Sentinel lymph node pathological ultrastaging: Final outcome of the Sentix prospective international study in patients with early-stage cervical cancer.

OBJECTIVE: To report the outcome of SLN staging in the SENTIX international prospective trial of SLN biopsy in patients with cervical cancer with an intensive ultrastaging protocol and central quality control and to evaluate how the intensity of pathological assessment correlates with metastatic detection rate in SLNs. METHODS: Eligible were patients with stages T1a1/LVSI+ to T1b2 (<4 cm, ≤2 cm for fertility sparing), common tumor types, no suspicious lymph nodes on imaging, and bilateral SLN detection. SLNs were examined intraoperatively and processed by an intensive protocol for ultrastaging (paraffin blocks sectioned completely in 150-µm intervals/levels). SLNs from each site were submitted for central quality control. RESULTS: In the SENTIX SLN study, 647 out of 733 enrolled patients underwent SLN ultrastaging, identifying 12.5% (81/647) with node positive, N1 cases. Intraoperative detection revealed metastases in 56.8% (46/81) of these cases, categorized into macrometastases (83.7%), micrometastases (26.3%), and isolated tumor cells (9.1%). Ultrastaging identified additional metastatic involvement in 43.2% (35/81) of patients, with detailed sectioning revealing metastases (MAC/MIC) at first level in 20 cases (24.7%), at levels 2-4 in 9 cases (11.1%), and at level ≥5 in 6 cases (7.4%). CONCLUSION: SLN ultrastaging detects additional 43% of N1 (MAC/MIC) in patients with negative LNs by imaging and intraoperative pathological assessment. The detection rate of positive SLN correlates with the intensity (number of levels) of ultrastaging. Examination of four levels from paraffin blocks, which detects >90% of patients with N1, is a reasonable compromise for an international standard for ultrastaging. STUDY REGISTRATION: NCT02494063 (ClinicalTrials.gov).

Lymphovascular Space Invasion in Early-Stage Endometrial Cancer (LySEC): Patterns of Recurrence and Predictors. A Multicentre Retrospective Cohort Study of the Spain Gynecologic Oncology Group.

The main aim is to compare oncological outcomes and patterns of recurrence of patients with early-stage endometrioid endometrial cancer according to lymphovascular space invasion (LVSI) status. The secondary objective is to determine preoperative predictors of LVSI. We performed a multicenter retrospective cohort study. A total of 3546 women diagnosed with postoperative early-stage (FIGO I-II, 2009) endometrioid endometrial cancer were included. Co-primary endpoints were disease-free survival (DFS), overall survival (OS), and pattern of recurrence. Cox proportional hazard models were used for time-to-event analysis. Univariate and multivariate logistical regression models were employed. Positive LVSI was identified in 528 patients (14.6%) and was an independent prognostic factor for DFS (HR 1.8), OS (HR 2.1) and distant recurrences (HR 2.37). Distant recurrences were more frequent in patients with positive LVSI (78.2% vs. 61.3%, p < 0.01). Deep myometrial invasion (OR 3.04), high-grade tumors (OR 2.54), cervical stroma invasion (OR 2.01), and tumor diameter ≥ 2 cm (OR 2.03) were independent predictors of LVSI. In conclusion, in these patients, LVSI is an independent risk factor for shorter DFS and OS, and distant recurrence, but not for local recurrence. Deep myometrial invasion, cervical stroma invasion, high-grade tumors, and a tumor diameter ≥ 2 cm are independent predictors of LVSI.

DNA-Binding Properties of Bis-N-substituted Tetrandrine Derivatives.

