Investigation of EGFR/pi3k/Akt signaling pathway in seminomas.

Activation of the receptor for epidermal growth factor (EGFR) in some testicular tumors activates several signaling pathways. Some components of these pathways are phosphorylated or mutated in testicular germ tumors (TCGT), including EGFR, Kirstein ras oncogen (KRAS) and cell surface protein of the germ cell (KIT). The latter two activate RAF /MEK/ERK and PI3 K/AKT, and interconnect with the EGFR/pI3 k/Akt pathway. We investigated the expression of EGFR/pI3 k/Akt pathway proteins in seminomas and in their precursor lesion, germinal cell neoplasia in situ (GCNIS) and related genetic mutations. We used immunohistochemistry for pEGFR, pI3 k and pAkt expression with a scoring system for 46 seminoma surgical specimens: 36 classical and 10 GCNIS. In 17 samples, the mutations of EGFR (exons 19 - 21), KIT (exons 11, 17) and KRAS (exons 2, 3) were investigated using qPCR and sequencing. Of the 36 seminomas studied, 22 (61%) expressed pEGFR. Ten samples exhibited high scores for pEGFR, pI3 k and pAkt. In 5 of 17 cases (33%) some mutation was exhibited in the exons studied: 21 of EGFR (2), 17 of EGFR (1), 3 of KRAS (1) and 11 of KIT (1). Six cases exhibited nuclear translocation of EGFR; of these, four exhibited mutations of EGFR, KRAS and KIT. Eight of ten of the GCNIS expressed a high pEGFR score (80%). In 2 of 6 cases (33%), mutation was detected in exon 21 of EGFR and one smear showed EGFR translocation to the nucleus. The translocation represents a subpopulation with worse prognosis for TCGT. The EGFR/pI3 k/Akt signaling pathway is linked to TDRG1, which regulates chemosensitivity to cisplatin; this is a mechanism of resistance to treatment. TDRG1 and the EGFR/pI3 k/pAkt pathway could be therapeutic targets for seminomas resistant to cisplatin.

Expressions of E2 and E7-HPV16 proteins in pre-malignant and malignant lesions of the uterine cervix.

Continuous production of the E7 protein from different types of high risk human papilloma virus (HPV) is required for progression of malignancy. We developed antibodies against HPV type 16 E7 and E2 proteins to evaluate their utility as markers for diagnosis during early stages of cervical cancer. Forty biopsies from uterine cervices were diagnosed as low grade intraepithelial lesion (LSIL), high grade intraepithelial lesion (HSIL), squamous carcinoma (SC), in situ adenocarcinoma (ISA) and invasive adenocarcinoma (AC), all of which were infected with HPV 16. Immunohistochemistry was used to investigate the expressions of E7 and E2 (both from HPV 16) and p16. P16 was expressed in eight of 12 LSILs, in all HSILs, in 16 of 18 SC and in all ACs. E2 was expressed in six of 12 LSILs. E7 was positive in eight of 12 LSILs and in all HSIL and carcinomas. The expressions of E2 and E7 of HPV16 related to p16 expression confirmed the value of the viral oncogenic proteins as complementary to histology and support the carcinogenic model of the uterine cervix, because HPVDNA integration into cellular DNA implies the destruction of the gene encoding E2, which suppresses the expression of the E6 and E7 oncoproteins. E2 from HPV16 could be marker for LSILs, while E7 could be a marker for progression of LSILs to HSILs in patients infected by HPV16, because viral typing has little positive predictive value.

A six-year experience with anal cytology in women with HPV in the lower genital tract: utility, limitations, and clinical correlation.

This study assessed the utility and limitations of anal cytology as a screening method for women infected with human papilloma virus (HPV) in the lower genital tract. Furthermore, this study aimed to establish risk factors for pathological anal cytology/biopsy findings, the prevalence of anatomopathological lesions associated with positive anal brushings, and the frequency of concomitant lesions of the lower genital tract. A cross-sectional, retrospective, descriptive study in 207 women with HPV-associated lesions of the lower genital tract and 25 women with immunosuppression was carried out. Anal cytology, high resolution anoscopy, and biopsy of suspicious lesions were performed. In total, 232 anal brushings were performed: 184 (79.3%) were negative, 24 (10.34%) showed atypical squamous cells of undeterminated significance, 18 (7.7%) showed low-grade squamous intraepithelial lesions, and 6 (2.6%) showed high-grade squamous intraepithelial lesion. Cytohistological correlation was obtained for 70 cases. The sensitivity of anal cytology in detecting intraepithelial lesions was 70%, whereas the specificity was 93%. The sensitivity of the method for detecting high-grade lesions (84%) was higher, than that for detecting low-grade lesions (66%). The most frequently associated pathology was vulvar lesion. It is important to perform anal brushings in women who have had lower genital tract biopsies for HPV-associated lesions due to the high prevalence of anal lesions in such patients. Anal cytology is useful for detecting high-grade lesions but the sensitivity for detecting low-grade lesions is low. It is of the utmost importance to perform high-resolution anoscopy and biopsy in women with suspicious lesions in order to confirm the pathology.

