDEF is a breast tumor-associated cDNA and should be further evaluated for its potential as a breast tumor marker and a breast tumor antigen.

Antigens, Neoplasm↗

PubMed2000

The prognostic significance of p53 tumor suppressor gene alterations in ovarian carcinoma.

BACKGROUND: The prognostic significance and nature of p53 dysfunction in ovarian carcinoma is unclear. The relation between p53 overexpression, p53 mutations, and their effects on overall survival in primary ovarian carcinoma is explored. METHODS: Tumor specimens from 171 consecutive epithelial ovarian carcinomas were examined for overexpression of p53 protein with DO7 antibody. P53 mutations were determined by direct sequencing. The influences of conventional histopathologic prognostic factors and various p53 molecular alterations on overall survival were assessed. RESULTS: Overall, 48.5% and 57.3% of the samples showed p53 overexpression and p53 mutation, respectively. Although neither p53 overexpression nor the mere presence of a p53 mutation impacted overall survival, the combination did prognosticate survival both in univariate and multivariate models. The authors' results suggest 4 mechanisms that may affect p53 dysfunction in nearly 100% of advanced stage ovarian carcinomas. These include null mutation, nonresponsive p53 (wild-type [wt] p53 sequence, DO7 negative), sequestration (wt p53 sequence, DO7 positive), and missense mutation. Median survival for these groups that constitute sequentially 21.3%, 20.5%, 12.3%, and 45.9% of the 122 Stage III or IV (International Federation of Gynecology and Obstetrics) cancers was 1.49, 1.31, 3.09, and 3.6 years, respectively. The nonresponsive p53 and null sequence tumors grouped together as functionally null convey the worst prognosis relative to missense mutations in a univariate model (P = 0.006). Functionally null p53 (P = 0.002), stage (P = 0.008), and optimal cytoreduction (P = 0.008) were independent prognostic factors by multivariate analysis. CONCLUSIONS: Sequestration of wt p53 is unique to advanced stage ovarian carcinoma. Functionally null p53 represents an independent molecular predictor of compromised survival.

Adult↗

PubMed2000

Preservation of the saphenous vein during inguinal lymphadenectomy decreases morbidity in patients with carcinoma of the vulva.

BACKGROUND: Traditional inguinal lymphadenectomy includes the removal of a portion of the saphenous vein. The authors hypothesized that preserving the saphenous vein would decrease morbidity without affecting treatment outcome. METHODS: A retrospective review of 83 patients with carcinoma of the vulva who underwent inguinal lymphadenectomy between 1990-1998 was performed. Postoperative short term and long term complications were evaluated. RESULTS: A total of 139 inguinal dissections were performed in 83 patients. The saphenous vein was preserved in 62 patients and ligated in 77 patients. The clinical characteristics of the patients, the operating time, and the estimated blood loss were not significantly different between the two groups. The incidence rate of short term complications including fever, seroma, phlebitis, lymphocyst, and deep venous thrombosis also was similar. Cellulitis occurred in 39% of the patients who underwent vein ligation compared with 18% of the patients who underwent a vein-sparing procedure (P = 0.006). Short term (< 6 months) lower extremity lymphedema occurred in 70% of the vein-ligated group compared with 32% of the vein-spared group (P < 0. 001). Chronic edema (>/= 2 years) was present in only 3% of the patients who underwent saphenous vein preservation compared with 32% of those who underwent vein ligation (P = 0.003). Chronic lymphedema in the vein-spared group was observed in only one patient who received postoperative radiation. Overall, individuals with preservation of the saphenous vein were less likely to develop complications (56% vs. 23%; P < 0.001). There was no difference in the rate of incidence of recurrent disease between the two groups. CONCLUSIONS: Preservation of the saphenous vein during inguinal lymphadenectomy reduces both the short term and long term postoperative complications without affecting treatment outcome. The saphenous vein should be preserved routinely in patients undergoing inguinal lymphadenectomy.

Aged↗

PubMed2000

Quality of life and mood in women receiving extensive chemotherapy for gynecologic cancer.

BACKGROUND: Quality of life (QOL) and mood were investigated among women who had received intensive chemotherapy for at least 1 year for advanced gynecologic cancers. Relationships of coping styles to QOL and mood in these patients also were examined. METHODS: Twenty-four patients who had been receiving chemotherapy continuously or intermittently for at least 1 year were recruited into the study. To control for the diagnosis of cancer and for prior hysterectomy, 24 age-matched early stage gynecologic cancer patients not receiving chemotherapy and assessed 1 year following diagnosis were examined as a comparison group. All subjects completed psychosocial assessments at a clinic visit. Medical information was retrospectively abstracted from patient charts. RESULTS: Decrements in physical, emotional, and functional well-being were reported by extensively treated patients, whereas social well-being and satisfaction with the relationship between doctor and patient were close to the norms of the comparison group. Extensively treated patients reported more fatigue and less vigor, but their depression and anxiety did not differ from early stage patients. Almost all extensively treated patients reported that their treatment had been worthwhile. Patients using avoidant coping reported poorer physical and emotional well-being, along with greater anxiety, depression, fatigue, and total mood disturbance. Those using active coping reported better social well-being, better relationships with their doctors, and less overall distress. CONCLUSIONS: This study indicates that gynecologic oncology patients extensively treated with chemotherapy experienced substantial decrements to quality of life, and yet treatment still was considered worthwhile by a majority of patients. Avoidant coping may be a particular risk factor for poor QOL and greater distress.

