Biomedical subjects

T H Ho

Publications and source records attributed to T H Ho.

At least 19 recordsLinked to original sources

PubMed2005

p53 and bcl-2 expression in invasive and pre-invasive uterine papillary serous carcinoma and atrophic endometrium.

INTRODUCTION: Uterine papillary serous carcinoma (UPSC), a high-grade tumour, is known to be associated in some cases with an identifiable intraepithelial neoplasia (IEN) component. Biomarker studies incorporating this latter component are not well documented. One aim of the present study was to compare levels of immunohistochemical (IHC) expression of p53 tumour suppressor gene and bcl-2 oncoprotein between UPSC and IEN, as well as normal endometrium to determine its biologic significance. The other major aim was to determine if these IHC results have any bearing on survival data in this tumour. MATERIALS AND METHODS: An immunoreactivity score was assigned for examination of p53 and bcl-2 expression in a total of 21 cases of UPSC, 9 with an evaluable IEN component and 11 with associated non-neoplastic endometrium. Statistical analysis of IHC results was performed, in addition to correlation with survival data and disease stage. RESULTS: p53 was identified in 16/21 cases of UPSC (76%) and 8/9 cases of IEN (89%), and no cases of normal endometrium. By contrast, bcl-2 was positive in all normal endometria with less expression in UPSC leaving 15/21 (71%) cases positive, and in IEN, leaving 5/9 (55%) of cases positive. Differences in immunoreactive scores for both p53 and bcl-2 between UPSC and benign glands, as well as between IEN and benign glands reached statistical significance with P values of 0.006 and 0.014 for p53, and 0.003 and 0.027 for bcl-2 respectively. There was no statistical significance between values for UPSC and IEN. Cox regression analysis found no statistically significant relationship between patient survival time in early and late stages of disease, and p53 and bcl-2 immunoscores. CONCLUSIONS: The lack of a significant difference between the bcl-2 and p53 values for both UPSC and IEN suggests that these molecular alterations occur at an early stage of tumour pathogenesis. A potential advantage of the use of immunohistochemical markers is their application to routinely processed surgical specimens. In this case, bcl-2 and p53 were applied in UPSC to determine any potential significance, but neither marker proved to be a useful predictor of survival time or disease stage.

Atrophy↗

PubMed2004

Tailoring the field and indication of adjuvant pelvic radiation for patients with FIGO stage Ib lymph nodes-negative cervical carcinoma following radical surgery based on the GOG score--a pilot study.

INTRODUCTION: The traditional indications for adjuvant pelvic radiotherapy (RT) for International Federation of Obstetrics and Gynecology (FIGO) stage Ib1 lymph nodes-negative cervix carcinoma following radical surgery based on histopathological factors, such as deep stromal invasion and lymphovascular space invasion (LVSI), were often inconsistently applied. The perceived risk of relapse was subjectively determined. This pilot study attempts to determine if the treatment outcome will be affected when the indication for RT is based on the Gynecologic Oncology Group (GOG) Risk Score (RS) and the field of adjuvant RT is tailored to the RS. MATERIALS AND METHODS: From 1997 to 1999, 55 patients with FIGO stage Ib1 lymph nodes-negative cervical carcinoma limited to the cervix were prescribed RT following radical surgery, based on their RS, as follows: RS <40, RT is omitted; RS >40 to <120, modified (smaller) field RT; and RS >120, standard field pelvic RT. Their incidence and site of recurrence were compared with a similar cohort of 40 patients who were treated prior to 1997. RESULTS: Prior to 1997, of the 40 patients, 10 patients were given standard field RT. There were 2 (5%) recurrent diseases. The mean duration of follow-up was 61.6 months (range, 1 to 103 months). The RS of 23 of the 30 patients who were not given RT were available. The mean RS was 22 with 5 patients having a score of >40. From 1997 onwards, of the 55 patients, 28 (51%) did not require RT, 13 (23%) were treated with modified (smaller) field RT and 14 (26%) were given standard field RT. There were 2 (3.6%) cases of relapse. The mean duration of follow-up was 36.4 months (range, 5 to 60 months). All patients with a RS of <40 did not suffer any relapse. Their survival outcomes were better when compared to patients who did not have any RT in the GOG Study. CONCLUSIONS: The results of this study indicated that postoperative adjuvant RT given to patients with a high GOG RS of >120, significantly improved their 5-year recurrence rate and disease-free survival, as compared with the similar group of patients who were without adjuvant therapy in the GOG study. Patients with a GOG risk-score of <40 may be safely spared from adjuvant pelvic RT. The current treatment protocol did not compromise the outcome in patients, compared with the use of a less precise treatment protocol in the past.