[The micro-erythrocyte sedimentation rate in the newborn and the infant (author's transl)]. / Microeritrosedimentación en el recién nacido y en el lactante.

A new simple micro-erythrocyte sedimentation rate method in newborns and infants is proposed. The results on 300 determinations are exposed. Results of the classic method and this micro-method for erythrocyte sedimentation rate as far as 20 mm. per hour, may differ in +/- 3.72 in 68.27% and in +/- 7.44 in 95.45% of the cases.

[Endocardial fibroelastosis. Pathologic and clinical findings in 20 cases (author's transl)]. / Firbroelastosis endocárdica Estudio clínico y anatómico de veinte niños

Pathologic and clinical findings in 20 infants with Endocardial Fibroelastosis are reported. Ten cases were considered as secondary Fibroelastosis due to left heart structural anomalies. Purpose was to find some clinical criteria to establish differential diagnosis between primary and secondary forms. QRS voltages in electrocardiogram were higher in primary forms and QRS axis in the frontal plane had more rightward deviation in secondary ones.

[Total anomalous pulmonary venous drainage below the diaphragm. Report of three cases and semiologic considerations (author's transl)]. / Drenaje venoso pulmonar anómalo total infradiafragmático. Consideraciones semiológicas a propósito de tres casos.

Clinical, hemodynamic and pathologic findings of three patients with total anomalous pulmonary venous drainage to the portal vein system are presented. Some of the findings are emphasized because of its rarity in previous reports. These are: 1) Cyanosis was mild. 2) There was some obstruction of the foramen ovale, besides the obstruction at the portal system level. In two patients gastrointestinal bleeding and analitical evidence of renal failure, were found, both findings not previously reported to our knowledge.

A multicenter, double-blind, randomized comparison of oral ondansetron 8 mg b.i.d., 24 mg q.d., and 32 mg q.d. in the prevention of nausea and vomiting associated with highly emetogenic chemotherapy. S3AA3012 Study Group.

The objectives of this study were to compare the efficacy and safety of orally administered ondansetron 8 mg b.i.d., 24 mg q.d., and 32 mg q.d. in the prevention of nausea and vomiting associated with high-dose cisplatin-based chemotherapy (cisplatin > or = 50 mg/m2). This was a randomized, parallel-group, double-blind study conducted in North America. It was planned that all patients would receive one of the following orally administered ondansetron treatments 30 min before starting cisplatin dosing (administered over < or = 3 h): 8 mg b.i.d. with 8 h between doses (124 patients), 24 mg q.d. (116 patients), and 32 mg q.d. (117 patients). Use of prophylactic corticosteroids was not permitted. During the 24-h study period, the highest complete response rate (no emesis, rescue antiemetic therapy, or withdrawal) occurred in patients who received ondansetron 24 mg q.d.: 76/115 or 66%, as against 68/124 (55%) after ondansetron 8 mg b.i.d. and 64/117 (55%) after ondansetron 32 mg q.d. Complete control of nausea (no nausea, no rescue, no withdrawal) occurred in more patients in the ondansetron 24 mg q.d. group (64/114, 56%) than in the ondansetron 8 mg b.i.d. group (43/121, 36%) or in the ondansetron 32 mg group (55/117, 50%). These results demonstrate that following highly emetogenic cisplatin-based chemotherapy (> or =2 50 mg/m2), oral ondansetron 24 mg q.d. is more effective than 8 mg b.i.d. for overall control of nausea, and at least as effective if not more effective in the control of acute vomiting than 8 mg b.i.d. or 32 mg q.d. Ondansetron 24 mg q.d. was well tolerated, and no new or unexpected adverse events were identified.