A series of bis-N-substituted tetrandrine derivatives carrying different aromatic substituents attached to both nitrogen atoms of the natural alkaloid were studied with double-stranded model DNAs (dsDNAs) to examine the binding properties and mechanism. Variable-temperature molecular recognition studies using UV-vis and fluorescence techniques revealed the thermodynamic parameters, ΔH, ΔS, and ΔG, showing that the tetrandrine derivatives exhibit high affinity toward dsDNA (K ≈ 105-107 M-1), particularly the bis(methyl)anthraquinone (BAqT) and bis(ethyl)indole compounds (BInT). Viscometry experiments, ethidium displacement assays, and molecular modeling studies enabled elucidation of the possible binding mode, indicating that the compounds exhibit a synergic interaction mode involving intercalation of one of the N-aryl substituents and interaction of the molecular skeleton in the major groove of the dsDNA. Cytotoxicity tests of the derivatives with tumor and nontumor cell lines demonstrated low cytotoxicity of these compounds, with the exception of the bis(methyl)pyrene (BPyrT) derivative, which is significantly more cytotoxic than the remaining derivatives, with IC50 values against the LS-180, A-549, and ARPE-19 cell lines that are similar to natural tetrandrine. Finally, complementary electrochemical characterization studies unveiled good electrochemical stability of the compounds.

Chylous Ascites Secondary to Retroperitoneal Para-Aortic Lymphadenectomy: A Case Report.

Chylous ascites is caused by an accumulation of lymphatic fluid in the peritoneal cavity secondary to a rupture or obstruction of the abdominal lymphatic ducts. It has a milky appearance and is rich in triglycerides. The most frequent etiologies are neoplasms, liver cirrhosis, and ruptured lymphatic vessels after abdominal surgery. Clinically, it manifests as abdominal distention and increased abdominal girth. The presence of triglycerides in ascites fluid is the most useful diagnostic criterion. Treatment consists of a high-protein diet with fat restriction and medium-chain triglyceride supplements. Surgery is reserved for refractory cases. We present the case of a 66-year-old patient with a diagnosis of chylous ascites secondary to retroperitoneal lymphadenectomy.

Fertility sparing treatment in patients with endometrial cancer (FERT-ENC): a multicentric retrospective study from the Spanish Investigational Network Gynecologic Oncology Group (SPAIN-GOG).

OBJECTIVE: The primary objective was to evaluate the response rate of conservative treatment for endometrial cancer, and the secondary objective was to assess oncological, fertility and obstetric outcomes in patients who underwent fertility preservation treatment. MATERIAL AND METHODS: This multicentre, observational, retrospective study evaluated endometrial cancer patients who underwent fertility-sparing treatment in Spanish centres between January 2010 and January 2020. Seventy-three patients with stage IA endometrioid adenocarcinoma of the uterus were included in the study. RESULTS: The levonorgestrel intrauterine device (LNG-IUD) was the most common fertility-sparing treatment (53.4%), followed by megestrol acetate (20.5%) and medroxyprogesterone acetate (16.4%). During the 24-month follow-up period, the rate of complete response to fertility-sparing management was 74% (n = 54), and 8.2% (n = 6) of patients presented a partial response. Additionally, 13 (17.8%) patients presented with persistent disease and six (8.2%) relapsed after response. The LNG-IUD was associated with a higher complete response rate than the other methods (87.2 vs. 58.8%; p = 0.01). Surgical treatment (at least hysterectomy) was performed in 44 (60.3%) patients as the end of fertility-sparing treatment. Four (5.5%) patients presented relapse after surgery, associated with final FIGO stage III (p = 0.036), myometrial invasion > 50% (p = 0.018) and final tumour grade 2-3 (p = 0.018). The mean follow-up period was 57.8 (range 6-159) months. The 5-year relapse-free survival and overall survival rates were 92.6% [95% CI (81.3, 97.2)] and 93.5% [95% CI (80.7, 97.9)], respectively. During follow-up, three patients (4.1%) died of the disease after completion of surgical treatment. Up to 50.7% of patients included in the study attempted to get pregnant. Of these, the rate of pregnancy was 81.1% (n = 30/37), and reproductive techniques were used for this purpose in 78.4% of cases. CONCLUSIONS: Fertility-sparing management presented a high response rate in patients with endometrial cancer. LNG-IUD was associated with a better response rate compared to the other treatment options. Moreover, in patients using this management method, pregnancy could be achieved using reproductive techniques.

