"I Lost My Gift to Him": The Consequences of Female Sexual Dysfunction on Breast Cancer Survivors in Malaysia.

Sexuality is currently neglected in the medical care of cancer patients although female sexual dysfunction (FSD) and sexual problems are highly prevalent among breast cancer patients in Malaysia. This paper explores the consequences of breast cancer and its treatment on the sexuality and sexual health of women with breast cancer using a qualitative design and a phenomenological methodology. Fourteen married women with breast cancer who fulfill the criteria for FSD from Kelantan, Malaysia participated in two interviews: in-depth interview and followed by photo-elicitation interview after two weeks duration. The interviews were audio-recorded, transcribed verbatim, and analyzed using thematic analysis. We identified overlapping themes that can be explained by sexual script theory. Breast cancer treatments disturb the sex response cycle, leading to changes in sexuality, from intimacy in marriage to women preferring physical affection to intercourse. The women struggled with a perceived imperfection about symbol of femininity after noticing changes in their husbands' sexual performance and after experiencing their own sentiments of inadequacy as a wife. Fear and guilt surfaced as part of the journey, accompanied by frustration on the part of the spouse, or him becoming more attentive. This study highlights the problem of breast cancer and its treatment as regards the sexual well-being of patients and their spouses. Hence, recognizing and addressing sexual health will improve the overall experience for survivors.

Coping Strategies for Sexual Problems and Sexual Dysfunction Amongst Malay Women With Breast Cancer. A Qualitative Study.

INTRODUCTION: Women' sexuality becomes complex after breast cancer diagnosis and sexual health is highly neglected in the management of the illness. AIMS: To explore the coping and strategies to overcome sexuality problems and sexual dysfunction among women with breast cancer. MATERIAL AND METHODS: Using the in-depth and photo-elicitation interview methods, this qualitative study following phenomenological analysis was conducted on fourteen married female respondents with breast cancer and had the positive result for female sexual dysfunction (FSD) screened by Female Sexual Function Index (FSFI-6 items) from Kelantan, Malaysia. The interviews data were audio-recorded, transcribed verbatim and managed in analytic computer software NVivo11 Pro. The transcriptions were analyzed using thematic analysis by referring to the meaning-making theory. MAIN OUTCOME MEASURES: We identified overlapping themes of coping and strategies among women with breast cancer to overcome sexual problems and sexual dysfunction which correspond with meaning-making theory. RESULTS: Three themes have emerged. Women with breast cancer that developed sexuality problem and sexual dysfunction strived to accept the illness using religious belief and conform by altering sexual practices. These individuals positively look for a solution by seeking formal healthcare advice, modify their physical appearance, active discussion with the husband and support from other survivors. A few of them passively struggle with the subject by averting the intimacy and receptive toward polygamy. CONCLUSION: This study highlighted the various mechanisms that emphasized the pivotal role of religious belief and relationship context as key factors in the coping strategies among women with breast cancer in Malaysia. The finding may not be generalized to other countries. Che Ya SN, Muhamad R, Zain NM, et al. Coping Strategies for Sexual Problems and Sexual Dysfunction Amongst Malay Women With Breast Cancer. A Qualitative Study. Sex Med 2021;9:100336.

LASSO­based Cox­PH model identifies an 11­lncRNA signature for prognosis prediction in gastric cancer.

The present study aimed to identify a long non­coding (lnc) RNAs­based signature for prognosis assessment in gastric cancer (GC) patients. By integrating gene expression data of GC and normal samples from the National Center for Biotechnology Information Gene Expression Omnibus, the EBI ArrayExpress and The Cancer Genome Atlas (TCGA) repositories, the common RNAs in Genomic Spatial Event (GSE) 65801, GSE29998, E­MTAB­1338, and TCGA set were screened and used to construct a weighted correlation network analysis (WGCNA) network for mining GC­related modules. Consensus differentially expressed RNAs (DERs) between GC and normal samples in the four datasets were screened using the MetaDE method. From the overlapped lncRNAs shared by preserved WGCNA modules and the consensus DERs, an lncRNAs signature was obtained using L1­penalized (lasso) Cox­proportional hazard (PH) model. LncRNA­mRNA networks were constructed for these signature lncRNAs, followed by functional annotation. A total of 14,824 common mRNAs and 2,869 common lncRNAs were identified in the 4 sets and 5 GC­associated WGCNA modules were preserved across all sets. MetaDE method identified 1,121 consensus DERs. A total of 50 lncRNAs were shared by preserved WGCNA modules and the consensus DERs. Subsequently, an 11­lncRNA signature was identified by LASSO­based Cox­PH model. The lncRNAs signature­based risk score could divide patients into 2 risk groups with significantly different overall survival and recurrence­free survival times. The predictive capability of this signature was verified in an independent set. These signature lncRNAs were implicated in several biological processes and pathways associated with the immune response, the inflammatory response and cell cycle control. The present study identified an 11­lncRNA signature that could predict the survival rate for GC.