Adaptation, Psychological↗

PubMed2000

Observation of chaotic dynamics in dilute sheared aqueous solutions of CTAT.

The nonlinear flow behavior of a viscoelastic gel formed due to entangled, cylindrical micelles in aqueous solutions of the surfactant cetyl trimethylammonium tosilate (CTAT) has been studied. On subjecting the system to a step shear rate lying above a certain value, the shear and normal stresses show interesting time dependent behavior. The analysis of the measured time series shows the existence of a finite correlation dimension and a positive Lyapunov exponent, unambiguously implying that the dynamics can be described by that of a dynamical system with a strange attractor whose dimension increases with the increase in shear rate.

Journal Article↗

PubMed2000

Pixel analysis of MR perfusion imaging in predicting radiation therapy outcome in cervical cancer.

The purpose of this study was to assess heterogeneity of tumor microcirculation determined by dynamic contrast-enhanced magnetic resonance (MR) imaging and its prognostic value for tumor radiosensitivity and long-term tumor control using pixel-by-pixel analysis of the dynamic contrast enhancement. Sixteen patients with advanced cervical cancer were examined with dynamic contrast-enhanced MR imaging at the time of radiation therapy. Pixel-by-pixel statistical analysis of the ratio of post- to precontrast relative signal intensity (RSI) values in the tumor region was performed to generate pixel RSI distributions of dynamic enhancement patterns. Histogram parameters were correlated with subsequent tumor control based on long-term cancer follow-up (median follow-up 4.6 years; range 3.8-5.2 years). The RSI distribution histograms showed a wide spectrum of heterogeneity in the dynamic enhancement pattern within the tumor. The quantity of low-enhancement regions (10th percentile RSI < 2.5) significantly predicted subsequent tumor recurrence (88% vs. 0%, P = 0.0004). Discriminant analysis based on both 10th percentile RSI and pixel number (reflective of tumor size) further improved the prediction rate (100% correct prediction of subsequent tumor control vs. recurrence). These preliminary results suggest that quantification of the extent of poor vascularity regions within the tumor may be useful in predicting long-term tumor control and treatment outcome in cervical cancer. J. Magn. Reson. Imaging 2000;12:1027-1033.

Aged↗

PubMed2000

Hematogenous skin metastases from cervical cancer at primary presentation.

OBJECTIVE: Cutaneous metastasis from carcinoma of the uterine cervix is an uncommon occurrence. The majority of cases are diagnosed as recurrent carcinoma. This is believed to be the first report of hematogenous skin metastases present at the diagnosis of cervical carcinoma. METHODS: A case of a patient with cutaneous manifestations at the time of cervical carcinoma diagnosis is presented. RESULTS: Two lesions on the patient's hand occurred at points of recent skin puncture. These were biopsy-proven metastases from her primary cervical carcinoma. CONCLUSION: Skin metastases from cervical carcinoma are rare and represent a poor prognostic sign.

Fatal Outcome↗

PubMed2000

Childhood trichobezoar.

Two cases of trichobezoar with unusual presentation in rural female children are described. The first one in a healthy asymptomatic child with no abnormal psychological behaviour and other one in an emotionally disturbed child with history of trichotillomania. Both were treated surgically with no recurrence. A physical sign of indentibility is discussed and literature is also reviewed.

Bezoars↗

PubMed2000

Cervical cancer diagnosed shortly after pregnancy: prognostic variables and delivery routes.

OBJECTIVE: To compare the prognoses of women diagnosed with cervical cancer during pregnancy with the prognoses of those diagnosed within 6 months after delivery and to assess the effect of vaginal delivery on recurrence risk and prognosis. METHODS: A matched case-control study of women with cervical cancer diagnosed during pregnancy or within 6 months of delivery was performed. Fifty-six women had cervical cancer diagnosed during pregnancy and 27 within 6 months after delivery. Controls (cervical cancer diagnosed at least 5 years since last delivery) were matched one-to-one with cases based on age, histology, stage, treatment, and time of treatment. RESULTS: Among postpartum women, four had stage IA disease, 15 had stage IB1 or IB2, and eight had stage IIA or higher disease. Eleven had radical hysterectomies and 14 had radiation therapy. Two with stage IA1 disease were treated with vaginal hysterectomies. One of seven patients who had cesareans developed a local and distant recurrence. In contrast, ten of 17 (59%) who delivered vaginally developed recurrences (P =.04). In multivariate analysis, vaginal delivery was the most significant predictor of recurrence (odds ratio [OR] 6.91; 95% confidence interval [CI] 1.45, 32.8), followed by high stage (OR 4.66; 95% CI 1.05, 20.8). The survival for patients diagnosed in the postpartum period was significantly worse than for controls. CONCLUSION: Women diagnosed postpartum had worse survival than those diagnosed during pregnancy and were at significant risk of recurrent disease, particularly if they delivered vaginally. Therefore, pregnant women with cervical cancer should be delivered by cesarean.

Adenocarcinoma↗