Role of hysteroscopy during conservative management of atypical endometrial hyperplasia and early-stage endometrial cancer in patients who desire pregnancy.

Twenty-five percent of cases of endometrial cancer appear in women with unfulfilled reproductive desires. An adequate selection of patients and a close hysteroscopic follow-up to monitor the endometrial response to the levonorgestrel-releasing intrauterine system (LNG-IUS) may be a valid and safe option for these patients. This is a case series and review of the literature study. We included eight patients diagnosed of complex endometrial hyperplasia with atypia (CEHA) or stage 1AG1 well-differentiated endometrial cancer without myometrial invasion who desired to get pregnant and opted for a conservative treatment. Follow-up was performed with hysteroscopy and directed biopsy at 3, 6 and 12 months. Of the 854 cases of complex endometrial hyperplasia with atypia (CEHA)/endometrial cancer were diagnosed, 2.3% were candidates for conservative management. We obtained a favourable regression of 71.2% at 6 months and 57% at one year with hormonal treatment. Conservative treatment in complex endometrial hyperplasia with atypia (CEHA)/low-grade endometrial cancer in reproductive age patients with a strong desire for pregnancy is feasible.

Uterine Primitive Neuroectodermal Tumor.

Uterine primitive neuroectodermal tumors (PNETs) are rare entities, with only around 70 cases published in the literature. Most of them are diagnosed in advanced stages with rapid progression and poor prognosis. Herein, we present a case of a 71-year-old patient with postmenopausal metrorrhagia and an ultrasound finding of endometrial thickening. The pathological diagnosis after an endometrial biopsy showed PNET. In the study of extension, possible distant dissemination with infiltration of the sigmoid and liver was observed. Chemotherapy treatment was proposed, but not begun due to the rapid progression of the disease. Four months after the initial diagnosis, the patient died of multiple organ failure. While there is no optimal chemotherapy treatment regimen for PNET, some studies have reported encouraging results. It is necessary to publish more studies emphasizing the follow-up and survival of the disease to establish which may be the best treatment option and thus improve the current poor prognosis.

Post-Conization FIGO stage IA1 squamous cell cervical carcinoma; is hysterectomy necessary?

OBJECTIVE: To compare and evaluate the results and suitability of two different approaches to the treatment of post-conization International Federation of Gynaecology and Obstetrics (FIGO) stage IA1 cervical carcinoma: a more radical approach, directly scheduling a second surgery versus a more conservative one, which consists of performing a cotest (PAP plus HPV-test) in a follow-up visit and deciding whether to apply a second surgery on the basis of the results. STUDY DESIGN: Retrospective descriptive study including 144 cases of stage IA1 cervical carcinoma diagnosed after a loop electrosurgical excisional procedure (conization), between 1987 and 2019 in the Mother-and-Child University Hospital of Gran Canaria (Spain). Selected patients were split into two groups for analysis: patients directly undergoing a second surgical intervention (hysterectomy or re-conization) after diagnosis and patients who were followed-up before making a decision whether to schedule a second surgery or continue to follow-up. RESULTS: 75% of women directly receiving a second surgical intervention (no post-conization follow-up) underwent hysterectomy, while 25% underwent re-conization. Histological outcomes from hysterectomized patients showed 65% negative results for intraepithelial lesions, 9% low-grade squamous intraepithelial lesions (LSIL), 16% high-grade squamous intraepithelial lesions (HSIL) and only 10.5% confirmed invasive lesions: hysterectomy complication rate was 7%. Histological studies from women subjected to re-conization showed 32% negative results, 37% LSIL, 5% HSIL and 26% malignancy. In the group of patients who were followed-up after diagnosis, 8.8% needed a second intervention; none of them showed negative histological results, while 100% hysterectomized and 25% patients with re-conization showed HSIL. No unnecessary hysterectomy procedures were conducted in this group. HPV-16 was the most common genotype in both groups. CONCLUSION: Conization proved to be a suitable alternative to hysterectomy as a treatment for post-conization stage IA1 cervical cancer. Our results showed that 65% hysterectomy procedures conducted without previously monitoring for residual disease corresponded to negative results and were therefore, unnecessary. We conclude that confirmation of the presence of residual disease by using cotest is essential to make a decision on further treatment and that a conservative management is often possible and, in our opinion, preferable.