Adult↗

PubMed2003

A rare case of metastatic ovarian carcinoma originating from primary intrahepatic cholangiocarcinoma. Case report.

BACKGROUND: A rare case of metastatic ovarian carcinoma arising from intrahepatic cholangiocarcinoma is reported and the literature reviewed. CASE: A 49-year-old woman presented with ascites and a left pelvic mass. Optimal debulking surgery was carried out including a segmental resection of segment 5/6 of the liver. Histopathology confirmed an intrahepatic cholangiocarcinoma metastatic to the ovaries and omentum. CONCLUSION: Distinguishing a metastatic tumor from a primary ovarian tumoris critical for appropriate management. A high index of suspicion intraoperatively and subsequent expert pathological review are essential in making the correct diagnosis.

Abdominal Pain↗

PubMed2003

Bowel surgery for epithelial ovarian cancer--an early case series.

OBJECTIVES: The aims of this study were to review our local experience with bowel surgery for epithelial ovarian cancer at the Gynaecological Cancer Centre, KK Women's and Children's Hospital, and to document the outcome of such surgery as well as their complication rates. MATERIALS AND METHODS: The retrospective medical records of 38 patients with epithelial ovarian cancer who underwent surgery including bowel surgery from January 1997 to May 2002 at the Gynaecological Cancer Centre, KK Women's and Children's Hospital, Singapore, were reviewed. RESULTS: Indications for surgery were predominantly debulking of disease. Fifty-eight per cent of patients had primary debulking surgery, 34% had debulking of recurrence and 3% had interval debulking. Only 5% of patients had bowel obstruction as the only indication for surgery. Rectosigmoid resection was the most common bowel operation overall, being performed in 76.3% of patients. The stoma rate for rectosigmoid resection was 61%. The remaining procedures included 7 colectomies, 1 intestinal bypass procedure and 1 intestinal diversion procedure. Optimal debulking (defined as < 1 cm of residual disease) was achieved in the majority (71%). The median operating time was 4 hours. The median blood loss was 1300 mL. The major complication rate was 10.5%. Major complications encountered were as follows: 1 patient (2.6%) had an anastomotic leak, 2 patients (5.3%) had intra-abdominal abscess and 1 patient (2.6%) developed intestinal fistula. Three patients (7.8%) required a re-operation within 30 days. There were 3 deaths (7.8%) within 30 days of surgery. CONCLUSION: Bowel surgery is commonly indicated for epithelial ovarian cancer to facilitate optimal debulking. Such surgery is feasible with acceptable complication rates in our local centre.

Adult↗

PubMed2003

FIGO stage 1B2 cervical carcinoma--the KK Women's and Children's Hospital experience.

INTRODUCTION: The objectives of this review were to document the surgico-pathological characteristics of surgically resected FIGO stage 1B2 cervical carcinoma and to review our overall experience with this disease. MATERIALS AND METHODS: This is a retrospective review of 35 patients diagnosed and treated from September 1990 to November 2001. RESULTS: The median age was 42 years and the mean tumour diameter was 5.1 cm. Majority were squamous cell carcinomas (65.7%), 28.6% were adenocarcinomas and 5.7% were adeno-squamous carcinomas. The primary treatment comprised radical surgery in 77.1%, radiotherapy in 20% and neoadjuvant chemotherapy followed by radical surgery and adjuvant radiotherapy in 2.9%. Significant surgico-pathological features noted were deep stromal invasion (66.7%), lympho-vascular space invasion (55.6%), parametrial involvement (22.2%), positive margins (3.7%) and pelvic node metastases (33.3%). Postoperative radiation was given to 92.6% of the patients who underwent primary surgery, of whom 29% received concurrent chemotherapy. Radiation toxicity was mild with no grade 3 or 4 toxicity documented. For the patients who had surgery, the recurRence rate was 14.8% (11.1% pelvic and 3.7% distant) and the survival rate was 88.9%. For those who had primary radiation, the rate of persistent disease was 28.6%, the distant recurrence rate was 28.6% and the survival rate was 57.1%. CONCLUSION: FIGO stage 1B2 cervical carcinomas are associated with significant rates of adverse surgico-pathological features. The ideal primary treatment is yet to be established and should be determined by prospective randomised trials.