The C3G/Rap1 pathway promotes secretion of MMP-2 and MMP-9 and is involved in serous ovarian cancer metastasis.

Complete resection is pivotal to improve survival to epithelial ovarian cancer (EOC). Crk SH3-domain-binding guanine nucleotide-releasing factor (C3G) is involved in multiple signaling pathways and it has opposite roles in different cancers. The present study aimed to identify C3G expression in ovarian tissue samples from patients with EOC and to explore its association with tumor grade. Eighty-seven archival paraffin-embedded, formalin-fixed, ovarian cancer tissues with serous histology were stained for C3G by immunohistochemistry. To evaluate the contribution of C3G to Rap1 activity, 36 patients with serous ovarian cancer (SOC) were investigated. Additionally, C3G was knocked down in SKOV3 and HEY cells. C3G regulated Rap1 activity and high Rap1 activity was correlated with poor differentiation, advanced FIGO stage, and unsuccessful cytoreductive surgery of SOC. Knockdown of C3G suppressed cell invasion, intravasation and extravasation, and reduced Rap1 activity and secretion of matrix metalloproteinase (MMP)-2 and MMP-9. C3G-mediated activation of Rap1 could direct the tumor pattern of human SOC by promoting the secretion of MMP-2 and MMP-9. These results suggest that C3G is involved in the metastatic spread of EOC.

Elmo1 helps dock180 to regulate Rac1 activity and cell migration of ovarian cancer.

OBJECTIVE: Engulfment and cell motility 1 (Elmo1) has been reported to cooperate with dedicator of cytokinesis 1 (Dock180) and to be linked to the invasive phenotype of cancer cells through activating small G-protein Rac. We aimed to study the role of Elmo1 in the malignant migration of ovarian cancer. METHODS: Engulfment and cell motility 1 expression was evaluated in specimens from 93 patients with serous ovarian cancer (SOC) by immunohistochemical staining. Next, Elmo1-RNAi cells were established by validated small interference RNAs. Cell proliferation and cell motility were observed and compared with Dock180-RNAi cells. To confirm their synergetic contribution to forming focal adhesion and activating Rac1, Rac1-GTP level was measured by GST pull-down assay and immunofluorescence was used to observe focal adhesion formation both in Elmo1-RNAi and Dock180-RNAi cells. RESULTS: Engulfment and cell motility 1 was mainly overexpressed in high-grade SOC tissues. Western blot analysis demonstrated that both Elmo1 and Dock180 expressions were hampered in Elmo1-RNAi cells. Compared with the negative control, decreased colony formation and cell invasion were observed in Elmo1-RNAi cells and Dock180-RNAi cells. Consistently, both exhibited reduced Rac1-GTP level and inhibited focal adhesion formation. CONCLUSIONS: Engulfment and cell motility 1 presents with synergetic action in helping Dock180 to activate Rac1 and promote cell motility, and thus promote untoward expansion and aggressiveness of SOC.

Crk and CrkL present with different expression and significance in epithelial ovarian carcinoma.

Adaptor protein Crk and CrkL were thought to be closely related because both consist of one SH2 and two SH3 domains and share 60% homology with the highest identity within their functional domains. Their functions were most presumed to be in part, if not all, redundant. And both were suggested to be implicated in carcinogenesis. In this study, both Crk and CrkL presented with much higher expression in ovarian cancer tissues than those in normal and benign ovarian tissues. However, in contrast with CrkL, high Crk expression displayed close association with advanced stages and high-grade diseases. Furthermore, the differential binding selectivity of Crk and CrkL to their downstream partners Dock 180 and C3G was demonstrated in ovarian cancer cell line SKOV3 through coimmunoprecipitation. Additionally, Crk-knockdown cells presented with changed morphology, reduced growth, and cell invasion but remained viable. In contrast, all CrkL-knockdown cells could not survive over time, gradually detaching from the bottom of plastic dish. In conclusion, these two highly homologous proteins hold features that allow for the differential association with each binding molecules, thereby activating different signaling pathways and being involved in diverse roles in ovarian cancer.