Lower-Limb Lymphedema after Sentinel Lymph Node Biopsy in Cervical Cancer Patients.

BACKGROUND: To prospectively assess LLL incidence among cervical cancer patients treated by uterine surgery complemented by SLN biopsy, without PLND. METHODS: A prospective study in 150 patients with stage IA1-IB2 cervical cancer treated by uterine surgery with bilateral SLN biopsy. Objective LLL assessments, based on limb volume increase (LVI) between pre- and postoperative measurements, and subjective patient-perceived swelling were conducted in six-month periods over 24-months post-surgery. RESULTS: The cumulative incidence of LLL at 24 months was 17.3% for mild LLL (LVI 10-19%), 9.2% for moderate LLL (LVI 20-39%), while only one patient (0.7%) developed severe LLL (LVI > 40%). The median interval to LLL onset was nine months. Transient edema resolving without intervention within six months was reported in an additional 22% of patients. Subjective LLL was reported by 10.7% of patients, though only a weak and partial correlation between subjective-report and objective-LVI was found. No risk factor directly related to LLL development was identified. CONCLUSIONS: The replacement of standard PLND by bilateral SLN biopsy in the surgical treatment of cervical cancer does not eliminate the risk of mild to moderate LLL, which develops irrespective of the number of SLN removed.

Squamous Cell Carcinoma Arising From a Mature Cystic Teratoma of the Ovary: A Case Report.

Germ cell tumors represent 20-25% of ovarian tumors, and 95% of them are benign. The most frequent type is the mature benign teratoma (dermoid cysts). The proportion of cases in which malignancy occurs is 0.17-2%. Seventy-five percent to 90% of malignancies are squamous cell carcinomas (SCC). We present a case of squamous cell carcinoma originating from a mature cystic teratoma that was diagnosed after intraoperative pathology study in a 64-year-old woman who consulted for an adnexal tumor causing abdominal pain. Laparoscopic surgery was scheduled, describing an enlarged right ovary (13 cm) which was included in the ipsilateral broad ligament and adhered to the posterior aspect of the uterus in its distal third as well as the rectum. It was converted to laparotomy and we performed a hysterectomy + double anexectomy + omentectomy + resection of sigma with end-to-end anastomosis after intraoperative pathological study reported for malignancy compatible with squamous cell carcinoma. It was labeled as FIGO III stage. Chemotherapy was decided as adjuvant therapy with carboplatin + paclitaxel (Carbo-Taxol) scheme. We review the existing literature to provide evidence on a rare pathology with important repercussions for our patients.

Two Patients With Meigs' Syndrome and Elevated Serum CA-125: A Case Report.

Patients with Meigs' syndrome and elevated serum CA-125 are not frequently reported. A 59-year-old woman and a 48-year-old woman sought help because of progressive shortness of breath caused by pleural effusion. The presence of a pelvic mass was noted in both the patients and was thought to be the cause of the effusion. Both patients had elevated serum CA-125, which raised the possibility of malignancy. After complete resection of the tumors, the pathologic reports confirmed a benign and a low-grade malignant ovarian neoplasia, respectively. We comment on the outcome and follow-up of these two cases and briefly review Meigs' syndrome.

Sentinel lymph node mapping and intraoperative assessment in a prospective, international, multicentre, observational trial of patients with cervical cancer: The SENTIX trial.

