RESUMEN

DNA-protein relationships have been studied by numerous methods, but a particular gap in methodology lies in the study of DNA adduct-specific interactions with proteins in vivo, which particularly affects the field of DNA repair. Using the repair of a well-characterized and ubiquitous adduct, the abasic (AP) site, as a model, we have developed a comprehensive method of monitoring DNA lesion-specific recruitment of proteins in vivo over time. We utilized a surrogate system in which a Cy3-labeled plasmid containing a single AP-site was transfected into cells, and the interaction of the labeled DNA with BER enzymes, including APE1, Polß, LIG1, and FEN1, was monitored by immunofluorescent staining of the enzymes by Alexafluor-488-conjugated secondary antibody. The recruitment of enzymes was characterized by quantification of Cy3-Alexafluor-488 co-localization. To validate the microscopy-based method, repair of the transfected AP-site DNA was also quantified at various time points post-transfection using a real time PCR-based method. Notably, the recruitment time kinetics for each enzyme were consistent with AP-site repair time kinetics. This microscopy-based methodology is reliable in detecting the recruitment of proteins to specific DNA substrates and can be extended to study other in vivo DNA-protein relationships in any DNA sequence and in the context of any DNA structure in transfectable proliferating or quiescent cells. The method may be applied to a variety of disciplines of nucleic acid transaction pathways, including repair, replication, transcription, and recombination.

Asunto(s)

Aductos de ADN/metabolismo , ADN Ligasas/metabolismo , ADN Polimerasa beta/metabolismo , Reparación del ADN/fisiología , ADN-(Sitio Apurínico o Apirimidínico) Liasa/metabolismo , Endonucleasas de ADN Solapado/metabolismo , Línea Celular , ADN Ligasa (ATP) , Humanos , Reacción en Cadena de la Polimerasa , Transfección

RESUMEN

AIM: To assess the nutritional status of gynecological cancer patients using scored Patient Generated Subjective Global Assessment (PG-SGA) then compare it with the body mass index (BMI), hemoglobin, serum albumin, and approximate percentage weight lost in last 1 month so as to find any one parameter that can be used in place of the comprehensive assessment tool. MATERIALS AND METHODS: Sixty gynecological cancer patients were assessed for their nutritional status using BMI, serum albumin, hemoglobin, percentage weight lost in last 1 month, and scored PG-SGA. Correlation, sensitivity, specificity, and predictive values of the former four parameters compared to scored PG-SGA were calculated. RESULTS: 88.33% of cases were at risk of or had some degree of malnutrition according to scored PG-SGA. Serum albumin level ≤ 2 g/dl had highest specificity and positive predictive value at 1, whereas percentage weight lost in last month had better overall sensitivity, specificity, and positive and negative predictive values of 0.5833, 0.9444, 0.875, and 0.7727, respectively. The Pearson's correlation coefficient between scored PG-SGA and percentage weight lost in last 1 month was 0.784, highest among all the parameters. CONCLUSION: 88.33% of gynecologic cancer cases had some degree of malnutrition or were at risk of malnutrition. Approximate percentage weight lost in last 1 month, that is, ≥ 5% may be used in place of the comprehensive scored PG-SGA to triage the patients in case the latter is not used for some reason. Severe hypoalbuminemia ≤ 2 g/dl is an indicator of severe malnutrition in gynecologic cancer cases.

RESUMEN

OBJECTIVE: To evaluate the clinical, laboratory, and diagnostic features in women with abdominal tuberculosis that resembled advanced ovarian malignancy. METHODS: A retrospective review of women with abdominal tuberculosis who were managed at GCRI Ahmedabad from 1996 to 2001 was undertaken. RESULTS: Fifteen patients (3.06 %) with suspected ovarian cancer cases, finally diagnosed as abdominal tuberculosis over a 6-year period (1996-2001), are analyzed. During this period, 492 patients were operated for suspected ovarian malignancy. Pre-operatively, ultrasound-guided biopsies were inconclusive in 14 cases and hence, exploratory laparotomy was planned. They underwent laparotomy and biopsy for final diagnosis. Frozen sections-of peritoneal/omental biopsies in 11 cases and ovarian tumour in three cases-were indicative of tuberculosis in all the 14 cases. CONCLUSION: The data of this study indicate that the majority of the cases with peritoneal tuberculosis can be diagnosed intra-operatively through the use of frozen section in conjunction with clinical features. Ascites and high levels of Ca125 do not necessarily indicate that the clinical picture is malignant in reproductive women. Laparoscopic tissue biopsy may be a fundamental tool in the management of such cases to avoid extended surgery.