Adult↗

PubMed2003

Endometrioid adenocarcinoma of the uterus: surgico-pathological correlations and role of pelvic lymphadenectomy.

INTRODUCTION: In 1988, FIGO added lymph node surgery to the staging system for endometrial cancer. This change remains controversial to date. From our study we aim to determine the significance of surgico-pathological parameters of endometrioid carcinoma for pelvic nodal metastases and survival, as well as to study the role of pelvic lymphadenectomy in the surgical treatment of this disease. MATERIALS AND METHODS: A retrospective study was conducted in 198 women with endometrioid carcinoma who underwent full surgical staging including pelvic lymphadenectomy. The multiple variant regression analysis and the multi-variant logistic regression analysis were applied in the analysis of relationship. RESULTS: A positive correlation between nodal metastases and grade, myometrial invasion, peritoneal cytology, adnexal involvement, lympho-vascular space involvement and tumour size was found. For survival, significant prognosticators were grade, myometrial invasion, peritoneal cytology, lympho-vascular space involvement, adnexal involvement, associated atypia and pelvic nodal metastases. Thirty-five per cent of the patients had high risk of recurrence based on uterine pathological factors but were node negative. They were spared external beam radiation and its associated morbidities, and were treated with adjuvant vault brachytherapy instead. Six per cent of the patients would have been understaged based on uterine factors alone if pelvic lymphadenectomy had not been done. CONCLUSION: We infer that routine pelvic lymphadenectomy should be considered for all surgically fit patients with endometrioid carcinoma. The accurate staging will allow individualized adjuvant therapy and prevent understaging and overtreatment.

Adult↗

PubMed2002

Identification and characterization of genes involved in the carcinogenesis of human squamous cell cervical carcinoma.

We utilized RT-PCR differential display and cDNA microarrays to identify cellular genes involved in the multi-step carcinogenesis of squamous cell cervical carcinoma. Thirty-eight cervical cancer patients in various stages of the disease and 5 non-cervical cancer patients were studied. Twenty-five cDNA clones were identified and these were subsequently demonstrated to be consistently over-expressed in squamous cell cervical carcinoma biopsies of various FIGO stages. To further evaluate the possible role that these genes may play in the progression of disease, we performed Northern blot analysis and RNA-RNA in situ hybridization studies using cervical cancer biopsies of various FIGO stages. Of particular interest are the 2 clones G32C4B and G30CC that have been identified to be the NADH dehydrogenase 4 gene and the gene that encodes ribosomal protein S12 respectively when compared to sequences available in the GenBank database. Increased expression of these 2 genes were detected in the matched normal tissues collected together with the late FIGO stages of cervical cancer biopsies. In comparison, upregulation of these 2 genes was not detected in cervical squamous epithelium collected from patients admitted for surgery for non-malignant conditions, suggesting that expression of these 2 genes may have altered in the adjacent histopathologically "normal" cervical squamous epithelial tissue from cervical cancer patients. The ribosomal protein S12 and the NADH dehydrogenase 4 genes may therefore be potentially useful as early pre-transformation diagnostic markers for human cervical cancer.

Biomarkers, Tumor↗

PubMed2002

Identification of molecular markers for the early detection of human squamous cell carcinoma of the uterine cervix.

To identify novel cellular genes that could potentially act as predictive molecular markers for human cervical cancer, we employed RT--PCR differential display, reverse Northern and Northern blot analysis to compare the gene expression profiles between squamous cell carcinoma biopsies and adjacent histo-pathological normal epithelium tissues. Twenty-eight cDNA clones were isolated that were demonstrated to be consistently over-expressed in squamous cell cervical cancer biopsies of FIGO stages 1B to 3B. Most importantly, it was observed that, in addition to their over-expression in cancer lesions, some of these genes are upregulated in the presumably histo-pathological normal adjacent tissues. Of particular interest is clone G30CC that has been identified to be the gene that encodes S12 ribosomal protein. When employed for RNA--RNA in situ hybridization experiments, expression of G30CC could be detected in the immature basal epithelial cells of histo-pathological normal tissues collected from cervical cancer patients of early FIGO stages. In comparison, the expression of G30CC was not detected in cervical tissues collected from patients admitted for surgery of non-malignant conditions. These results allow the distinct possibility of employing the ribosomal protein S12 gene as an early molecular diagnostic identifier for the screening of human cervical cancer and a potential target employed for cancer gene therapy trials.

Biomarkers, Tumor↗

PubMed2002

Malignant ovarian germ cell tumors: the KK Hospital experience.