BACKGROUND: SENTIX (ENGOT-CX2/CEEGOG-CX1) is an international, multicentre, prospective observational trial evaluating sentinel lymph node (SLN) biopsy without pelvic lymph node dissection in patients with early-stage cervical cancer. We report the final preplanned analysis of the secondary end-points: SLN mapping and outcomes of intraoperative SLN pathology. METHODS: Forty-seven sites (18 countries) with experience of SLN biopsy participated in SENTIX. We preregistered patients with stage IA1/lymphovascular space invasion-positive to IB2 (4 cm or smaller or 2 cm or smaller for fertility-sparing treatment) cervical cancer without suspicious lymph nodes on imaging before surgery. SLN frozen section assessment and pathological ultrastaging were mandatory. Patients were registered postoperatively if SLN were bilaterally detected in the pelvis, and frozen sections were negative. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02494063). RESULTS: We analysed data for 395 preregistered patients. Bilateral detection was achieved in 91% (355/395), and it was unaffected by tumour size, tumour stage or body mass index, but it was lower in older patients, in patients who underwent open surgery, and in sites with fewer cases. No SLN were found outside the seven anatomical pelvic regions. Most SLN and positive SLN were localised below the common iliac artery bifurcation. Single positive SLN above the iliac bifurcation were found in 2% of cases. Frozen sections failed to detect 54% of positive lymph nodes (pN1), including 28% of cases with macrometastases and 90% with micrometastases. INTERPRETATION: SLN biopsy can achieve high bilateral SLN detection in patients with tumours of 4 cm or smaller. At experienced centres, all SLN were found in the pelvis, and most were located below the iliac vessel bifurcation. SLN frozen section assessment is an unreliable tool for intraoperative triage because it only detects about half of N1 cases.

Central Pathology Review in SENTIX, A Prospective Observational International Study on Sentinel Lymph Node Biopsy in Patients with Early-Stage Cervical Cancer (ENGOT-CX2).

The quality of pathological assessment is crucial for the safety of patients with cervical cancer if pelvic lymph node dissection is to be replaced by sentinel lymph node (SLN) biopsy. Central pathology review of SLN pathological ultrastaging was conducted in the prospective SENTIX/European Network of Gynaecological Oncological Trial (ENGOT)-CX2 study. All specimens from at least two patients per site were submitted for the central review. For cases with major or critical deviations, the sites were requested to submit all samples from all additional patients for second-round assessment. From the group of 300 patients, samples from 83 cases from 37 sites were reviewed in the first round. Minor, major, critical, and no deviations were identified in 28%, 19%, 14%, and 39% of cases, respectively. Samples from 26 patients were submitted for the second-round review, with only two major deviations found. In conclusion, a high rate of major or critical deviations was identified in the first round of the central pathology review (28% of samples). This reflects a substantial heterogeneity in current practice, despite trial protocol requirements. The importance of the central review conducted prospectively at the early phase of the trial is demonstrated by a substantial improvement of SLN ultrastaging quality in the second-round review.

Role of Race/Ethnicity, Language, and Insurance in Use of Cervical Cancer Prevention Services Among Low-Income Hispanic Women, 2009-2013.

INTRODUCTION: Hispanic women in the United States have an elevated risk of cervical cancer, but the existing literature does not reveal why this disparity persists. METHODS: We performed a retrospective cohort analysis of 17,828 low-income women aged 21 to 64 years seeking care at Oregon community health centers served by a hosted, linked electronic health record during 2009 through 2013. We assessed the odds of having had Papanicolaou (Pap) tests and receiving human papillomavirus (HPV) vaccine, by race/ethnicity, insurance status, and language. RESULTS: Hispanic women, regardless of pregnancy status or insurance, had greater odds of having had Pap tests than non-Hispanic white women during the study period. English-preferring Hispanic women had higher odds of having had Pap tests than Spanish-preferring Hispanic women (OR, 2.08; 95% confidence interval [CI], 1.63-2.66) but lower odds of having received HPV vaccination (OR, 0.21; 95% CI, 0.12-0.38). Uninsured patients, regardless of race/ethnicity, had lower odds of HPV vaccine initiation than insured patients did. Once a single dose was received, there were no significant racial/ethnic differences in vaccine series completion. CONCLUSION: In this sample of low-income women seeking care at Oregon community health centers, we found minimal racial/ethnic disparities in the receipt of cervical cancer prevention services. Inequities by insurance status, especially in the receipt of HPV vaccine, persist. Community health center-based care may be a useful model to address racial/ethnic disparities in prevention, but this model would need further population-wide study.

