Mitochondrial caseinolytic protease p: A possible novel prognostic marker and therapeutic target in cancer

Caseinolytic protease P (ClpP) is a mitochondrial serine protease. In mammalian cells, the heterodimerization of ClpP and its AAA+ ClpX chaperone results in a complex called ClpXP, which has a relevant role in protein homeostasis and in maintaining mitochondrial functionality through the degradation of mitochondrial misfolded or damaged proteins. Recent studies demonstrate that ClpP is upregulated in primary and metastatic human tumors, supports tumor cell proliferation, and its overexpression desensitizes cells to cisplatin. Interestingly, small modulators of ClpP activity, both activators and inhibitors, are able to impair oxidative phosphorylation in cancer cells and to induce apoptosis. This review provides an overview of the role of ClpP in regulating mitochondrial functionality, in supporting tumor cell proliferation and cisplatin resistance; finally, we discuss whether this protease could represent a new prognostic marker and therapeutic target for the treatment of cancer

Primary Vaginal Carcinoma Arising on Cystocele Mimicking Vulvar Cancer

Background: Primary vaginal carcinoma is a rare gynaecological tumour representing 1%–3% of all gynaecologic cancers. Several studies report increased vaginal cancer risk associated with genital prolapse following the occurrence of inflammatory lesions or decubitus ulcers. Case: We report the rare case of an 82-year-old woman with primary squamous cell carcinoma arising from vaginal wall prolapse. Vaginal carcinoma was suspected during gynaecological examination for vulvar bleeding. A wide local excision was performed and pathologic examination revealed a primary squamous cell carcinoma of the vagina. Conclusion: Persistent genital prolapse may be at risk for vaginal carcinoma, and cytological and a colposcopic assessments are essential to identify patients who require diagnostic biopsy

Germinal ovarian tumors in reproductive age women: Fertility-sparing and outcome

MOGCTs (malignant ovarian germ cell tumors) are rare tumors that mainly affect patients of reproductive age. The aim of this study was to evaluate the fertility and survival outcomes in young women with MOCGTs treated with fertility-sparing surgery (FSS).From 2000 to 2018, data from 28 patients of reproductive age with a diagnosis of MOGCT at the University of Bari were collected. Most received FSS, and in patients treated conservatively, the reproductive outcome and survival were investigated. Data of patient demographics, clinical presentation, oncology marker dosage, staging, type of surgery, histological examination, survival, and reproductive outcome were collected from hospital and office charts. All informed consent was obtained from all patients. The median age was 24 (range: 9-45 years). The majority of the patients had stage IIIC. Twenty-four woman received FSS consisting of unilateral ovariectomy and omentectomy, whereas only 4 women, based on their stage (IIIC), received a radical surgery (hysterectomy with bilateral adnexectomy, lymphadenectomy, and omentectomy). Our study shows that FSS in MOGCTs can produce good results both on reproductive outcomes and on survival. Indeed, in our group, there was only 1 case of exitus as result of recurrence. Furthermore, patients after FSS maintained normal ovarian function and 5 of 5 women who tried to get pregnant succeeded spontaneously. The median follow-up was 90 months (range 3-159).Conservative surgery for MOGCTs should be considered for women of reproductive age who wish to preserve fertility

Therapeutic challenges for cisplatin-resistant ovarian germ cell tumors

The majority of patients with advanced ovarian germ cell cancer are treated by cisplatin-based chemotherapy. Despite adequate first-line treatment, nearly one third of patients relapse and almost half develop cisplatin-resistant disease, which is often fatal. The treatment of cisplatin-resistant disease is challenging and prognosis remains poor. There are limited data on the efficacy of specific chemotherapeutic regimens, high-dose chemotherapy with autologous progenitor cell support and targeted therapies. The inclusion of patients in clinical trials is strongly recommended, especially in clinical trials on the most frequent male germ cell tumors, to offer wider therapeutic opportunities. Here, we provide an overview of current and potential new treatment options including combination chemotherapy, high-dose chemotherapy and molecular targeted therapies, for patients with cisplatin-resistant ovarian germ cell tumors

An analysis on decentralized adaptive MAC protocols for Cognitive Radio networks

The scarcity of bandwidth in the radio spectrum has become more vital since the demand for more and more wireless applications has increased. Most of the spectrum bands have been allocated although many studies have shown that these bands are significantly underutilized most of the time. The problem of unavailability of spectrum and inefficiency in its utilization has been smartly addressed by the Cognitive Radio (CR) Technology which is an opportunistic network that senses the environment, observes the network changes, and then using knowledge gained from the prior interaction with the network, makes intelligent decisions by dynamically adapting their transmission characteristics. In this paper some of the decentralized adaptive MAC protocols for CR networks have been critically analyzed and a novel adaptive MAC protocol for CR networks, DNG-MAC which is decentralized and non-global in nature, has been proposed. The results show the DNG-MAC out performs other CR MAC protocols in terms of time and energy efficiency