Ovarian germ cell malignancies pose a therapeutic challenge especially amongst young patients. This is a retrospective review of 49 patients treated for such malignancies at KK Women's and Children's Hospital over a 13-year period. The relative proportion of such tumors was 6.2%. Age at presentation ranged from 14 to 51 years (mean 25.4 years). Forty-nine percent of tumors were immature teratomas and 81.6% had stage I disease. All patients had surgery initially and 67.3% required postoperative adjuvant chemotherapy. The patients were followed-up for one to 145 months (mean 51.6 months). All the 87.8% of patients on follow-up are alive and disease-free. There was one recurrence. Five patients had eight successful pregnancies, with no congenital anomalies. Mean duration when menstruation was resumed and regular was 2.5 and 3.5 months, respectively. With combination chemotherapy and conservative surgery, the outlook for patients is excellent, with emphasis on preservation of ovarian function and fertility.

Adolescent↗

PubMed2002

Malignant mixed Mullerian tumours of the uterus--a ten-year experience.

OBJECTIVES: To review the clinico-pathological features of malignant mixed Mullerian tumours of the uterine corpus, their prognosis and treatment outcome. METHODS: A retrospective study of malignant mixed Mullerian tumours of the uterus seen at KK Women's & Children's Hospital from January 1989 to December 1998. RESULTS AND CONCLUSION: Twenty-six patients with mean age of 56.5 years were analysed. Twenty (76.9%) were menopausal. None had previous pelvic irradiation. Vaginal bleeding and uterine enlargement were the commonest presenting symptom and sign. Diagnostic dilatation and curettage obtained the diagnosis in 15 patients. Majority of patients had surgery with adjuvant chemotherapy, while adjuvant radiotherapy was offered only recently. Positive peritoneal washings were significantly associated with advanced disease. There were seven patients with stage I, four with stage II, nine with stage III and four with stage IV disease. There were 17 homologous and nine heterologous tumours. Presence of heterologous stromal components did not influence the stage of the disease. Increasing depth of myometrial invasion was associated with poorer survival. Prognosis of patients with stage III and IV disease were poor, with none surviving to two years. All the patients with stage I disease were still alive at the end of the study period. In conclusion, malignant mixed Mullerian tumours of the uterine corpus are aggressive tumours associated with poor prognosis.

Adolescent↗

PubMed2001

The stress- and abscisic acid-induced barley gene HVA22: developmental regulation and homologues in diverse organisms.

Abscisic acid (ABA) induces the expression of a battery of genes in mediating plant responses to environmental stresses. Here we report one of the early ABA-inducible genes in barley (Hordeum vulgare L.), HVA22, which shares little homology with other ABA-responsive genes such as LEA (late embryogenesis-abundant) and RAB (responsive to ABA) genes. In grains, the expression of HVA22 gene appears to be correlated with the dormancy status. The level of HVA22 mRNA increases during grain development, and declines to an undetectable level within 12 h after imbibition of non-dormant grains. In contrast, the HVA22 mRNA level remains high in dormant grains even after five days of imbibition. Treatment of dormant grains with gibberellin (GA) effectively breaks dormancy with a concomitant decline of the level of HVA22 mRNA. The expression of HVA22 appears to be tissue-specific with the level of its mRNA readily detectable in aleurone layers and embryos, yet undetectable in the starchy endosperm. The expression of HVA22 in vegetative tissues can be induced by ABA and environmental stresses, such as cold and drought. Apparent homologues of this barley gene are found in phylogenetically divergent eukaryotic organisms, including cereals, Arabidopsis, Caenorhabditis elegans, man, mouse and yeast, but not in any prokaryotes. Interestingly, similar to barley HVA22, the yeast homologue is also stress-inducible. These observations suggest that the HVA22 and its homologues encode a highly conserved stress-inducible protein which may play an important role in protecting cells from damage under stress conditions in many eukaryotic organisms.

Abscisic Acid↗

PubMed2001

Dissection of abscisic acid signal transduction pathways in barley aleurone layers.