Synthesis, spectroscopic, physicochemical and structural characterization of tetrandrine-based macrocycles functionalized with acridine and anthracene groups: DNA binding and anti-proliferative activity.

In this work, we report on the synthesis of two new mono-alkylated tetrandrine derivatives with acridine and anthracene units, MAcT and MAnT. The compounds were fully characterized by physicochemical techniques and single-crystal X-ray diffraction analysis. In addition, both derivatives were studied as nucleotide receptors and double-stranded DNA binders in aqueous phosphate buffer at pH = 7.2 using UV-vis and fluorescence spectroscopy. According to the molecular recognition studies, MAcT and MAnT exhibit high affinity (K ∼ 105 M-1) and selectivity for ds-DNA, presumably in an intercalation mode. Finally, the anti-proliferative effects of the tetrandrine derivatives on different cancer cell lines were explored, revealing promising activities. Particularly, the mono-anthracene tetrandrine derivative MAnT showed an IC50 of 2.74 µg/mL on the HeLa cervical cancer cell line, representing a value 3.3 times smaller than that obtained for unsubstituted tetrandrine. Examination of the cytotoxic effects on the HeLa cell line by inverted microscopy suggests that the cell death mechanism consists basically in apoptosis. The molecular modelling of three ds-DNA-MAcT complexes, suggested that the macrocycles may use an intercalation binding mode towards DNA. MAcT is predicted to bind into the major groove of the ds-DNA providing non-covalent interactions such as electrostatic, van der Waals and hydrophobic interactions that lead to selectivity. Overall experimental data supports the mode of action of MAnT and MAcT as cytotoxic compounds against cancer cell lines via a DNA interaction mechanism.

[Matricaria chamomilla (aqueous extract) improves atopic dermatitis-like lesions in a murine model]. / Matricaria chamomilla (extracto acuoso) induce mejoría en lesiones tipo-dermatitis atópica en un modelo murino.

BACKGROUND: Matricaria Chamomilla L. (Mch), popularly known as chamomile, has been used for centuries as an herbolary remedy due to its broad clinical spectrum. The aim of this study was to evaluate the effect of Mch associated to a vehicle with emollient function in induced atopic dermatitis (AD)-like lesions in a murine model. METHODS: AD was induced with dinitrochlorobenzene on 12 male seven-week old BALB/c mice. Animals were divided in three groups (control, GC; control negative, GCN; and experimental, GE). Liquid petrolatum was applied to the GCN and liquid petrolatum with aqueous extract of Mch at 7% to the GE. Induction and evolution of the lesions were verified by biopsy at 2nd and 6th week. Evaluation of peripheral blood cells to correlate inflammatory cells was made as well at the same weeks. Lesions were clinically evaluated at 2nd, 4th and 6th week. Scratching was monitored according to the observation methodology of Kobayashi et al. RESULTS: Mch aqueous extract associated to a vehicle with emollient function improves atopic dermatitis-like lesions after two weeks.

INTRODUCCIÓN: Matricaria chamomilla L. (Mch), conocida popularmente como manzanilla, ha sido utilizada por cientos de años como remedio herbolario debido a su amplio espectro en cuanto a sus usos clínicos. El objetivo de este trabajo fue evaluar el efecto de Mch asociada a un vehículo con función emoliente como tratamiento de lesiones tipo-dermatitis atópica (DA) en un modelo murino. MÉTODOS: se indujo DA con dinitroclorobenceno a 12 ratones BALB/c macho de siete semanas de edad, divididos en tres grupos (control, GC; control negativo, GCN y; experimental, GE). Se aplicó petrolato líquido al GCN y petrolato líquido con extracto acuoso de Mch al 7% al GE durante cuatro semanas. La inducción y evolución de las lesiones se corroboraron por biopsia a las dos y seis semanas, analizando sangre periférica en búsqueda de células inflamatorias en los mismos tiempos. Las lesiones fueron evaluadas clínicamente a las dos, cuatro y seis semanas. El rascado se evaluó de acuerdo a la metodología de observación de Kobayashi et al. RESULTADOS: el extracto acuoso liofilizado de Mch asociado a un vehículo con función emoliente demostró mejoría del aspecto de las lesiones tipo DA después de dos semanas.