Celecoxib for the prevention of nonmuscle invasive bladder cancer: Results from a matched control study

New targets and approaches are under investigation for the treatment of nonmuscle invasive bladder cancer (NMIBC). Preclinical data suggest cyclooxygenase-2 (COX-2) as a promising target. Celecoxib, a COX-2 selective inhibitor, inhibits tumor development and enhances survival, both in vitro and in vivo models of bladder cancer. Therefore, we conducted a pilot study of celecoxib to prevent recurrence in patients with intermediate risk NMIBC

Reproductive outcomes and fertility preservation strategies in women with malignant ovarian germ cell tumors after fertility sparing surgery

Malignant ovarian germ cell tumors are rare tumors that mainly affect patients of reproductive age. The aim of this study was to investigate the reproductive outcomes and fertility preservation strategies in malignant ovarian germ cell tumors after fertility-sparing surgery. Data in literature support that fertility-sparing surgery is associated with an excellent oncological outcome not only in early stages malignant ovarian germ cell tumors but also in advanced stages. Moreover, the possibility of performing conservative treatment should be considered even in case of relapse or advanced disease, given the high chemosensitivity. Indeed, available data have shown that menstrual function is maintained after platinum-based regimens in over 85–95% of patients with malignant ovarian germ cell tumors and rate of premature menopause reported in literature ranges between 3% and 7.4%, while premature ovarian failure rates are between 3.4% and 5%. Moreover, reproductive outcomes are about 80% with no increase in the risk of teratogenicity compared to general population. Therefore, conservative surgery for malignant ovarian germ cell tumors currently may represent a therapeutic option in patients who wish to preserve fertility but must be available for extended follow-up and after subscribing to informed consent

The role of ultrasound guided sampling procedures in the diagnosis of pelvic masses: A narrative review of the literature

Ultrasound-guided sampling methods are usually minimally invasive techniques applied to obtain cytological specimens or tissue samples, mainly used for the diagnosis of different types of tumors. The main benefits of ultrasound guidance is its availability. It offers high flexibility in the choice of sampling approach (transabdominal, transvaginal, and transrectal) and short duration of procedure. Ultrasound guided sampling of pelvic masses represents the diagnostic method of choice in selected patients. We carried out a narrative review of literatures regarding the ultrasound-guided methods of cytological and histological evaluation of pelvic masses as well as the positive and negative predictors for the achievement of an adequate sample

Coexistence of an imbalance of cytokines, chemokines and growth factors serum levels and symptoms of fatigue and pain in long-term breast cancer survivors.

Background: Fatigue, pain and depression are common problems among long-term cancer survivors (BCS) which in some patients may persist for many years after healing and the completion of treatment. Several studies have reported that increased serum levels of chemokines and growth factors are particularly significantly correlated with the coexistence of these disorders in cancer survivors. The aim of this study was to assess whether the altered imbalance of pro-inflammatory cytokines, growth factors and chemokine serum levels are associated to presence of fatigue and pain in long-term breast cancer survivors . Methods: Ninety-three BCS were enrolled in this study and blood samples taken from each. Serum levels of 25 analytes including cytokines, growth factors and chemokines were tested by enzyme immunoassay using the flexible Bio-Plex System. Participants also completed a questionnaire measuring demographic, clinical and behavioral variables. Results: Non-parametric discriminant analysis showed that fatigued BCS had significantly higher serum levels of FGF and lower IL-4 and IL-8 compared to the non-fatigued group, while BCS with pain had an increase in eotaxin serum levels and lower IL-4 and Il-7 compared to the group without pain. Univariate analysis showed a statistically significant difference in both mental and physical qol, with levels lower in the subgroup who presented pain than in those without: p = 0.0003 and p < 0.0001 respectively. A lower value of Rantes (p = 0.0131) in breast cancer survivors with pain compared to the group without pain, and a higher median value of TNF-α (p = 0.054) in the pain group than in those without pain was observed. The level of depression was higher than the score of 50 on the Zung scale in fatigued survivors compared to non-fatigued survivors (p = 0.0006). Conclusions: Our results suggest that an altered balance of chemokines, cytokines and growth factors serum levels may be associated to presence of symptoms such as fatigue and pain in breast cancer survivors at an average of 5 years after diagnosis