RESUMEN

OBJECTIVES: To evaluate the clinico-pathological features, surgical procedures and postoperative treatment and their relation to survival in women with granulosa cell tumours. METHODS: Data of 37 women with granulosa cell tumours were collected and reviewed retrospectively. Mann-Whitney test, log rank test and Kaplan-Meier survival analysis were applied appropriately. RESULTS: Thirty-seven women of median age 48.6 years were diagnosed in stage Ia (45.9 %), stage Ic (27 %), stage III (16.2 %) and unstaged (10.8 %). The median follow up was 5 years. Overall survival was 93 % at 5 years. Disease-free survival at 5 years was 63 %. Tumour stage and residual disease were associated with poor prognosis (p < 0.001). Mitotic rate and tumour grade were not of prognostic significance. CONCLUSIONS: Stage of disease and residual disease are valuable prognostic factors. Prospective studies with large sample sizes and long-term follow up are needed to confirm our findings.

RESUMEN

OBJECTIVES: The aim of this retrospective study was to evaluate the behavior and treatment outcomes of uterine carcinosarcomas in relation to their clinical and pathogenic features and to determine the optimal treatment strategy. Secondary objectives were to identify parameters predictive of survival. MATERIALS AND METHODS: The hospital records of all 25 patients of uterine carcinosarcoma operated between 2000 and 2008 in Gujarat cancer research institute, Ahmedabad, were reviewed. Patients who presented with clinical evidence of recurrent disease or those who had incomplete medical records were excluded from our analysis. The status of these patients was updated up to November, 2010. Patients were classified according to the new 2009 FIGO staging system for endometrial carcinoma, to see what difference the assigned stage has on survival with the old treatment strategy. Survival was calculated by Kaplan-Meier method and compared by Log-Rank test. Median survival time was derived with the Brookmeyer 95% confidence interval. For comparison of qualitative data, Chi-Square test and Fisher extract χ(2) were used. RESULTS: Median age of patients was 56 years (range, 36-77 years). Only 36% of patients had stage I at diagnosis and another 36% were stage III. Most of the tumors (56%) were with homologous sarcomatous components and 64% of tumors were high grade (grade 2/3) at diagnosis. Fifty-two percent patients received postoperative adjuvant treatment. Twelve patients had no postoperative treatment: two were lost to follow-up immediately after surgery, four could not receive adjuvant treatment on account of severe medical complications and age factor which could have increased morbidity, and six patients declined treatment. Four of these patients expired within one year of diagnosis, two other within 18 months, and rest were lost to follow-up. The difference in survival of 13 patients who had taken adjuvant treatment was significantly more than the group who had not taken adjuvant therapy (P=0.025). The overall 3-year disease-free survival of 13 patients who had taken adjuvant therapy was 40%. However, these adjuvant treatment modalities had borderline statistical significance on overall survival of patients (P=0.075). The only statistically significant predictor of survival in this study was stage of the disease (P=0.035). CONCLUSIONS: This highly aggressive uterine malignancy warrants comprehensive surgical staging to assess tumor dissemination followed by systematic adjuvant therapy in patients with both early and advanced disease. The value of pelvic Radiotherapy in addition to systemic treatment remains ill-defined. Stage is the significant predictor of survival for the disease. Our results indicate that in this highly aggressive malignancy, further exploration of potential outcome benefits of postoperative treatment, especially chemoradiation, is warranted in larger group of patients after comprehensive surgical staging.