Targeting Metabolic Remodeling in Triple Negative Breast Cancer in a Murine Model.

Background: Chemotherapy is the backbone of systemic treatment for triple negative breast cancer (TNBC), which is one of the most relevant breast cancers molecular types due to the ability of tumor cells to develop drug resistance, highlighting the urgent need to design newer and safer drug combinations for treatment. In this context, to overcome tumor cell drug resistance, we employed a novel combinatorial treatment including Doxorubicin, Metformin, and Sodium Oxamate (DoxMetOx). Such pharmacological combination targets indispensable hallmarks of cancer-related to aerobic glycolysis and DNA synthesis. Materials and Methods: Thirty-five female nude mice were transplanted subcutaneously with MDA-MB-231 triple negative human cancer cell line. Once tumors were visible, mice were treated with doxorubicin, metformin, oxamate or all possible pharmacologic combinations. Treatments were administered daily for 15 days and tumors were measured by calipers every day. MicroPET images were taken in three different occasions, basal state, in the middle of the treatment, and at the end of treatment. Western blot analyses, qRT-PCR, flow cytometry, and cytotoxicity assays were performed to elucidate the mechanism of cell death promoted by the drugs in vitro. Results: In this work we assessed the proof of concept of metabolic correction in solid tumors as an effective drug treatment; hence, mice bearing tumors treated with the DoxMetOx therapy showed a complete inhibition of the tumor mass growing in 15 days of treatment depicted by the micro PET images. In vitro studies displayed that the three drugs together act by inhibiting both, mTOR-phosphorylation and expression of LDH-A gene, promoting apoptosis via dependent on the caspase-3 pathway, accompanied by cleavage of PARP. Moreover, induction of autophagy process was observed by the accumulation of LC3-II, a primordial protein implicated in the conformation and elongation of the autophagolysosome. Conclusions: The lack of effective drugs to inhibit TNBC growth is the main cause of therapy failure and tumor relapse. We have showed that targeting crucial molecular pathways in cancer by the combination of Doxorubicin, Metformin, and Oxamate resulted as an efficient and rapid tumor growth inhibitor in a triple negative xenograft model. Our findings are promising for patients diagnosed with TNBC tumors, for which unfortunately there are no reliable drug therapies.

Structural and functional characterization of DUF1471 domains of Salmonella proteins SrfN, YdgH/SssB, and YahO.

Bacterial species in the Enterobacteriaceae typically contain multiple paralogues of a small domain of unknown function (DUF1471) from a family of conserved proteins also known as YhcN or BhsA/McbA. Proteins containing DUF1471 may have a single or three copies of this domain. Representatives of this family have been demonstrated to play roles in several cellular processes including stress response, biofilm formation, and pathogenesis. We have conducted NMR and X-ray crystallographic studies of four DUF1471 domains from Salmonella representing three different paralogous DUF1471 subfamilies: SrfN, YahO, and SssB/YdgH (two of its three DUF1471 domains: the N-terminal domain I (residues 21-91), and the C-terminal domain III (residues 244-314)). Notably, SrfN has been shown to have a role in intracellular infection by Salmonella Typhimurium. These domains share less than 35% pairwise sequence identity. Structures of all four domains show a mixed α+ß fold that is most similar to that of bacterial lipoprotein RcsF. However, all four DUF1471 sequences lack the redox sensitive cysteine residues essential for RcsF activity in a phospho-relay pathway, suggesting that DUF1471 domains perform a different function(s). SrfN forms a dimer in contrast to YahO and SssB domains I and III, which are monomers in solution. A putative binding site for oxyanions such as phosphate and sulfate was identified in SrfN, and an interaction between the SrfN dimer and sulfated polysaccharides was demonstrated, suggesting a direct role for this DUF1471 domain at the host-pathogen interface.