The role of Crk/Dock180/Rac1 pathway in the malignant behavior of human ovarian cancer cell SKOV3.

Small GTPases, particularly the Rho family, are key regulators of cell motility and migration. Dock180 was well known for the main target of signal adaptor protein Crk and acted as a guanine-nucleotide exchange factor for small GTPase Rac1. In the present study, Dock180 was found to combine primarily with CrkI other than CrkII, and its association with Elmo1 was also demonstrated in ovarian cancer cell SKOV3. To evaluate the role of Dock180 in human ovarian cancer cell, we performed RNAi-mediated knockdown of Dock180 in SKOV3 cells using small interfering RNA expression vector. In Dock180 knockdown cells, we found that Elmo1 expression and Rac1 activity were decreased simultaneously. By contrast, the expressions of both another Crk-combining molecule C3G and Rap1 activity were observed to increase obviously. Accordingly, all Dock180 knockdown cells present with evident change in cell morphology, reduced cell proliferation, and attenuated cell migration. Taken together, these results suggest that signal transfer of Crk/Dock180/Rac1 is implicated in actin cytoskeleton reorganization and thus in the cell proliferation, motility, invasion, and of human ovarian cancer cell line SKOV3.

Correlation between deoxyribonucleic acid loads of human papillomavirus and recurrence of condylomata acuminata.

To determine the correlation between deoxyribonucleic acid (DNA) loads of human papillomavirus (HPV) and recurrence of condylomata acuminata (CA), 31 cases of primary CA and 32 cases of recurrent CA were assayed for the HPV6/11 and HPV16/18 DNA loads by real-time fluorogenic quantitative PCR. The results showed 62 of the 63 cases were HPV6/11 DNA positive (98.4%). The ranges of HPV6/11 DNA contained in primary and recurrent CA were 1.4 x 10(3)-6.7 x 10(7) and 1.2 x 10(4)-3.6 x 10(8) copies/mL, respectively. Of the 62 cases which were HPV6/11 DNA positive, seven cases were also HPV16/18 DNA positive (11.3%). The ranges of HPV16/18 DNA levels in primary and recurrent CA were 1.9 x 10(3)-1.6 x 10(4) and 1.4 x 10(5)-1.7 x 10(7) copies/mL, respectively . The HPV6/11 and HPV16/18 DNA loads in recurrent CA were statistically higher than that found in primary CA (P = 0.041 and 0.023, respectively). The DNA loads of HPV6/11 were correlated with the duration, extent of the disease and frequency of recurrence. There is a significant correlation between loads of HPV DNA and recurrence of CA. These findings have important implications for the treatment of CA.

[Correlation between DNA load of human papillomavirus and recurrence of condyloma acuminata].

OBJECTIVE: To determine the correlation between DNA load of human papillomavirus (HPV) and recurrence of condyloma acuminata (CA). METHODS: The HPV6/11 and HPV16/18 DNA load of 31 cases of primary CA and 32 cases of recurrent CA were detected by real-time fluorogenic quantitative PCR. RESULTS: Among the 63 CA patients, 62 cases were HPV6/11 DNA positive. The positive rate was 98.4%. The ranges of HPV6/11 DNA load in primary and recurrent CA were 1.4x10(3)-6.7x10(7) copies/ml and 1.2x10(4)-3.6x10(8) copies/ml respectively. Of 62 cases with HPV6/11 DNA positive, 7 cases were HPV16/18 DNA positive (11.3%). The ranges of HPV16/18 DNA load in primary and recurrent CA were 1.9x10(3)-1.6x10(4) copies/ml and 1.4x10(5)-1.7x10(7) copies/ml respectively. The HPV6/11 and HPV16/18 DNA load in recurrent CA were higher than in primary CA (P < 0.05). The DNA load of HPV6/11 was positively correlated with times of recurrence and course of disease (r=0.37 and 0.30 respectively). CONCLUSION: Certain correlation exists between DNA load of HPV and recurrence of CA.