RESUMEN

OBJECTIVE: To evaluate and analyze the results of chemotherapy (EMA-CO [etoposide, methotrexate, actinomycin D-cyclophosphamide, vincristine]) in high-risk gestational trophoblastic neoplasia (GTN). STUDY DESIGN: A total of 97 women with high-risk GTN were evaluated for a period of 13 years (1995-2008). All women received EMA-CO as a first-line chemotherapy. EMA-EP (etoposide, methotrexate, actinomycin and cisplatinum), PVB (cisplatin, vinblastine and bleomycin), and BEP (bleomycin, etoposide and cisplatin) were the chemotherapies used as second-line therapy in women who experienced resistance to primary chemotherapy. Intrathecal methotrexate was given in women with brain metastasis and also as prophylaxis in pulmonary metastasis. Eleven women had brain metastasis and received cranial radiotherapy. The most common toxicity was hematologic. . RESULTS: Of 97 women, 78 (80.4%) were evaluable and 19 (19.6%) were lost to follow-up with incomplete treatment. Of the 78 patients, 6 women developed resistance and had progression of disease. Seven women had died (5 due to disease, 2 due to chemotherapy toxicity). Overall 65 of the 78 (83.3%) women achieved remission. Of the 78 women, 66.7% (52/78) had complete remission with first-line chemotherapy, and an additional 16.6% (13/78) achieved remission with second-line chemotherapy, resulting in a total of 83.3% (65/78) attaining remission. A total of 46% (30/ 65) had follow-up of > 3 years, and 32.4% (21/65) had follow-up of 1-3 years. Three of 9 women with brain metastasis achieved remission. Sixty percent (39/65) resumed normal menstrual function (had remission for at least 2 years). Twelve women became pregnant since the completion of the chemotherapy, with 10 live births of healthy infants without any congenital abnormalities. CONCLUSION: High-risk GTNs are highly curable if properly treated, and patients can anticipate a normal future reproductive outcome. EMA-CO remains the preferred chemotherapy for management.

Asunto(s)

Enfermedad Trofoblástica Gestacional/tratamiento farmacológico , Enfermedad Trofoblástica Gestacional/mortalidad , Neoplasias Uterinas/tratamiento farmacológico , Neoplasias Uterinas/mortalidad , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bleomicina/uso terapéutico , Cisplatino/uso terapéutico , Ciclofosfamida/uso terapéutico , Dactinomicina/uso terapéutico , Resistencia a Antineoplásicos , Etopósido/uso terapéutico , Femenino , Enfermedad Trofoblástica Gestacional/patología , Humanos , India , Metotrexato/uso terapéutico , Metástasis de la Neoplasia , Embarazo , Inducción de Remisión , Estudios Retrospectivos , Neoplasias Uterinas/patología , Vinblastina/uso terapéutico , Vincristina/uso terapéutico

RESUMEN

AIMS AND OBJECTIVE: Over 70% of the cases present in advanced stages of the disease and are associated with poor prognosis and high mortality rates. In many of them, it is difficult to offer definitive treatment as they present in uremia due to associated obstructive uropathy. There are no clear-cut guidelines for performing percutaneous nephrostomy (PCN) in patients of advanced cervical cancer. The results are unpredictable in terms of benefits achieved in these cases. Thus, we evaluated our experiences with PCN in the management of cervical cancer patients presenting with obstructive uropathy. MATERIAL AND METHODS: 15 patients of cervical cancer with obstructive uropathy and deranged renal functions were retrospectively evaluated for the role of PCN in their management RESULTS: PCN was done in 15 patients of advanced cervical cancer. The mean age of patients was 44.5 years. Twelve (80%) patients presented primarily with advanced cervical carcinoma and obstructive uropathy. Three (20%) were already treated. Symptomatic improvement and significant fall of mean serum creatinine value from 7.5 mg% to 0.9 mg% over a period of 1-3 weeks was noted post PCN. Out of 12 patient with primary untreated advanced disease, curative treatment was possible in 3, palliative radiotherapy/chemo-therapy in 7 and only symptomatic treatment in 2 cases, after obstructive uropathy was managed with PCN insertion. Out of 3 already treated patients, 2 were disease free after curative radiotherapy/surgery. PCN was done to prevent permanent kidney damage in them. One patient was defaulter of curative radiotherapy. She had progressive residual disease. Complications like hemorrhage (20%), infection (26%), reinsertion for dislodgment/misplacement (53%), percutaneous leak or perinephric leak (20%), blockage of PCN (33%) were noticed. CONCLUSION: In spite of inherent, albeit manageable complications, PCN is a simple and safe technique. One of the major benefits observed was ability to administer either curative/palliative radiotherapy or chemotherapy in 85% of patients (11 out of 13 with disease). There was no active disease in remaining 2 patients. Therefore, the decision to attempt PCN in carefully selected cervical cancer patients is justified.