Colonización por Streptococos B en pacientes con 35-40 semanas de gestación HEODRA- León 2005 / Colonization for Streptococci B in patient with 35-40 weeks of gestation HEODRA - León 2005

En el presente estudio se encontró una prevalencia de Strepcoccus del grupo B del 16.2 porciento, valor que se encuentra dentre los rangos reportados a nivel mundal 5 al 40 porciento).Esta prevalencia pareciera ser baja si se compara al 26.6 porciento reportado por un estudio conducido en el mismo hospital en 2004. Los resultados reflejan que el 69.7 porciento de la población estudiada y el 75.72 porciento de las pacientes con cultivos pisitivos tenían edad entre 20 y 35 años. La mayoría de los pacientes con resultados positivos para Streptococcus del grupo B (grupo colonizado), habían tenido 1-3 embarazos. En cuanto a procesos patológicos asociados se encontró alta frecuencia de leucorrea en ambos grupos (pacientes colonizadas y altamente colonizadas) De acuerdo a la literatura la mayor parte de leucorreas tienen un origen polimicrobiano y entre los microorganismos más frecuentes se encuentra la Chlamydia Trachomatis. Otro proceso patológico asociado a infección por Streptococcus del grupo B en mujeres embarazadas son las infecciones de transmisión sexual que se encontraron casi en la mitad de las pacientes altamente colonizadas (43 porciento) otro proceso patológico es la ruptura prematura de membranas ovulares en el estudio solamente una mujer colonizadas tuvo RPM. En este estudio se encontró que aproximadamente 3/4 de las pacientes iniciaron su vida sexual precoz. De los resultados obtenidos se constata que hasta el momento ninguna de las cepas de SGB estudiadas mostró resistencia a Beta-lactámicos, por lo tanto estos siguen siendo los antibioticos de elección el la profilaxis antibiótica intraparto de las mujeres colonizadas por SGB

Preparation of (166)Dy/(166)Ho-EDTMP: a potential in vivo generator system for bone marrow ablation.

BACKGROUND AND AIM: Bone-seeking radiopharmaceuticals have been proposed for delivering ablative radiation doses to marrow in multiple myeloma and other haematological malignancies. The aim of this research was to examine the feasibility of labelling ethylenediaminetetramethylenephosphonate (EDTMP) with Dy/Ho as an in vivo generator system and to evaluate whether the in vitro and in vivo stability of Dy-EDTMP and Ho-EDTMP complexes is maintained when the daughter Ho is formed. METHODS: Dy was obtained by neutron irradiation of enriched Dy2O3 in a TRIGA Mark III reactor. Labelling was carried out in an aqueous phosphate medium at pH 8.0 by addition of DyCl3 to EDTMP at a molar ratio 1:1.75. Dy/Ho labelled EDTMP was obtained with a 99.3+/-0.6% radiochemical purity determined by thin-layer chromatography and high-performance liquid chromatography. RESULTS: In vitro studies demonstrated that Dy/Ho-EDTMP is unstable after dilution in saline and stable in human serum and no translocation of the daughter nucleus occurring subsequent to beta decay of Dy which could produce release of Ho. Biodistribution in mice shows a fast blood clearance after administration of Dy/Ho-EDTMP with a skeletal uptake of 22.32+/-1.86% ID/g at 2 h and 20.12+/-1.94% ID/g after 10 d, a rapid renal elimination and no accumulation in other organs. Theoretical bone marrow absorbed dose calculations indicate that the Dy/Ho-EDTMP in vivo generator system would produce 7.80 times more radiation dose to marrow than that produced by Sm-EDTMP and 3.47 times more than Ho-DOTMP per unit of initial activity retained in the skeleton. CONCLUSION: The prepared radiolabelled EDTMP has adequate properties as a stable in vivo generator system for bone marrow ablation.