Mixed Sequence Reader: A Program for Analyzing DNA Sequences with Heterozygous Base Calling

The direct sequencing of PCR products generates heterozygous base-calling fluorescence chromatograms that are useful for identifying single-nucleotide polymorphisms (SNPs), insertion-deletions (indels), short tandem repeats (STRs), and paralogous genes. Indels and STRs can be easily detected using the currently available Indelligent or ShiftDetector programs, which do not search reference sequences. However, the detection of other genomic variants remains a challenge due to the lack of appropriate tools for heterozygous base-calling fluorescence chromatogram data analysis. In this study, we developed a free web-based program, Mixed Sequence Reader (MSR), which can directly analyze heterozygous base-calling fluorescence chromatogram data in .abi file format using comparisons with reference sequences. The heterozygous sequences are identified as two distinct sequences and aligned with reference sequences. Our results showed that MSR may be used to (i) physically locate indel and STR sequences and determine STR copy number by searching NCBI reference sequences; (ii) predict combinations of microsatellite patterns using the Federal Bureau of Investigation Combined DNA Index System (CODIS); (iii) determine human papilloma virus (HPV) genotypes by searching current viral databases in cases of double infections; (iv) estimate the copy number of paralogous genes, such as β-defensin 4 (DEFB4) and its paralog HSPDP3

Molecular imaging in the management of cervical cancer

Positron emission tomography (PET), magnetic resonance imaging (MRI), and integrated 18-fluorodeoxyglucose (18F-FDG) PET/computed tomography are valuable techniques for assessing prognosis, treatment response after the completion of concurrent chemoradiation, suspicious or documented recurrence, unexplained post therapy elevations in tumor markers, and the response to salvage treatment when managing cervical cancer. However, PET plays a limited role in the primary staging of MRI-defined node-negative patients. Currently, 18F-FDG is still the only tracer approved for routine use, but several novel targeting PET compounds, high-Tesla MRI machines, diffusion-weighted imaging without contrast, and dynamic nuclear polarized-enhanced 13C-MR spectroscopic imaging may hold promising applications

Immunotherapy for advanced or relapsed cervical cancer

Cervical cancer is the third most commonly diagnosed cancer and the fourth leading cause of cancer deaths worldwide. Conventional approaches by surgery, radiotherapy, and/or chemotherapy cannot provide satisfied therapeutic outcomes for advanced or relapsed cervical cancer. Thus, immunotherapy or biotherapy for these patients has been the mode of treatment. A number of studies on immunotherapy for cervical cancer in animals has been published. This time, we summarized our experiences and concepts with regard to the therapeutic approach for advanced cervical cancer in humans

Rare Subtype of Endometrial Cancer: Undifferentiated/Dedifferentiated Endometrial Carcinoma, from Genetic Aspects to Clinical Practice

Endometrial cancer (EC) is one of the most common gynecologic cancers worldwide. There were 417,367 newly diagnosed cases and 97,370 deaths due to this disease worldwide in 2020. The incidence rates have increased over time, especially in countries with rapid socioeconomic transitions, and EC has been the most prevalent gynecologic malignancy in Taiwan since 2012. The new EC molecular classifications of The Cancer Genome Atlas (TCGA) Research Network include clear-cell carcinoma, serous carcinoma, and carcinosarcoma, while undifferentiated/dedifferentiated EC (UDEC) is not mentioned, and most previous clinical trials for EC have not included UDEC. UDEC is rare, has an aggressive growth pattern, tends to be diagnosed at an advanced stage, and is resistant to conventional chemotherapy. In this review, case series or case reports on the clinical features and genomic/epigenetic and expression profiles on UDEC data are summarized in order to identify potential molecular targets for current and future research

Immune Tolerance of Embryo Implantation and Pregnancy: The Role of Human Decidual Stromal Cell- and Embryonic-Derived Extracellular Vesicles

Embryo–endometrial communication plays a critical role in embryo implantation and the establishment of a successful pregnancy. Successful pregnancy outcomes involve maternal immune modulation during embryo implantation. The endometrium is usually primed and immunomodulated by steroid hormones and embryo signals for subsequent embryo implantation and the maintenance of pregnancy. The roles of extracellular vesicles (EVs) and microRNAs for the embryo–maternal interactions have been elucidated recently. New evidence shows that endometrial EVs and trophectoderm-originated EV cargo, including microRNAs, proteins, and lipids in the physiological microenvironment, regulate maternal immunomodulation for embryo implantation and subsequent pregnancy. On the other hand, trophoblast-derived EVs also control the cross-communication between the trophoblasts and immune cells. The exploration of EV functions and mechanisms in the processes of embryo implantation and pregnancy will shed light on a practical tool for the diagnostic or therapeutic approaches to reproductive medicine and infertility

Rare Subtype of Endometrial Cancer: Undifferentiated/Dedifferentiated Endometrial Carcinoma, from Genetic Aspects to Clinical Practice

Endometrial cancer (EC) is one of the most common gynecologic cancers worldwide. There were 417,367 newly diagnosed cases and 97,370 deaths due to this disease worldwide in 2020. The incidence rates have increased over time, especially in countries with rapid socioeconomic transitions, and EC has been the most prevalent gynecologic malignancy in Taiwan since 2012. The new EC molecular classifications of The Cancer Genome Atlas (TCGA) Research Network include clear-cell carcinoma, serous carcinoma, and carcinosarcoma, while undifferentiated/dedifferentiated EC (UDEC) is not mentioned, and most previous clinical trials for EC have not included UDEC. UDEC is rare, has an aggressive growth pattern, tends to be diagnosed at an advanced stage, and is resistant to conventional chemotherapy. In this review, case series or case reports on the clinical features and genomic/epigenetic and expression profiles on UDEC data are summarized in order to identify potential molecular targets for current and future research

Small cell neuroendocrine carcinoma of the cervix: From molecular basis to therapeutic advances

Small cell neuroendocrine carcinoma of the cervix (SCNECC) is an uncommon but aggressive uterine malignancy, the cause of which is generally associated with human papillomavirus (HPV) infection. A lack of clinical trials and evidence-based treatment guidelines poses therapeutic challenges to this rare tumor. At present, published data remain limited to case series and case reports. While clinical management has traditionally followed those of small cell neuroendocrine (SCNE) lung cancer relying on surgery, chemoradiation, and systemic chemotherapy, the prognosis remains dismal. Immune checkpoint inhibitors (ICIs), such as monoclonal antibodies that target programmed death-1 (PD-1) or programmed death-ligand 1 (PD-L1), atezolizumab and durvalumab have proven effective in extensive-stage SCNE lung cancer. Moreover, pembrolizumab has also proven beneficial effects when added onto chemotherapy in metastatic and recurrent HPV-associated non-SCNE cervical cancer. It holds promise to use ICIs in combination with chemoradiation to improve the clinical outcomes of patients with SCNECC. Future advances in our understanding of SCNECC biology – associated with the study of its genomic and molecular aberrations as well as knowledge from SCNE of lung and other extrapulmonary sites– would be helpful in discovering new molecular targets for drug development. Collaborative efforts and establishment of a SCNECC-specific biobank will be essential to achieve this goal