Abscisic acid (ABA) induces genes that are highly expressed during late embryogenesis, but suppresses gibberellin (GA)-responsive genes essential for seed germination and seedling growth. Promoter elements necessary and sufficient for ABA up- and down-regulation of gene expression have been previously defined in barley aleurone layers. We have studied the effect of a protein phosphatase 2C, ABI1, an ABA-inducible protein kinase, PKABA1, and a transcription factor, VP1, on ABA action in a barley aleurone transient expression system. The observations have allowed us to dissect ABA signal transduction pathways leading to either induction or suppression of gene expression. The ABA induction of embryogenesis genes is highly inhibited in the presence of a mutated protein phosphatase 2C, encoded by the abi1-1 dominant mutant gene that is known to block ABA responses in Arabidopsis. However, the abi1-1 gene product has no effect on the ABA suppression of a GA-responsive alpha-amylase gene. On the other hand, PKABA1 suppresses the expression of alpha-amylase genes, but has little effect on ABA up-regulated genes. Therefore, it appears that ABA induction and suppression follow two separate signal transduction pathways with the former inhibited by ABI1 and the latter modulated by PKABA1. The presence of VP1 enhances the ABA induction of late embryogenesis genes, but also suppresses germination specific genes. A schematic model based on these observations is presented to explain the effect of these regulatory proteins on ABA-mediated gene expression.

Abscisic Acid↗

PubMed2001

The salt stress-inducible protein kinase gene, Esi47, from the salt-tolerant wheatgrass Lophopyrum elongatum is involved in plant hormone signaling.

Protein kinases play a central role in signal transduction in all organisms and to study signal transduction in response to salt stress we have identified and characterized a gene encoding a protein kinase that is induced by salt stress and abscisic acid (ABA) in the salt-tolerant wild wheatgrass Lophopyrum elongatum (Host) A. Love. The product of the early salt stress-induced gene, Esi47, was found to belong to the "novel Arabidopsis protein kinase" group of plant serine/threonine protein kinases. Transient gene expression assays in barley aleurone tissue showed Esi47 to suppress the gibberellin induction of the barley low-pI alpha-amylase gene promoter, thus providing evidence for the role of this protein kinase gene in plant hormone signaling. Esi47 contains a small upstream open reading frame in the 5'-untranslated region of its transcript that is implicated in mediating the repression of the basal level of the gene expression and in regulating the ABA inducibility of the gene, as shown in the transient gene expression assay in maize callus. Three Arabidopsis homologs of Esi47 were identified, and different members of this clade of genes showed differential patterns of regulation by salt stress and ABA in Arabidopsis roots and leaves. At least one of the Arabidopsis homologs contains a small open reading frame in its 5'-untranslated region, indicating that the unusual regulatory mechanism identified in Esi47 may be widely conserved.

5' Untranslated Regions↗

PubMed2001

A comparative study of cervical cytology, colposcopy and PCR for HPV in female sex workers in Singapore.

This study examined the prevalence of human papillomavirus (HPV) infection in a cohort of female sex workers in Singapore. HPV infection was diagnosed by clinical examination, Papanicolaou (Pap) smears, histology and polymerase chain reaction (PCR). One hundred and eighty-seven female sex workers who came for their routine medical screening were enrolled into the study. PCR was positive for HPV in 27 (14.4%), 20 of these had a single HPV type detected, while 7 had multiple types of HPV detected. The most common HPV types identified were types 16, 58 and 18. In conclusion, HPV infection is moderately prevalent among sex workers as tested by PCR, but routine screening with Pap smears does not appear to be a sensitive method of diagnosis for HPV infection.

Adult↗

PubMed2001

Gibberellin/abscisic acid antagonism in barley aleurone cells: site of action of the protein kinase PKABA1 in relation to gibberellin signaling molecules.

The antagonism between gibberellins (GA) and abscisic acid (ABA) is an important factor regulating the developmental transition from embryogenesis to seed germination. In barley aleurone layers, the expression of genes encoding alpha-amylases and proteases is induced by GA but suppressed by ABA. It has been shown that an ABA-induced protein kinase, PKABA1, mediates the ABA suppression of alpha-amylase expression. Using a barley aleurone transient expression system, we have now localized the site of action of PKABA1 relative to other signal transduction components governing the expression of alpha-amylase. The expression of alpha-amylase can be transactivated by the transcription factor GAMyb, which is itself induced by GA. A truncated GAMyb containing the DNA binding domain but lacking the transactivation domain prevents the GA induction of alpha-amylase, further supporting the notion that GAMyb mediates the GA induction of alpha-amylase expression. Although ABA and PKABA1 strongly inhibit the GA induction of alpha-amylase, they have no effect on GAMyb-transactivated alpha-amylase expression. Using a GAMyb promoter--beta-glucuronidase construct, we also show that both ABA and PKABA1 repress the GA induction of GAMyb. In the slender mutant, GAMyb and alpha-amylase are highly expressed, even in the absence of GA. However, this constitutive expression can still be inhibited by ABA, PKABA1, or an inhibitor of cGMP synthesis. On the basis of these observations, we suggest that PKABA1 acts upstream from the formation of functional GAMyb but downstream from the site of action of the Slender gene product. Because PKABA1 inhibits the GA induction of the GAMyb promoter--beta-glucuronidase construct, it appears that at least part of the action of PKABA1 is to downregulate GAMyb at the transcriptional level.

