Sexual health and needs for sexology care in digestive cancer patients undergoing chemotherapy: a 4-month cross-sectional study in a French University Hospital.

PURPOSE: To assess sexual health and needs for sexology care of cancer patients during chemotherapy. METHODS: We performed a 4-month cross-sectional study in cancer patients treated by chemotherapy in the digestive cancer department of a regional university hospital. Patients were asked to fill out a self-administered questionnaire about their sexual health, Sexual Quality of Life Questionnaire for Male (SQoL-M) or Female (SQoL-F), and their needs for sexology care. RESULTS: The study sample was composed of 47 men and 31 women. Tumor locations were 36 colorectal (46%), 23 pancreatic (30%), and 19 other digestive cancers (24%). SQoL scores were lower in women (p < .001), in pancreatic and colorectal tumors (p = .041 and p = .033, respectively) compared to other digestive cancers, and in less-educated patients (p = .023). During chemotherapy, 40% of sexually active patients had less frequent sexual intercourse than before diagnosis, and 33% had completely stopped sexual activity. Sexuality care was desired by 44% of respondents. Among them, 83% favored a consultation with a medical sexologist and 63% with a psycho-sexologist, 54% wanted couple therapy, and 31% considered support groups. Patients with colorectal cancer had more frequent sexual intercourse without penetration at the time of survey (p = .036) and more often wanted couple therapy than patients with pancreatic cancer (p = .048). CONCLUSIONS: This study is the first determination of sexual health and sexual quality of life in digestive cancers. Targets for interventions during chemotherapy for digestive cancers include populations with lower sexual quality of life: women, pancreatic sites, patients with sexual troubles during chemotherapy, and less-educated patients.

Prognostic value of baseline seric Syndecan-1 in initially unresectable metastatic colorectal cancer patients: a simple biological score.

In first-line metastatic colorectal cancer (mCRC), baseline prognostic factors allowing death risk and treatment strategy stratification are lacking. Syndecan-1 (CD138) soluble form was never described as a prognostic biomarker in mCRC. We investigated its additional prognostic value for overall survival (OS). mCRC patients with unresectable disease at diagnosis were treated with bevacizumab-based chemotherapy in two independent prospective clinical trials (development set: n = 126, validation set: n = 51, study NCT00489697 and study NCT00544011, respectively). Serums were collected at baseline for CD138 measurement. OS determinants were assessed and, based on the final multivariate model, a prognostic score was proposed. Two independent OS prognostic factors were identified: Lactate Dehydrogenase (LDH) high level (p = 0.0066) and log-CD138 high level (p = 0.0190). The determination of CD138 binary information (cutoff: 75 ng/mL) allowed the assessment of a biological prognostic score with CD138 and LDH values, identifying three risk groups for death (median OS= 38.9, 30.1 and 19.8 months for the low, intermediate and high risk groups, respectively; p < 0.0001). This score had a good discrimination ability (C-index = 0.63). These results were externally confirmed in the validation set. Our study provides robust evidence in favor of the additional baseline soluble CD138 prognostic value for OS, in mCRC patients. A simple biological scoring system is proposed including LDH and CD138 binary status values.

Distinct beta-clamp interactions govern the activities of the Y family PolIV DNA polymerase.

The prototypic Y family DNA polymerase IV (PolIV) of Escherichia coli is involved in multiple replication-associated processes including spontaneous mutagenesis, translesion synthesis (TLS), cell fitness, survival under stressful conditions and checkpoint like functions. It interacts physically and functionally with the replisome's beta processivity clamp through the canonical PolIV C-terminal peptide (CTP). A second interaction that involves a portion of the little finger (LF) domain of PolIV has been structurally described. Here we show that the LF-beta interaction stabilizes the clamp-polymerase complex in vitro and is necessary for the access of PolIV to ongoing replication forks in vivo. However, in contrast to the CTP-beta, the LF-beta interaction is dispensable for the role of the polymerase in TLS. This discloses two independent modes of action for PolIV and, in turn, uncovers a novel way by which the cell may regulate the potentially deleterious effect of such low fidelity polymerases during replication.

The processivity factor beta controls DNA polymerase IV traffic during spontaneous mutagenesis and translesion synthesis in vivo.

The dinB-encoded DNA polymerase IV (Pol IV) belongs to the recently identified Y-family of DNA polymerases. Like other members of this family, Pol IV is involved in translesion synthesis and mutagenesis. Here, we show that the C-terminal five amino acids of Pol IV are essential in targeting it to the beta-clamp, the processivity factor of the replicative DNA polymerase (Pol III) of Escherichia coli. In vivo, the disruption of this interaction obliterates the function of Pol IV in both spontaneous and induced mutagenesis. These results point to the pivotal role of the processivity clamp during DNA polymerase trafficking in the vicinity of damaged-template DNA.

Genetics of mutagenesis in E. coli: various combinations of translesion polymerases (Pol II, IV and V) deal with lesion/sequence context diversity.

The biochemistry and genetics of translesion synthesis (TLS) and, as a consequence, of mutagenesis has recently received much attention in view of the discovery of novel DNA polymerases, most of which belong to the Y family. These distributive and low fidelity enzymes assist the progression of the high fidelity replication complex in the bypass of DNA lesions that normally hinder its progression. The present paper extends our previous observation that in Escherichia coli all three SOS-inducible DNA polymerases (Pol II, IV and V) are involved in TLS and mutagenesis. The genetic control of frameshift mutation pathways induced by N-2-acetylaminofluorene (AAF) adducts or by oxidative lesions induced by methylene blue and visible light is investigated. The data show various examples of mutation pathways with an absolute requirement for a specific combination of DNA polymerases and, in contrast, other examples where two DNA polymerases exhibit functional redundancy within the same pathway. We suggest that cells respond to the challenge of replicating DNA templates potentially containing a large diversity of DNA lesions by using a pool of accessory DNA polymerases with relaxed specificities that assist the high fidelity replicase.