Abscisic Acid↗

PubMed2001

A clinical review of granulosa cell tumours of the ovary cases in KKH.

INTRODUCTION: Granulosa cell tumour (GCT) represents the largest group of sex-cord stromal tumours and comprises 1.5-3% of ovarian malignancy. The aim is to determine the incidence of the disease, study the profile of local patients, and assess the use of imaging studies in the diagnosis of the tumour. MATERIAL AND METHODS: Clinical records of 19 patients diagnosed with GCT between October 1988 and July 1997 in Kandang Kerbau Hospital (KKH) were reviewed. RESULTS: GCT accounts for 3.5% of ovarian malignancy (54 out of 1552) in Singapore, of which 94.7% are adult GCT. In our study, patients are mainly peri/postmenopausal women (63.2%) in their 50s who experience post-menopausal bleeding. There is a high incidence of association with endometrial hyperplasia (40%). Ultrasound scans are able to predict the size and involvement of the tumour rather accurately. In our study sample, 13 patients (68.4%) presented with Stage 1 of the disease, none with Stage 2, 1 with Stage 3 (5.3%) and none with Stage 4. The other 5 patients (26.3%) were unstaged. Only one patient required adjuvant chemotherapy. CONCLUSION: The local data with regards to GCT is congruent with those found in foreign literature. However, in our study, there were no patients with recurrence whereas GCTs are known to be late recurring in up to 20% of patients 10-20 years after diagnosis. This is probably attributed to the relatively short period of follow-up in this study. Thus, despite the fact that there is no evidence of recurrence of disease in our current study, we still recommend a vigilant follow-up protocol on all patients as literature has proven that with early detection of recurrences, it is possible to achieve complete cure.

Adult↗

PubMed2001

Vulvar cancer--what do we know about our patients?

INTRODUCTION: Vulvar cancer is uncommon in Singapore and to date there have been no local reports on this rare cancer. This is a descriptive study that aims to evaluate our patients' profiles, their management and their outcomes. MATERIALS AND METHODS: Between January 1981 and December 1998, there were 35 patients with vulvar cancer treated at KK Women's and Children's Hospital. The case records of these patients were reviewed. Survival was calculated using the Kaplan-Meier method. RESULTS: The modal age at diagnosis was 74.0 years (range 17.0-89.0 years). Chinese patients accounted for 88% of the study group, Malays for 6%, Indians for 3% and other races made up 3% of the study group. The most common presenting symptom was an ulcer or lump (83.8%). Squamous cell carcinoma was the most common histological type (80.0%). Vulvar intraepithelial neoplasia III was found in 20% of the cases. There were five patients with other lower genital tract malignancies. Surgery was the most common treatment modality and wound breakdown was the most common complication. The overall five year survival was 75.9%. For stage 1&2 disease, the five year survival was 90.0%. For stage 3&4 disease, the five year survival was 26.0%. CONCLUSION: The rarity of vulvar cancer makes it best treated in a tertiary centre. There is a definite survival advantage in early diagnosis and treatment of vulvar cancer. Lymph node surgery was associated with a longer operating time and a higher chance of wound breakdown.

Female↗

PubMed2000

Parkin is associated with actin filaments in neuronal and nonneural cells.

Inactivating mutations of the gene encoding parkin are responsible for autosomal recessive juvenile parkinsonism (AR-JP). However, little information is known about the function and distribution of parkin. We generated antibodies to two different peptides of parkin. By Western blot analysis and immunohistochemistry, we found that parkin is a 50-kd protein that is expressed in neuronal processes and cytoplasm of selected neurons in the basal ganglia, midbrain, cerebellum, and cerebral cortex. Unlike ubiquitin and alpha-synuclein, parkin labeling was not found in Lewy bodies of four sporadic Parkinson disease brains. Parkin was colocalized with actin filaments but not with microtubules in COS1 kidney cells and nerve growth factor-induced PC12 neurons. These results point to the importance of the cytoskeleton and associated proteins in neurodegeneration.

Actin Cytoskeleton↗